The anterior cruciate ligament, or ACL, is the strap of connective tissue that keeps the thigh bone from sliding forward over the shin bone. In adults, tears of this ligament are among the most common and consequential sports injuries, and in skeletally immature patients they pose a particular surgical dilemma: standard reconstruction techniques can damage the very growth plates that still have work to do. Understanding what a normal, developing ACL looks like on MRI at every age is therefore not an academic exercise. It is the reference frame against which abnormal anatomy, injury and surgical planning must be judged. Until now, the researchers note, age- and sex-related developmental patterns of the pediatric knee have remained incompletely characterized on routine imaging.

To fill that gap, the team conducted a retrospective single-center study of 520 children and adolescents aged six to eighteen years who had undergone knee MRI. From those scans, the investigators extracted a set of quantitative features: the length of the ACL, the width of the intercondylar notch, the height of the medial femoral epiphysis, abbreviated MEH, and the status of the distal femoral physis, the cartilaginous growth plate near the knee end of the thigh bone. The physis was assessed categorically, reflecting the familiar radiological progression from an entirely open plate, through partial closing, to a fully closed and fused structure. Statistical treatment of the data relied on generalized additive models, which allow flexible, non-linear relationships between age and anatomy to emerge, along with Spearman correlation, Welch analysis of variance and exploratory receiver operating characteristic analyses.

The results trace two parallel but offset developmental timelines. ACL length and intercondylar notch width both increased with age, but the curves flattened earlier in females than in males, a pattern consistent with the earlier onset and completion of skeletal maturation in girls. In other words, by the time boys are still adding length to their ligaments and width to the notch that cradles them, many girls have already reached their adult configuration. This sexual dimorphism matters for anyone interpreting a pediatric knee scan, because a measurement that is perfectly normal for a fourteen-year-old girl might signal delayed development in a boy of the same age. The generalized additive models captured these trajectories as continuous curves rather than abrupt stages, giving clinicians a smoother and more nuanced picture of normal variation.

The distal femoral physis told a complementary story. Its status progressed with age in the expected direction, from open toward closing and closed, and females transitioned earlier toward the closing and closed states. That finding will surprise no pediatric orthopedist, but its value lies in the quantification: the study ties the categorical physeal stages to a large, age-stratified MRI cohort, providing empirical grounding for the visual judgments radiologists make every day. Because the distal femoral physis contributes substantially to leg-length growth, its status is a critical variable in decisions ranging from ligament reconstruction timing to limb-lengthening procedures and the treatment of growth disturbances.

Perhaps the most intriguing contribution of the study is the medial epiphyseal height. This measurement, taken from the medial side of the distal femoral epiphysis, increased steadily with age and, crucially, was significantly associated with physeal status across the entire cohort and separately within each sex. Where the traditional physeal assessment sorts patients into discrete buckets, MEH offers a continuous, quantitative readout of local distal femoral development. The distinction is more than semantic. Continuous measures can track change within a stage, detect subtle deviations from the expected trajectory and potentially refine risk stratification in ways that categorical staging cannot. The authors propose that MEH may complement, rather than replace, the categorical assessment of the distal femoral physis.

The exploratory receiver operating characteristic analysis quantified just how informative that continuous measure might be. An ROC curve plots sensitivity against specificity across all possible cutoffs of a diagnostic test, and the area under that curve, the AUC, summarizes discriminative power on a scale from 0.5, equivalent to a coin flip, to 1.0, perfect classification. For distinguishing physeal status, MEH yielded an AUC of 0.855 in the overall cohort, rising to 0.923 in males and standing at 0.855 in females. Values in this range indicate good to excellent discrimination, suggesting that a single linear measurement already available on routine knee MRI carries substantial information about how far along a child is in the process of skeletal maturation.

Why does this matter beyond the radiology reading room? ACL injuries in children and adolescents are rising as youth sports participation intensifies, and surgeons increasingly face the question of how to reconstruct a torn ligament without injuring a growth plate that still has years of contribution to make to final leg length. Physeal-sparing techniques exist precisely for the skeletally immature, but choosing among them requires an accurate estimate of remaining growth. A continuous, MRI-derived marker such as MEH, correlated with physeal status and characterized across age and sex, could give surgical teams a finer-grained instrument for that estimation, complementing the traditional categorical staging that has long been the standard of care.

The study also carries implications for research into bone development more broadly. The authors frame their findings as a basis for future investigation in skeletally immature patients with ACL injury, and the age- and sex-specific developmental curves they report could serve as normative references in studies of growth disorders, juvenile idiopathic arthritis and other conditions that alter musculoskeletal maturation. Because the measurements come from routine MRI rather than specialized imaging or ionizing radiation, they could in principle be extracted from scans already obtained for clinical reasons, opening the door to large-scale, low-burden normative databases. The researchers acknowledge the exploratory nature of the ROC component, and the retrospective, single-center design means the findings will need validation in independent and more diverse cohorts before they change practice.

Methodological rigor receives attention as well. The team evaluated measurement reliability using intraclass correlation coefficients, a standard gauge of how consistently different observers or repeated measurements produce the same values, an essential step for any quantitative metric hoping to enter clinical use. Ethical oversight came from the Institutional Review Board of Hebei Medical University Third Hospital, which approved the retrospective design with a waiver of written informed consent, and the study was conducted according to the ethical standards of the 1964 Declaration of Helsinki. The work was supported by funding from Hebei Province and China’s National Key Research and Development Program. For now, the study’s legacy may be conceptual as much as practical: it demonstrates that the growing knee can be measured, not merely looked at, and that a single epiphyseal height on an ordinary MRI scan can speak volumes about the hidden timetable of skeletal maturity.

Subject of Research: Age- and sex-related MRI development of the pediatric knee, including ACL morphology, intercondylar notch shape and distal femoral physeal maturation

Article Title: Age- and sex-related MRI developmental patterns of the anterior cruciate ligament, intercondylar notch, and distal femur in children and adolescents

Article References: Age- and sex-related MRI developmental patterns of the anterior cruciate ligament, intercondylar notch, and distal femur in children and adolescents. (n.d.). https://doi.org/10.1186/s12880-026-02876-1

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02876-1

Keywords: anterior cruciate ligament, pediatric knee, MRI, medial epiphyseal height, distal femoral physis, skeletal maturity, intercondylar notch, bone development, sexual dimorphism, musculoskeletal development, growth plate, ACL injury

The research team, led by Yu-hao Li, Zhi-zhao Zhang, Tong Fu, Xiao-bo Liu, Jian-xin Cui, Peng Cheng and Yu-hong Guo, drew on expertise from the National Institute for Communicable Disease Control and Prevention at the Chinese Center for Disease Control and Prevention, the Breeding Research Center of Insect Pests’ Natural Enemies at the Henan Institute of Science and Technology, and the Shandong Institute of Parasitic Diseases. Their goal was explicitly practical: to provide a scientific basis and theoretical support for the formulation of integrated control strategies against a mosquito whose expanding range continues to put hundreds of millions of people at risk of arboviral disease. Understanding how far and how long these insects can travel is a cornerstone of any attempt to predict outbreaks and target interventions.

To capture flight capacity in a controlled and comparable way, the researchers worked with a laboratory strain of Aedes albopictus under strictly standardized environmental conditions, holding temperature, humidity and photoperiod constant throughout the experiments. This was essential because ambient conditions are known to influence insect metabolism and muscle performance, and any uncontrolled variation could have confounded the comparisons between sexes and age classes. Male and female adults were tested at a finely resolved series of ages: every day from one to ten days after emergence, and then again at fifteen, twenty and twenty-five days of age, giving a total of thirteen age points that trace the full arc of adult physiological development.

The central instrument of the study was the flight mill, a classic tethered-flight technique that has been used for decades to quantify the flight potential of insects ranging from moths to beetles to mosquitoes. In a flight mill apparatus, an insect is attached to a lightweight rotating arm and flies in circles; sensors record the number of rotations, which can be converted into cumulative distance, total flight duration and average speed. Because the insect flies against minimal resistance in still air, flight mill measurements do not reproduce the exact aerodynamics of free flight in the field, but they are widely regarded as a robust proxy for an individual’s intrinsic flight capacity, allowing large numbers of insects to be compared under identical conditions.

For each mosquito, the team measured three parameters: cumulative flight distance, cumulative flight duration and average flight speed. These three metrics capture complementary dimensions of flight performance. Distance reflects overall dispersal potential, the quantity most directly relevant to how far a mosquito could carry a virus from one habitat patch to another. Duration reflects endurance, the ability to sustain flight over time, which matters for insects that must traverse hostile or resource-poor landscapes. Average speed reflects the intensity of flight effort and the mechanical power output of the flight muscles. Analyzing all three together gives a far richer picture of flight biology than any single metric alone.

Statistical analysis was carried out with generalized linear models, or GLMs, fitted with a Gamma distribution and a log link function, an approach well suited to strictly positive, right-skewed response variables such as distances and durations. Sex and age were entered as fixed factors, and their interaction, sex multiplied by age, was tested using likelihood ratio tests. This modeling framework allowed the researchers to ask not only whether males and females differ and whether flight changes with age, but also whether the trajectory of age-related change itself differs between the sexes, a subtler question that turns out to be central to the biology of this species.

The results were clear and, in places, striking. For cumulative flight distance, all three effects were significant: age mattered, sex mattered, and the interaction between sex and age mattered as well. Across the sampled ages, females displayed a significantly longer mean cumulative flight distance than males, confirming that the sex responsible for blood feeding and pathogen transmission is also the sex with the greater dispersal engine. For cumulative flight duration, age and the sex-by-age interaction were significant, although sex alone was not, meaning that the endurance gap between males and females emerges and shifts across the adult lifespan rather than being a constant difference. For average flight speed, both sex and age had significant main effects, but there was no significant sex-by-age interaction, indicating that the speed difference between the sexes remains comparatively stable as the insects grow older.

Taken together, these patterns demonstrate distinct age-related changes and sexual dimorphism in the flight capacity of Aedes albopictus, with the dimorphism itself varying dynamically across ages. The authors interpret this as highly consistent with mosquito physiological development and ecological functional differentiation. In biological terms, the story makes sense: newly emerged adults must complete sclerotization and reproductive maturation, flight muscles and energy reserves change over the first days of adult life, and females in particular undergo cycles of host seeking, blood digestion and egg development that reshape their energetic priorities. Males, whose ecological role centers on locating mates rather than seeking blood hosts, face different selective pressures on sustained flight, and the data suggest these pressures translate into measurably different flight trajectories.

The public health implications of the study are considerable. Aedes albopictus has spread from its native range in Southeast Asia across every inhabited continent over the past several decades, aided by the global trade in used tires and other water-holding containers that harbor its eggs and larvae. Because female mosquitoes can transmit dengue, chikungunya, Zika and yellow fever viruses, quantitative estimates of how far females of a given age can fly feed directly into models of epidemic spread, surveillance design and the placement of traps and control barriers. The authors emphasize that their findings offer a quantitative basis for predicting the dispersal potential of the species and for optimizing the timing and targets of control measures, information they describe as being of great reference value for the precise prevention and control of mosquito-borne infectious diseases such as dengue fever.

The study also illustrates a broader principle in vector biology: control programs that ignore the age structure and sex structure of vector populations may misallocate resources. If flight capacity peaks and declines at specific ages, then interventions aimed at interrupting dispersal, such as source reduction around breeding sites, spatial repellents or the release of sterile or Wolbachia-infected males, can be timed and targeted more effectively when the flight behavior of each sex and age class is known. Conversely, assuming that all adults pose an equal dispersal risk could lead to surveillance gaps precisely where and when the strongest fliers are active. By anchoring those assumptions in systematic flight mill data and rigorous statistical modeling, this research turns a basic entomological question into actionable epidemiological knowledge, and it underscores how much practical value can still be extracted from carefully executed laboratory studies of a familiar backyard pest.

Subject of Research: Age- and sex-dependent flight capacity of the mosquito Aedes albopictus measured by tethered flight

Article Title: The potential flight capacity of Aedes albopictus

Article References: Li, Y.-H., Zhang, Z.-Z., Fu, T., Liu, X.-B., Cui, J.-X., Cheng, P., & Guo, Y.-H. (2026). The potential flight capacity of Aedes albopictus. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07721-6

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07721-6

Keywords: Aedes albopictus, Asian tiger mosquito, flight capacity, flight mill, tethered flight, sexual dimorphism, mosquito age, vector biology, dengue, mosquito-borne disease, dispersal, Parasites & Vectors

The research team, based at Brigham and Women’s Hospital, followed thirty wild-type pups from three litters through four developmental milestones: postnatal day 0 (P0), day 8 (P8), day 21 (P21), and eight weeks of age. Using the VisualSonics Vevo F2 high-frequency ultrasound system with transducers operating between 25 and 71 MHz, the investigators captured images of hearts beating at rates of 400 to 600 beats per minute with exceptional spatial and temporal resolution. At birth, when a pup weighs barely more than a gram and its left ventricle measures roughly 1.5 millimeters across, imaging was performed without anesthesia or hair removal, with animals gently restrained on a heated platform. From P8 onward, a standardized isoflurane protocol maintained heart rates above 400 beats per minute while body temperature was held at 37 degrees Celsius, minimizing the hemodynamic variability that anesthesia can otherwise introduce.

The structural findings chart an astonishing trajectory of growth. Body weight rose from 1.25 grams at birth to nearly 21 grams at adulthood, while the left ventricular end-diastolic volume expanded almost tenfold, from about 6.4 microliters to 59 microliters. Ventricular walls thickened in parallel, with the systolic anterior wall more than doubling from birth to weaning and continuing to grow into adulthood. Perhaps most intriguing was the behavior of body-weight-indexed left ventricular mass, which surged during the early postnatal and juvenile periods before declining toward adult values. This transient overshoot, the authors note, mirrors the well-described postnatal transition in which cardiomyocytes shift from proliferative expansion to hypertrophic growth, with the heart briefly outpacing the body before mass and body weight rescale proportionally at maturity.

Counterintuitively, conventional indices of pumping performance declined steadily across development. Ejection fraction fell from 69 percent at birth to 60 percent at eight weeks, and fractional shortening followed a similar downward path. Rather than signaling weakening hearts, the authors explain, this decline reflects geometry and loading: as the ventricular cavity expands disproportionately relative to stroke volume, and as systemic afterload rises with maturation, volumetric efficiency measures naturally decrease even as the heart muscle itself grows stronger. Crucially, the strain measurements told a different story. Global circumferential strain, endocardial circumferential strain, and global radial strain all remained statistically stable from P8 through adulthood, indicating that the intrinsic contractile machinery of the myocardium is established early and preserved intact through the storms of growth and remodeling.

Strain analysis, enabled by speckle-tracking software that follows the natural acoustic markers within heart tissue frame by frame, quantifies how much the ventricular wall deforms during each beat. Longitudinal strain captures shortening along the base-to-apex axis, circumferential strain measures shortening around the chamber’s circumference, and radial strain records wall thickening toward the cavity. Because these indices depend on the coordinated behavior of individual contractile units rather than on chamber geometry, they are considered exquisitely sensitive detectors of early dysfunction, often flagging impairment in disease models long before ejection fraction budges. The one strain parameter that did change was myocardial global longitudinal strain, which became significantly more negative, from minus 8.8 percent at P8 to minus 11.9 percent at P21, suggesting selective maturation of the longitudinal contractile pathway during the juvenile period.

Diastolic function, the heart’s capacity to relax and fill, matured along its own timetable. From P8 onward, early and late transmitral filling velocities climbed steadily, with the E/A ratio peaking at day eight before stabilizing. Tissue Doppler velocities at the mitral annulus, including the early relaxation velocity e-prime, the late atrial contraction velocity a-prime, and the systolic annular velocity s-prime, all increased progressively into adulthood. Right ventricular function, tracked through tricuspid annular plane systolic excursion, nearly doubled from 0.40 millimeters at P8 to 0.78 millimeters at eight weeks. Left atrial areas grew in step with the rest of the heart, though fractional area change fluctuated without a consistent directional trend. These trajectories align with known postnatal refinements in calcium-handling proteins such as SERCA2a and ryanodine receptor 2, and with the metabolic switch from glycolysis to fatty-acid oxidation that newborn cardiomyocytes undergo shortly after birth.

One of the study’s most striking discoveries emerged when the data were split by sex. Most conventional parameters showed no sex-specific developmental patterns, but strain imaging revealed a clear divergence in late adolescence. By eight weeks, males exhibited significantly more negative longitudinal strain and higher radial strain than females, and systolic annular velocity showed the same pattern, with males reaching 21.5 millimeters per second versus 17.3 in females. Stroke volume also displayed a significant time-by-sex interaction. The timing is telling: the divergence between P21 and week eight coincides with pubertal maturation and the surge in circulating androgens, and it is consistent with prior work showing that isolated cardiomyocytes from adult male mice contract more vigorously than those from females, likely through testosterone-driven modulation of calcium handling and myofilament function.

Notably, this mouse pattern inverts the human picture, where women typically show greater myocardial strain values than men. The authors point to fundamental species differences as likely explanations: adult mouse ventricles predominantly express the fast-kinet ics alpha myosin heavy chain, whereas human ventricles express the slower beta isoform, and the tenfold difference in resting heart rate between the species fundamentally alters contraction-relaxation dynamics. Sex differences in cardiac function are also dynamic across the lifespan; aging studies suggest the male advantage seen at eight weeks may reverse later in life, with females maintaining better contractility into old age. For researchers translating murine findings to human cardiology, the message is unambiguous: sex- and species-specific normative values are essential, and extrapolating adult or human reference ranges to neonatal and juvenile mice risks misjudging both disease severity and therapeutic efficacy.

The study also functions as a technical manual for a notoriously difficult measurement. The authors document a systematic 12.3 percent overestimation of ejection fraction by short-axis M-mode derived from the Teichholz formula compared with B-mode Simpson’s monoplane volumetry, a bias that persisted at every developmental stage and that they recommend accounting for, particularly in disease models with regional wall motion abnormalities. They further emphasize maintaining normothermia in neonatal pups, which cannot thermoregulate and are prone to hypothermia-induced bradycardia, transferring maternal scent to gloved hands before handling to prevent rejection by dams, positioning the M-mode cursor perpendicular to the septum at the mid-papillary level while avoiding papillary muscle inclusion, and keeping Doppler angles below 45 degrees to prevent velocity underestimation. A printable echocardiography quicksheet summarizing key reference values accompanies the publication as a bench-side tool.

The limitations are candidly acknowledged: the data derive exclusively from Jackson Laboratory C57BL/6 mice, whose developmental trajectories may differ across strains; volumetric parameters rest on geometric assumptions that strain measurements avoid; and the extreme technical constraints of imaging newborn hearts meant that strain, Doppler, and right ventricular assessments could not be performed at P0. Future directions include comprehensive right ventricular and large-vessel characterization, integration with invasive pressure-volume loop analysis, and extending the serial observations into aging to trace how the early-life sex differences evolve across the lifespan. For now, the study stands as the definitive developmental atlas of the laboratory mouse heart, one that promises to sharpen the interpretation of countless cardiac disease models and, by reducing misclassification of phenotypes, to trim both animal usage and cost in preclinical research.

Subject of Research: Postnatal cardiac development and myocardial strain in C57BL/6 mice assessed by high-frequency echocardiography

Article Title: Prospective echocardiographic characterization of postnatal cardiac development in C57BL/6 mice: Strain analysis between birth and adulthood

Article References: Jo, S., Spyropoulos, G., Hart, L. G., Covington, T. A., Pandey, A. K., Michel, T., & Spyropoulos, F. (2026). Prospective echocardiographic characterization of postnatal cardiac development in C57BL/6 mice: Strain analysis between birth and adulthood. Physiological Reports, 14(18), Article e71113. https://doi.org/10.14814/phy2.71113

Image Credits: AI Generated

DOI: 10.14814/phy2.71113

Keywords: echocardiography, strain analysis, C57BL/6 mice, cardiac development, speckle-tracking, ejection fraction, diastolic function, sexual dimorphism, left ventricle, normative values, preclinical imaging, Physiological Reports

The maxillary sinuses are air-filled cavities hollowed out of the cheekbones, one on each side of the nose. Because they sit within some of the densest bone of the midface, they frequently survive fires, explosions, and other events that destroy more fragile skeletal landmarks. Forensic scientists have long suspected that these cavities differ between men and women, since male skulls tend to be larger and more robust overall. Earlier studies using cone-beam computed tomography in Egyptian, Indian, Chinese, and Yemeni populations confirmed measurable differences in sinus volume and dimensions. What remained unclear was how reliably those differences could be combined into a single, defensible classification—and whether the nasal structures nearby could add discriminating power.

To find out, researchers led by Haidy M. Fakher of Benha University and Eman S. Shaltout of Assiut University assembled a comparative cross-sectional dataset of 195 adult Egyptians: 100 females and 95 males, drawn from two geographically distinct regions. One hundred four participants came from Assiut in Upper Egypt, and 91 from Benha in Lower Egypt. Each person had undergone a computed tomography scan of the paranasal sinuses, the standard CT protocol used to image this region. Written informed consent was obtained from all participants, and the study received approval from the Assiut University Committee on Research Ethics, in compliance with the Declaration of Helsinki.

From each scan, the team extracted six dimensions of the maxillary sinuses and three nasal measurements, including the nasofrontal angle and the distance from the nasion—the bridge of the nose where it meets the forehead—to the nasal tip. They also recorded age and engineered ten additional derived features, bringing the total to 20 variables for the machine learning analysis. This feature engineering step matters: raw anatomical distances often carry redundant or correlated information, and ratios or combined indices can reveal dimorphism that individual measurements miss. The researchers then faced a classic machine learning design question: in what order should feature selection and hyperparameter tuning be performed?

They answered it by building two competing analytical frameworks. Framework 1 and Framework 2 differed in the sequence in which feature selection and hyperparameter optimization were applied. Within each framework, the team tested six classifiers—among them Random Forest, Support Vector Machine, and gradient boosting methods such as XGBoost, LightGBM, and CatBoost—crossed with five feature-selection methods. Performance was evaluated with a battery of standard metrics: accuracy, the area under the receiver operating characteristic curve (AUC), precision, recall, F1-score, and specificity. This kind of systematic sweep is increasingly common in forensic anthropology, where researchers have moved from traditional discriminant function analysis toward algorithms capable of capturing nonlinear relationships among skeletal measurements.

The results showed statistically significant sex-related differences in several of the measurements, though with notable regional variation between Upper and Lower Egypt—a reminder that craniofacial morphology is shaped by both sex and population history. Framework 2, which applied feature selection and hyperparameter optimization in a different order, generally outperformed Framework 1. The best-performing models achieved AUCs of 0.771 and 0.768, and the highest accuracy reached 74.4 percent. Those numbers describe what statisticians call moderate discriminative power: far better than a coin flip, and genuinely useful as corroborative evidence, but not yet in the 90-plus percent range achieved when the full skull or pelvis is available.

Perhaps the most practically valuable finding was which features carried the most weight. The nasofrontal angle, the nasion-to-tip distance, and the mean anteroposterior maxillary dimension emerged as the most consistent predictors across models. In plain terms, the shape of the nose where it meets the brow and the front-to-back depth of the cheek sinus did much of the classification work. That nasal measurements proved robust is significant, because the external nose itself is cartilage and rarely survives, but its bony framework—the nasal aperture, the nasion, the underlying cavity architecture—is preserved in bone and easily captured on a CT scan of the head.

The study’s regional findings add an important caveat for practitioners. Because the strength of sexual dimorphism varied between the Assiut and Benha samples, models trained on one population may not transfer cleanly to another. This echoes a well-established principle in forensic anthropology: sex estimation standards are population-specific, and applying a formula derived from one ancestry group to remains from another can introduce systematic error. The Egyptian data suggest that even within a single country, north–south geographic variation is large enough to register in sinus and nasal metrics, which argues for building locally calibrated models rather than importing thresholds from other populations.

The methodological comparison embedded in the study also carries lessons for the growing field of machine learning in forensic anthropology. Recent reviews have catalogued a rapid expansion of AI applications in this discipline, from cranial data mining to deep learning on cephalometric images, but results vary widely depending on pipeline choices. By showing that the ordering of feature selection and hyperparameter optimization measurably affects performance, the Egyptian team highlights a decision point that many published studies leave unexamined. Their use of interpretable model-agnostic importance analysis, rather than treating the classifiers as black boxes, also aligns with a broader push for transparency in algorithms that may one day inform court testimony.

Where does this leave the sinuses in the forensic toolkit? The authors conclude that CT-based nasal and maxillary sinus anthropometry shows moderate utility for sex estimation in Egyptians, with machine learning improving classification by capturing complex morphometric relationships that simpler statistical methods miss. For identification teams working with incomplete remains, the message is that these protected midface structures can serve as a meaningful secondary indicator when primary skeletal landmarks are absent—best used alongside other evidence rather than in isolation. With no external funding and data available from the corresponding author upon reasonable request, the study stands as a careful, population-anchored step toward AI-assisted identification, and a demonstration that even the hidden air spaces of the face can testify when the rest of the skeleton cannot.

Subject of Research: Machine learning-based forensic sex estimation from CT-derived nasal and maxillary sinus measurements in an Egyptian population

Article Title: Machine learning-driven forensic sex prediction using CT-based nasal and maxillary sinus metrics

Article References: Machine learning-driven forensic sex prediction using CT-based nasal and maxillary sinus metrics. (n.d.). https://doi.org/10.1007/s00414-026-03951-6

Image Credits: AI Generated

DOI: 10.1007/s00414-026-03951-6

Keywords: forensic anthropology, sex determination, machine learning, computed tomography, maxillary sinus, nasal morphometry, sexual dimorphism, Egyptian population, feature selection, Random Forest, support vector machine, International Journal of Legal Medicine

The research team, led by W. Aidan Martel, S. Bradley King, and senior author Rebecca V. Mountain, set out to answer two questions that previous work had left open. First, do the sex differences seen in isolation-induced bone loss simply reflect different timelines, with females eventually succumbing to the same damage if given enough time? Second, what role do the sex steroid hormones estrogen and testosterone play in mediating the skeletal response? To address these questions, the investigators housed 16-week-old C57BL/6J mice either in groups of four per cage or alone, one mouse per cage, for periods of 2, 4, or 8 weeks, and then subjected their bones to detailed structural, biomechanical, and molecular analysis.

The results were unambiguous for the males. Single housing significantly reduced bone parameters across every treatment length tested. On average, isolated male mice showed a 20 percent reduction in trabecular bone volume fraction, a key measure of the spongy, metabolically active bone found inside the ends of long bones and vertebrae. Cortical thickness, the measure of the dense outer shell of bone that provides most of a skeleton’s resistance to bending and fracture, fell by an average of 8 percent. Critically, these changes appeared remarkably fast: trabecular bone was measurably affected after as little as two weeks of isolation, suggesting that the male skeleton responds to the loss of social contact with surprising speed.

Structure alone does not determine whether a bone will break, so the team also tested mechanical performance. Bones are not simply mineral scaffolds; their ability to absorb energy and resist fracture depends on the interplay of material quality and architecture. When the researchers subjected the femurs to biomechanical testing, they found that isolation degraded the mechanical properties of the bone in male mice but not in females. In practical terms, the isolated males were left with femurs that were thinner, less dense, and weaker, a combination that in a living animal would translate into a substantially elevated fracture risk.

The females told a very different story. Across all three treatment durations, the overall bone phenotype of isolated female mice was essentially unaffected. Trabecular and cortical parameters held steady, and biomechanical performance remained comparable to that of group-housed controls, even after eight weeks of single housing. This finding rules out the simplest explanation for the sexual dimorphism, namely that females merely respond more slowly. Whatever protects the female skeleton from the consequences of social isolation, it is not a matter of delayed onset but of a fundamentally different biological response.

Yet the female skeleton was not entirely silent. When the researchers measured bone turnover markers, the biochemical signals of bone formation and bone resorption that circulate in the blood, they found that isolated females showed an increase after just two weeks of isolation. Bone remodeling is a continuous process in which osteoclasts break down old bone and osteoblasts lay down new bone, and shifts in turnover markers indicate that the cellular machinery had been perturbed even though the net structure remained intact. The authors interpret this as evidence that isolated females experienced changes in bone remodeling dynamics that somehow resolved without producing measurable bone loss, a decoupling that may itself hold clues to the protective mechanism.

The search for a hormonal explanation produced one of the study’s most intriguing results. In male mice isolated for four or eight weeks, the researchers observed alterations in the expression of estrogen-related genes, even though circulating estrogen levels themselves were unchanged. This dissociation between gene expression and circulating hormone concentration suggests that the skeletal response to isolation may be mediated locally, at the level of the bone tissue itself, rather than through systemic changes in sex steroid availability. It also raises the possibility that estrogen signaling, traditionally studied in the context of female physiology, plays an underappreciated role in the male skeleton’s response to psychological stress.

The clinical resonance of these findings is considerable. Social isolation and loneliness affect a large and growing share of the human population, particularly older adults, and epidemiological studies have associated them with elevated risks of numerous chronic conditions. If a sexually dimorphic relationship between social contact and bone health exists in humans, as the murine data suggest it might, then men who are socially isolated could represent an unrecognized population at elevated risk of osteoporosis and fragility fracture. Osteoporosis is already underdiagnosed in men, in part because the disease is often perceived as a condition of postmenopausal women, and a psychosocial contribution to male bone loss could sharpen both screening and prevention strategies.

The study also sounds a cautionary note for the research community. Single housing is a routine practice in biomedical research, whether for experimental necessity, behavioral phenotyping, or animal management, and the new data show that this housing condition is not physiologically neutral, at least for male rodents. Any study using individually housed male mice as a baseline could be inadvertently measuring the skeletal consequences of isolation superimposed on the experimental variable of interest. The authors note that these findings have important implications for pre-clinical rodent models utilizing single housing, and the rapid two-week onset of bone changes suggests that even short housing periods may be sufficient to confound skeletal endpoints.

Many questions remain. The precise mechanism linking social isolation to osteoclast and osteoblast activity is still unknown, as is the identity of the factor that shields female bone. The role of testosterone, which the study set out to examine, and the functional significance of the altered estrogen-related gene expression in males, will require further investigation. What is already clear, however, is that the skeleton listens to the social environment, and that it does so differently in males and females. As loneliness becomes an increasingly prominent public health concern, this work suggests that its costs may be written not only in the brain and the heart, but in the very architecture of bone, and that sex must be part of any equation that seeks to predict who pays the price.

Subject of Research: Sex-dependent effects of social isolation on bone health in adult mice

Article Title: Short- and long-term effects of social isolation on adult murine bone are sex-dependent

Article References: Martel, W. A., King, S. B., Buchanan, E., Merrill, B. M., Stohn, J. P., Brooks, D. J., Barlow, D., Motyl, K. J., & Mountain, R. V. (2026). Short- and long-term effects of social isolation on adult murine bone are sex-dependent. Biology of Sex Differences. https://doi.org/10.1186/s13293-026-00995-6

Image Credits: AI Generated

DOI: 10.1186/s13293-026-00995-6

Keywords: social isolation, bone health, sexual dimorphism, osteoporosis, trabecular bone, cortical bone, bone turnover, estrogen, testosterone, murine model, loneliness, biomechanics

The study, published in the journal iScience, used induced pluripotent stem cell, or iPSC, lines derived from three healthy male donors aged 27 to 36 and three healthy female donors aged 20 to 49. The researchers guided these stem cells through a developmental journey in a dish: first into mesoderm, then into hemogenic endothelium that produces hematopoietic stem and progenitor cells, and finally into monocytes nurtured with interleukin-3 and macrophage colony-stimulating factor. The monocytes were collected over multiple weeks and cultured further until they matured into macrophages. Crucially, the entire process took place in serum-free medium, which limits exposure to circulating hormones. Because the cells never lived inside a body, any differences that emerged between male-derived and female-derived macrophages could be attributed largely to inherent cellular genetics, namely the chromosomal complement, rather than to years of hormonal and environmental conditioning.

Before any experiments on inflammation, the team verified that their lab-grown macrophages were the real thing. Flow cytometry confirmed expression of the surface markers CD11b, CD14, HLA-DR, and SIRP-alpha, the fingerprint of cells in the myelomonocyte lineage, and immunostaining revealed the pan-macrophage marker CD68. Functional testing showed that the cells could phagocytose fluorescently tagged latex beads, a proxy for their ability to engulf dead cells and debris, and here the sexes performed identically. The same held true when the researchers compared their iPSC-derived macrophages with primary macrophages grown from monocytes isolated from male and female blood donors, supporting the validity of the stem cell model. Migration toward the chemoattractant CXCL12 in a Boyden chamber assay also showed no statistically significant difference between the sexes, although female macrophages trended toward slightly greater movement.

The transcriptome told a subtler story. Bulk RNA sequencing of the resting macrophages, analyzed by principal component analysis and hierarchical clustering, showed that the male lines clustered tightly together while the female lines spread across a much wider range, hinting at hidden variables such as unknown menopausal status among the female donors. Although the first two principal components explained only about 30 percent of the variance, the top 1,000 genes still sorted samples by biological sex rather than by donor, suggesting that sex, not individual identity, was the dominant driver of the transcriptional landscape. When the differentially expressed genes were mapped to their chromosomes, more than half landed on the X and Y chromosomes, a striking signal that sex-linked gene expression underlies much of the baseline dimorphism.

Those baseline genetic differences translated into at least one measurable functional gap. Resting female macrophages secreted significantly more monocyte chemoattractant protein-1, or MCP-1, than their male counterparts. MCP-1 is no bit player; it is a major chemotactic and activating signal that recruits monocytes and macrophages to sites of inflammation, so elevated production by female cells could shape how an inflammatory response unfolds. Female cells also produced slightly higher levels of interleukin-1 beta, IL-6, IL-10, and interferon-alpha 2, while male cells produced somewhat more IL-8, though these differences did not reach statistical significance. Enrichment analysis of the differentially expressed genes flagged pathways including ferroptosis, complement and coagulation cascades, HIF-1 signaling, the cell cycle, and regulation of the actin cytoskeleton, along with gene ontology terms tied to macrophage activation and cytokine production.

The real drama began when the researchers dosed the cells with lipopolysaccharide, or LPS, a component of the outer membrane of Gram-negative bacteria that triggers acute inflammation through toll-like receptor 4 signaling. In the sequencing data, LPS clearly separated stimulated cells from resting controls along one principal axis, and male from female cells along another. The separation between sexes was far more pronounced under inflammation than at rest, indicating that the dimorphism is not merely present but actively amplified by an inflammatory challenge. When the team searched for genes that changed in opposite directions between the sexes, or changed significantly in one sex while remaining flat in the other, the chemokine signaling pathway emerged as the most significantly perturbed, alongside metabolic pathways, cytokine-cytokine receptor interactions, Th1 and Th2 cell differentiation, apoptosis, and extracellular matrix-receptor interactions.

Within the chemokine signaling circuit, the analysis pointed to upregulation of CCL15 and CCL20 and of the signaling intermediates SOS1, SOS2, and BRAF, with downregulation of MAPK3, perturbations expected to cascade through Jak-STAT and MAPK pathways and drive changes in cytokine output, migration, and cell death. Protein-level measurements bore this out in a sex-specific pattern. Both sexes ramped up cytokine production in response to LPS, but the profiles diverged sharply: male macrophages produced significantly more IL-1 beta, TNF-alpha, IL-6, IFN-alpha 2, IL-10, and IL-23, whereas female macrophages produced significantly more IFN-gamma, IL-8, and IL-17A. Notably, these patterns echo published reports from primary human cells, in which men show stronger monocyte-derived cytokine responses to endotoxin, lending physiological credibility to the stem cell model.

Perhaps the most intriguing finding was chromosomal geography. At rest, most differentially expressed genes sat on the sex chromosomes; after LPS, that flipped. Of the 304 genes differentially expressed between male and female macrophages under inflammatory conditions, only 18.1 percent mapped to sex chromosomes, and once baseline differences were accounted for, the sex-linked fraction fell below 3 percent, with the largest share of genes on chromosome 1. The sex-linked genes that did change included X-linked players such as CSTF2, UXT, MBTPS2, HUWE1, and MECP2, upregulated in males, and NOX1, SLC6A8, and TSPYL2, downregulated in males, plus Y-linked shifts in DDX3Y and RPS4Y1. Several of these genes govern NF-kappaB signaling, epigenetic regulation, and reactive oxygen species production, processes with obvious inflammatory stakes. One candidate, the NADPH oxidase NOX1, was confirmed at the protein level: male macrophages produced modestly but significantly more NOX1 protein during inflammation, consistent with prior reports that oxidative stress runs higher in males across species.

The authors are careful about the limits of their work. Six iPSC lines cannot capture the full breadth of human population diversity, and differences between iPSC-derived macrophages and their blood-derived counterparts remain. The single LPS time point misses the dynamic arc of inflammation, and the female donors’ menopausal status, unknown here, may have inflated variability. Still, the model scales naturally through large iPSC banks holding lines from hundreds of donors, and future iterations could embed these macrophages into organ-on-a-chip systems to restore cell-cell interactions lost in isolation. The implications reach into some of medicine’s most stubborn sex disparities, from COVID-19 severity, where cytokine differences between the sexes are well documented, to autoimmune disease, obesity, asthma, cardiovascular disease, and aging. If most inflammation-driven dimorphism is written on the autosomes, steered by epigenetic echoes of the sex chromosomes, then drug developers may need to rethink a long-standing habit: dosing men and women identically on the assumption that their immune cells are interchangeable.

Subject of Research: Sex-based differences in human iPSC-derived macrophage inflammatory responses

Article Title: LPS stimulation reveals male and female dimorphism in human iPSC-derived macrophages

Article References: Graney, P. L., Tavakol, D. N., Lock, R. I., Chen, C., Samaritano, M., Sanchez, E., Hachmann, N. P., Rosales, M. P., Friedman, R., & Vunjak-Novakovic, G. (2026). LPS stimulation reveals male and female dimorphism in human iPSC-derived macrophages. iScience, 29(10), Article 117565. https://doi.org/10.1016/j.isci.2026.117565

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117565

Keywords: macrophages, iPSC, sexual dimorphism, LPS, inflammation, cytokines, sex chromosomes, NOX1, chemokine signaling, immunology, transcriptomics, TLR4

The research, led by Georgia Kontogianni and Panagiotis Kouzis as co-first authors, with Georgios Kararigas and Themis Alissafi as co-senior authors, brings together teams from the Biomedical Research Foundation Academy of Athens, the National and Kapodistrian University of Athens, the University of Tirana, the University of Tours, the University of Crete, FORTH and the University of Nicosia. The group focused on regulatory T cells, or Tregs, the specialized CD4-positive lymphocyte population that acts as the immune system’s built-in restraint. Tregs patrol the periphery and suppress excessive activation of self-reactive lymphocytes, maintaining what immunologists call peripheral tolerance. Previous work had shown that Tregs are directly affected by checkpoint inhibitors, which target inhibitory signaling pathways that Tregs themselves rely upon, and that during immune-related adverse events these cells undergo extensive inflammatory and metabolic reprogramming, acquiring traits that echo the effector cells they are supposed to restrain. What remained unknown was whether this reprogramming follows the same trajectory in men and women.

The rationale for asking this question is grounded in decades of immunological observation. Women mount stronger humoral and cellular immune responses to infection and vaccination, are far more susceptible to many autoimmune diseases, including lupus, Hashimoto’s thyroiditis and multiple sclerosis, and show sex-dependent differences in Treg biology and inflammatory signaling. Estrogen, androgen and X-linked genetic factors all feed into immune gene regulation. If biological sex shapes the baseline behavior of Tregs, it seemed plausible that it would also dictate how those cells respond when checkpoint blockade or spontaneous autoimmunity pushes the immune system toward self-attack. Testing that idea at scale required a bioinformatics approach rather than a single-cohort experiment, because the relevant patient populations are scattered across clinical studies.

The team therefore performed a sex-based integrative transcriptomic analysis of bulk RNA sequencing datasets generated from peripheral blood Tregs. The datasets came from patients with advanced melanoma and additional solid tumors treated with anti-PD-1 immunotherapy, from individuals living with chronic autoimmune diseases, and from healthy controls. By separating the data into male and female cohorts, the researchers could run differential gene expression, pathway enrichment and network-level analyses independently for each sex, mapping the inflammatory, metabolic and tolerance-associated transcriptional programs that accompany each condition. This design allowed a direct comparison not only between disease and health, but between the sexes and between two distinct contexts of tolerance breakdown: drug-induced toxicity and spontaneous autoimmunity.

The results reveal a layered picture. During spontaneous autoimmune disease, female-derived Tregs exhibited markedly broader transcriptional remodeling than their male counterparts. The female cells showed extensive enrichment of biological processes spanning immune regulation, inflammatory signaling, metabolism and oxidative stress, suggesting that in women, loss of tolerance engages a wide swath of the Treg transcriptional machinery simultaneously. Male-derived Tregs, by contrast, displayed comparatively restricted remodeling, involving a narrower set of immune-related and metabolic pathways. In other words, the depth and breadth of the regulatory cell’s response to autoimmunity is not the same in both sexes, a finding that helps explain why autoimmune susceptibility and severity so often diverge between men and women.

Immune-related adverse events, however, told a different story. Checkpoint inhibitor-associated toxicity produced a distinct pattern of sex-dependent transcriptional organization in Tregs, one that did not simply mirror what the researchers observed in autoimmunity. Although the two conditions share many underlying biological processes, since both represent failures of peripheral tolerance, the degree, directionality and network-level organization of the transcriptional responses differed substantially between the sexes and between disease settings. The same cells, facing the same fundamental problem of lost tolerance, appear to solve or succumb to it along different molecular routes depending on both the sex of the patient and the inflammatory context in which tolerance was disrupted. This argues against a single, uniform program of Treg failure and in favor of disease-specific, sex-shaped trajectories of reprogramming.

The technical implication is significant for how immunologists interpret single-cell and bulk transcriptomic studies. If male and female Tregs organize their responses differently at the pathway and network level, then pooling the sexes, as many studies historically have done, may obscure biologically meaningful signals or generate misleading averages. The authors emphasize that biological sex does not impose one common regulatory program on Tregs; rather, it shapes disease-specific transcriptional trajectories according to the inflammatory environment. That distinction matters for biomarker development, because a transcriptional signature predictive of severe colitis in a male patient treated with anti-PD-1 therapy may not hold for a female patient, and vice versa. Incorporating sex as a biological variable from the earliest stages of study design, rather than as an afterthought in the analysis, emerges as a practical necessity for personalized immunology.

The clinical stakes are considerable. Immune-related adverse events remain a leading cause of treatment interruption and morbidity in oncology, and clinicians currently lack reliable tools to predict which patients will develop severe toxicities. If Treg reprogramming trajectories diverge by sex, sex-stratified biomarkers could improve risk stratification before and during checkpoint inhibitor therapy, potentially guiding earlier intervention with immunosuppression or closer monitoring. Beyond oncology, the findings offer a molecular framework for a long-standing epidemiological puzzle: why women dominate the incidence of many autoimmune diseases while men, once affected, sometimes follow different disease courses. The observation that female Tregs undergo broader remodeling during autoimmunity provides a transcriptional correlate of that epidemiology, and a starting point for mechanistic work into the hormonal and genetic drivers behind it.

For now, the study stands as a reminder that the immune system is not a one-size-fits-all machine. The researchers, supported in part by a European Research Council grant under Horizon 2020 and by the Hellenic Foundation for Research and Innovation, and conducted within the framework of the COST Action ENOTTA, have shown that the cells tasked with keeping immunity in check remodel themselves along paths dictated by both biology and context. As checkpoint inhibitors continue to expand across tumor types and treatment lines, understanding how sex shapes the fragile balance between tumor rejection and tissue destruction may prove essential to making these powerful therapies safer for everyone.

Subject of Research: Sex-dependent transcriptional reprogramming of regulatory T cells in immune-related adverse events and autoimmunity

Article Title: Biological sex defines regulatory T-cell reprogramming trajectories in immune-related adverse events and autoimmunity

Article References: Kontogianni, G., Kouzis, P., Gogas, H., Rumano, M., Mulleman, D., Verginis, P., Kararigas, G., & Alissafi, T. (2026). Biological sex defines regulatory T-cell reprogramming trajectories in immune-related adverse events and autoimmunity. Biology of Sex Differences. https://doi.org/10.1186/s13293-026-00980-z

Image Credits: AI Generated

DOI: 10.1186/s13293-026-00980-z

Keywords: regulatory T cells, immune checkpoint inhibitors, immune-related adverse events, autoimmunity, biological sex, peripheral tolerance, transcriptomics, anti-PD-1 therapy, sexual dimorphism, personalized immunology, Biological, defines

The study, published in Sports Medicine – Open, was led by Simone Montenegro of the German Sport University Cologne, together with Pamela Wicker, Tim Wiedenmann, Ludwig Rappelt and Lars Donath. The team drew on the Open Powerlifting database, restricting their sample to drug-tested, unequipped “classic” powerlifting competitions sanctioned by the International Powerlifting Federation and its national affiliates between January 2015 and March 2026. To ensure a homogeneous contemporary population, they limited analysis to full-power results comprising the squat, bench press and deadlift, and to athletes aged 21 to 49 years, a window designed to encompass the age of peak competitive performance in the sport, reported at roughly 27 years.

A crucial methodological decision shaped everything that followed. Large athletic databases are noisy: a single athlete may appear dozens of times, and most of those entries capture sub-maximal performances rather than career-best efforts. To solve this, the researchers applied what they call a “Best-Ever” filter. Each unique athlete was linked by name and sex, and only the single competition containing their highest recorded total was retained. Anchoring on the best-total competition, rather than stitching together best lifts from separate events, preserved the internal coherence of the three lifts as one simultaneously achieved performance. The final sample comprised 101,898 athletes, of whom 67,789 were male and 34,109 were female.

The statistical engine of the study was quantile regression, a technique that estimates specific points of the performance distribution, in this case the 50th, 75th, 90th and 99th percentiles, independently, rather than focusing only on the average lifter. Standard errors and confidence intervals were derived through bootstrap resampling to ensure robust inference at the extreme quantiles, and the researchers labeled the four tiers Intermediate, Advanced, Elite and World Class, following terminology common in strength and conditioning practice. The analytical unit was the bodyweight multiplier, the ratio of load lifted to body mass, but the authors were explicit that the ratio served as a diagnostic tool, not a benchmark: the entire point was to test whether a single fixed multiplier could mean the same thing across the body-mass spectrum.

It cannot. The analysis revealed a highly significant, systematic, non-linear decline in relative strength with increasing body mass across all lifts, all percentiles and both sexes. The most striking illustration comes from the male world-class tier: the smoothed 99th-percentile deadlift multiplier fell from 4.37 times bodyweight in the 59-kilogram class to just 2.65 times bodyweight in the 120-plus-kilogram category. In other words, a numerical standard that an elite lightweight could achieve comfortably sits at the absolute frontier of what an elite super-heavyweight can manage. The decay coefficients are small but relentless, and the researchers quantify their meaning precisely: a coefficient of -0.01 means that for every 10 kilograms of additional body mass, an athlete’s expected multiplier drops by exactly 0.1 times, for instance sliding from a 2.1-times to a 2.0-times squat.

Perhaps the most novel finding is that this decline is not uniform across skill levels. Pairwise comparisons of the quantile slopes, conducted with Wald tests for equality of coefficients, confirmed that the rate of relative-strength decay becomes significantly steeper as performance level rises. World-class athletes at the 99th percentile lose relative strength with each kilogram of body mass considerably faster than intermediate lifters at the 50th percentile. The authors suggest a likely explanation rooted in training physiology: muscle hypertrophy follows a linear-log trajectory, so advanced lifters experience diminishing returns in muscle accretion. When elite athletes gain weight, a larger proportion of that new mass may be non-contractile tissue, bone, connective tissue and fat, that inflates the denominator of the strength-to-mass ratio without contributing to the force-producing numerator.

This mechanism connects back to one of biology’s oldest mathematical constraints, the Square-Cube Law. As a body scales up, its mass increases with the cube of its linear dimensions, while the cross-sectional area of muscle, the tissue that actually generates force, increases only with the square. Heavier athletes are therefore structurally constrained to lower strength-to-mass ratios than lighter athletes of equivalent training status, a principle long established in the biomechanics literature. The observed declines in this dataset often exceed the theoretical predictions of pure geometric scaling, and the authors point to the fat-free mass index ceiling as a contributing factor: as lifters approach their natural hypertrophic potential, further mass gain becomes progressively less functional.

The study also documented a systematic shift in what the authors call the internal lift ratio, the percentage contribution of each lift to the competitive total. In the lightest weight classes, the deadlift dominates, contributing roughly 42 to 45 percent of the total. As body mass increases, that dominance erodes: in the heaviest male categories, the gap between deadlift and squat contribution narrows from an eight-percentage-point difference to roughly two points, at approximately 39 versus 37 percent. Regression models indicated that each 10-kilogram increase in body mass is associated with about a 0.44 percentage-point reduction in the deadlift’s share and a 0.28 percentage-point increase in the squat’s share. The likely culprit is soft tissue interference: greater abdominal and thigh girth can compromise the deadlift starting position or lockout, while added body volume may assist the squat through passive joint stability and a reduced effective range of motion.

Sex differences added another layer of complexity. Female athletes exhibited a steeper mass-dependent decline in bench press and squat performance than males. At the 99th percentile, the female squat decay coefficient was -0.0136 against the male -0.0125, meaning that for every 10 kilograms of body mass, a world-class female lifter loses 0.136 times bodyweight in relative squat strength compared with 0.125 for her male counterpart. The female bench press proportion of the total remained essentially static across the mass spectrum. The authors note this upper-body discrepancy may reflect both biological differences in regional muscle distribution and sociological factors, such as lower prior exposure to upper-body training among women, citing meta-analytic evidence that females make larger relative upper-body strength gains in response to training. The practical implication is blunt: applying male-derived multipliers to female athletes sets targets that simply do not correspond to the observed female performance distribution.

To make the findings usable on the gym floor, the researchers converted their statistical models into absolute-load normative atlases, stratified by sex, lift and current IPF weight class, expressed in raw kilograms with no calculation required. A coach can now determine whether an 83-kilogram athlete’s 180-kilogram squat sits at the 50th or the 90th percentile of drug-tested competitors worldwide, and whether the deadlift and bench press sit at comparable percentiles, something no aggregate score like the Wilks or IPF Good Lift coefficient can reveal, since those formulas compress the three lifts into a single number optimized for cross-weight-class ranking. The atlases also offer an empirical anchor for weight-class transitions: because relative multipliers fall even when absolute strength is maintained, an elite athlete moving up a class faces a disproportionately steeper relative decline than an intermediate lifter making the same move. The authors caution that the atlases are current reference values rather than permanent benchmarks, noting that squat and deadlift medians can rise by roughly 2.5 to 7.5 kilograms within five-year periods, and recommend periodic re-derivation. They also acknowledge limitations, including weigh-in manipulation through weight cutting, the absence of anthropometric data such as limb lengths, and the possibility that name-based athlete matching allowed a small number of duplicate records. Still, the message to the strength community is clear: the era of one-size-fits-all bodyweight multipliers is over, and the data have finally caught up with the barbell.

Subject of Research: Percentile-based normative standards for assessing relative and absolute strength across body mass categories in competitive classic powerlifting

Article Title: Percentile-Based Normative Standards for Strength Assessment Beyond Linear Bodyweight Multipliers in Competitive Powerlifters

Article References: Montenegro, S., Wicker, P., Wiedenmann, T., Rappelt, L., & Donath, L. (2026). Percentile-Based Normative Standards for Strength Assessment Beyond Linear Bodyweight Multipliers in Competitive Powerlifters. Sports Medicine – Open, 12(1), Article 136. https://doi.org/10.1186/s40798-026-01111-z

Image Credits: AI Generated

DOI: 10.1186/s40798-026-01111-z

Keywords: powerlifting, bodyweight multipliers, normative standards, quantile regression, relative strength, squat, bench press, deadlift, weight classes, sexual dimorphism, strength and conditioning, IPF

The study, led by Yadigar Kastamoni and Kenan Öztürk of the Department of Anatomy at Süleyman Demirel University, together with Ahmet Dursun, Onur Can Şanlı and radiologist Veysel Atilla Ayyıldız, set out to reveal sex-related characteristics through morphometric measurements taken on the mandible, and to predict sex in individuals from different age groups using those variables. The work addresses one of the enduring challenges of forensic anthropology: identifying reliable, population-appropriate skeletal markers of sexual dimorphism that remain robust across the adult lifespan.

The research team analysed head and neck computed tomography images from 152 individuals, 77 males and 75 females, aged between 20 and 98 years. From these scans, the researchers generated three-dimensional reconstructions of each mandible using the RadiAnt DICOM viewer, a software platform that converts the two-dimensional slice data produced by CT scanners into volumetric models that can be measured in three dimensions. This approach reflects a broader shift in forensic science away from measurements taken with calipers on dry skulls and toward virtual anthropology, in which clinical imaging archives become rich sources of skeletal data.

The specific landmarks chosen for measurement were carefully selected regions of the mandible with well-established anatomical identities. The team measured dimensions relating to the foramen mentale, the mental foramen through which the mental nerve and vessels emerge on the front of the jaw; the condylus mandibulae, the rounded condyles that articulate with the skull at the temporomandibular joints; the incisura mandibulae, the notch between the condyle and the coronoid process on the upper margin of the ramus; and the angulus mandibulae, the angle of the jaw at the back and lower corner of the bone. In addition, the researchers measured the bigonial distance, the straight-line breadth of the jaw between the two gonion points at the angles on either side. All measurements, except those involving the mandibular angle, were carried out in RadiAnt DICOM Viewer 2020.1.1, and the resulting data were analysed statistically using SPSS 20.0 for Windows.

The results were strikingly consistent with the known biology of the human mandible. When the parameters were compared between the sexes, the mean values of all measurements, with the single exception of the left mandibular angle, were larger in males than in females. This pattern mirrors the influence of testosterone-driven bone growth during puberty, which produces a generally larger, squarer and more robust jaw in men, while hormonal and muscular factors in women tend to produce a jaw with a more obtuse gonial angle and finer proportions. The only measurement that failed to show a statistically significant sex difference was the gonial angle itself on the left side, a finding that reinforces a long-standing caution in the literature: angular measures of the jaw are notoriously variable and are influenced by age-related remodelling, tooth loss and chewing forces.

The degree of sexual dimorphism varied considerably across the measured parameters. The highest dimorphism rate was observed in the incisura mandibulae, the mandibular notch, which differed between the sexes by 14.39 percent on the right side and 14.29 percent on the left. At the opposite extreme, the angulus mandibulae showed almost no dimorphism, with differences of just 0.12 percent on the right and 0.57 percent on the left. This gradient is informative for forensic practice: it suggests that linear distances spanning the ramus, particularly between the mandibular condyle and the gonion, carry far more sex-diagnostic information than the angle of the jaw, which should be treated with caution when sexing fragmentary remains.

Indeed, the statistically significant differences between the sexes were found specifically in the distances from the condylus mandibulae to the gonion on both sides of the jaw, alongside the bigonial distance. These findings give forensic anthropologists a small set of hardy landmarks, robust bony points that survive decomposition and trauma relatively well, from which reliable linear measurements can be taken. Because the condyle and gonion are prominent structures on the ramus, they remain measurable even when the delicate alveolar portion of the jaw bearing the teeth has been damaged or lost, a common scenario in archaeological and forensic contexts.

What elevates the study beyond a simple descriptive anatomy exercise is its predictive modelling. The researchers built a logistic regression model from their measured variables, which correctly classified 91.4 percent of individuals in the development sample. A parallel discriminant function analysis achieved 90.1 percent classification accuracy on the original sample, and, crucially, retained 85.5 percent accuracy under leave-one-out cross-validation, a stringent test in which each individual is classified by a model trained on everyone else. The modest drop between original and cross-validated performance indicates that the model generalises reasonably well rather than simply memorising the training data, an important consideration for any method intended for real casework.

The authors conclude that sex estimation can be successfully performed using external measurements of the mandible, and they highlight the bigonial distance and the gonion-to-condyle measurements as particularly valuable parameters for sex differentiation. They suggest the method may prove useful in anatomy, forensic medicine and anthropology, especially in studies requiring sex estimation. This positions the mandible alongside the pelvis and skull as a first-rank bone for sex estimation, with particular value in contexts where those more classically dimorphic elements are missing. The mandible is also among the densest and most durable bones in the human skeleton, frequently surviving fire, fragmentation and long burial, which makes any validated method for reading sex from it disproportionately useful.

The study also carries broader implications for how forensic science will develop in the coming years. Computed tomography is now routinely performed in hospitals worldwide, and archives of clinical scans represent vast, untapped populations of reference data. Virtual osteometry of this kind does not require a physical skeleton at all: it can be applied ante-mortem to living patients in identification contexts, and post-mortem using clinical or forensic CT, avoiding destructive sampling of evidence. Earlier work cited by the team, including validation studies of three-dimensional CT measurements and postmortem CT morphometry of the mandible in Japanese populations, had already established the technical reliability of imaging-based measurement; the new study extends that framework with a large, wide-ranging adult sample spanning nearly eight decades of age, from 20 to 98 years.

As with all skeletal sex-estimation methods, population specificity remains the central caveat. The dimensions of the mandible vary across ancestral and geographic groups, and the classification functions derived here were developed on a Turkish sample; forensic practitioners applying them elsewhere would need to validate or recalibrate the model against local reference data before relying on it in identification casework. The retrospective design, approved by the Human Research Ethics Committee of Süleyman Demirel University with informed consent waived for anonymised data, also means the findings describe a clinical imaging population rather than a random demographic one. Nevertheless, with cross-validated accuracy approaching ninety percent from a handful of simple linear measurements, the message of the study is clear and, for a field where even a single additional clue can resolve an identification, quietly revolutionary: the jawbone remembers who you were, and it is willing to tell.

Subject of Research: Sex estimation from morphometric measurements of the human mandible in three-dimensional computed tomography images

Article Title: Sex estimation from the mandible in 3D computed tomography images

Article References: Kastamoni, Y., Dursun, A., Şanlı, O. C., Ayyıldız, V. A., & Öztürk, K. (2026). Sex estimation from the mandible in 3D computed tomography images. International Journal of Legal Medicine. https://doi.org/10.1007/s00414-026-04001-x

Image Credits: AI Generated

DOI: 10.1007/s00414-026-04001-x

Keywords: sexual dimorphism, mandible, computed tomography, forensic anthropology, 3D imaging, morphometry, sex estimation, bigonial distance, logistic regression, discriminant analysis, human identification, osteometric analysis

The research team, led by Khajid Ullah Khan and Muhammad Tariq Zahid of Government College University, Lahore, together with colleagues in Pakistan and South Korea, collected 126 scorpions, 85 females and 41 males, from rocky field sites during June and July, the peak of the animals’ annual activity window. Specimens were located by day by overturning stones and by night using ultraviolet light, which causes scorpion cuticles to fluoresce. Morphological examination under a stereomicroscope documented the diagnostic features of the species, including its dark brown coloration, densely granulated carapace keels, a triangular sternum characteristic of the family Buthidae, and a bulbous reddish telson bearing a curved, dark-tipped aculeus. Females were consistently larger and thicker-bodied than males, with mean total lengths of roughly 72.8 millimeters compared with 62.9 millimeters in males, and males carried significantly more pectinal teeth, averaging about 30 to 32 per comb versus 26 in females.

To confirm species identity beyond morphology, the researchers amplified and Sanger-sequenced approximately 650 base pairs of the mitochondrial cytochrome c oxidase subunit I gene, the standard animal DNA barcode. BLAST comparison against the NCBI GenBank database returned nucleotide identities of 96.95 and 96.81 percent with existing H. tamulus sequences, and maximum-likelihood phylogenetic analysis in MEGA11 clustered the new sequences firmly within the species. The roughly three percent divergence from the nearest reference strain, which originated from a commercial insect market in China with undocumented provenance, suggests notable geographic structuring within the species, a pattern consistent with the deep intraspecific lineages documented in other scorpion genera such as Scorpio in the Levant and Alpiscorpius in the European Alps.

The centerpiece of the study was its metataxonomic analysis of the gut contents of six adult scorpions, three males and three females, dissected aseptically after surface sterilization. Genomic DNA was extracted with a bead-beating kit and sequenced on an Oxford Nanopore MinION flow cell using primers targeting the full V1 through V9 hypervariable regions of the 16S rRNA gene. The run produced 355,264 high-quality reads, averaging about 71,000 per sample with a mean length of approximately 1,390 nucleotides, effectively covering the entire gene. Because nanopore sequencing carries higher raw error rates than short-read platforms, the team clustered sequences de novo into operational taxonomic units at a deliberately relaxed 85 percent identity threshold using VSEARCH, then classified them against the SILVA reference database within the QIIME 2 pipeline, removing putative contaminants flagged in negative controls.

The results reveal a gut community dominated overwhelmingly by two bacterial phyla. Firmicutes accounted for between 79.5 and 90.4 percent of sequences across individuals, followed by Proteobacteria at 9.5 to 20.5 percent, while Actinobacteriota and Bacteroidota were barely detectable. At the class level, Bacilli made up roughly 73 percent of the community, with Gammaproteobacteria and Mollicutes contributing about 13 and 7 percent respectively. Four genera stood out as the core microbiota: Bacillus, Mycoplasma, Pantoea, and Enterobacter together comprised approximately 84 percent of all recovered 16S sequences. Bacillus alone represented 17 to 30 percent of the gut community, echoing recent findings in the black scorpion Heterometrus longimanus, where the same genus also dominates. The authors suggest Bacillus may function as a key endosymbiont, supporting antioxidant defenses, gut barrier integrity, and the synthesis of vitamins and amino acids for the host.

Perhaps the most evolutionarily intriguing member of the community is Mycoplasma, a genus of wall-less bacteria that has repeatedly surfaced in scorpion microbiome surveys. Previous work by Bolaños and colleagues documented Mycoplasma lineages in 15 scorpion morphospecies across Mexico, with cophylogenetic analysis suggesting cospeciation between the bacteria and their hosts. The new Pakistani data reinforce the idea that Mycoplasma is an indigenous, long-term associate of scorpions rather than a transient dietary contaminant, a conclusion paralleled by reports of Mycoplasma comprising up to 40 percent of the respiratory microbiota in some snake families. In the present study, Mycoplasma was roughly twice as abundant in females, averaging 10.5 percent relative abundance, as in males at 5.3 percent.

Sex emerged as a consistent theme throughout the diversity analyses. Alpha diversity metrics, including observed species, Chao1, Shannon, and Simpson indices, showed that female scorpions harbored markedly richer and more evenly distributed bacterial communities, whereas male guts were dominated by a smaller set of taxa. Two intestinal fermenters, Enterococcus and Romboutsia, were significantly enriched in females. Both genera are associated with carbohydrate and bile acid metabolism in nutrient-rich gut environments, and the authors speculate that the reproductive energy demands of females may create a more favorable niche for these bacteria, potentially influencing host energy harvest from food. Comparable sex-dependent microbiome patterns have been reported in ticks, where males and females of species such as Amblyomma americanum carry distinct communities, and in the wolf spider Pardosa astrigera, where seasonal and physiological state modulate sex-specific diversity.

To move beyond taxonomy, the researchers applied PICRUSt2, a bioinformatic tool that infers metagenome functions from 16S profiles by matching marker genes against reference genomes. The analysis predicted 23 enriched MetaCyc metabolic pathways spanning energy metabolism, amino acid and lipid biosynthesis, nucleotide metabolism, and the biodegradation of xenobiotic compounds. Male samples appeared enriched for energy metabolism and biosynthetic routes, while female samples showed greater representation of lipid metabolism and fatty acid biosynthesis pathways, hints that the sex-specific microbial differences may extend into function. The authors are careful to stress, however, that PICRUSt2 output is indicative rather than definitive: it does not measure actual gene expression, and the predictions require validation through shotgun metagenomics or transcriptomics, particularly given the study’s small sample of six individuals.

Situated in a broader ecological context, the findings portray scorpions as hosting a moderately diverse microbiome that sits above the extremely depauperate communities of social spiders, which average a Shannon index of just 0.66, yet below the hundreds to thousands of operational taxonomic units recoverable from soil or lepidopteran eggs. The overlap between the H. tamulus core genera and those documented in wolf spiders, crab spiders, and moths suggests a partially conserved gut microbial blueprint across predatory arthropods. The authors also raise an untested but plausible transmission hypothesis: because scorpions exhibit extensive brood care, including mothers provisioning enzymatically treated prey to offspring, maternal transfer could explain how these symbionts persist across generations, a mechanism previously documented in brown widow spiders.

As a first baseline for a medically iconic species in a previously unsampled region of Pakistan, the study opens concrete research avenues. Bacillus and Mycoplasma emerge as prime candidates for integrated follow-up work combining metagenomics, transcriptomics, and analysis of the venom apparatus microbiome, where Proteobacteria have been shown in other species to exceed half of the bacterial load and may contribute to nutrient cycling within the telson. Whether the gut community actively underpins H. tamulus adaptation to arid, resource-limited habitats, as microbiome-mediated stress tolerance studies in spiders and flies suggest it might in other arthropods, remains a compelling but unproven hypothesis. The authors are explicit that their six-individual sample cannot define a species-wide core microbiome; larger geographic surveys and controlled experiments will be needed before the hidden microbial partners of the world’s deadliest scorpion can be fully credited with any of its remarkable ecological success.

Subject of Research: Gut bacterial microbiome diversity and functional potential of the Indian red scorpion Hottentotta tamulus in Pakistan

Article Title: Gut Microbiome Diversity, Functional Potential, and Ecological Relevance of Hottentotta tamulus

Article References: Khan, K. U., Zahid, M. T., Mustafa, G., Tanpure, R. S., Tahir, H. M., Kumar, R., Kim, D.-W., Park, H.-K., & Jeon, B.-H. (2026). Gut Microbiome Diversity, Functional Potential, and Ecological Relevance of Hottentotta tamulus. MicrobiologyOpen, 15(5), Article e70373. https://doi.org/10.1002/mbo3.70373

Image Credits: AI Generated

DOI: 10.1002/mbo3.70373

Keywords: Hottentotta tamulus, Indian red scorpion, gut microbiome, 16S rRNA sequencing, Oxford Nanopore, Firmicutes, Bacillus, Mycoplasma, PICRUSt2, sexual dimorphism, scorpion venom, Pakistan