The metabolic cofactor Coenzyme A enhances alternative macrophage activation via MyD88-linked signaling.

Metabolites and metabolic co-factors can shape the innate immune response, though the pathways by which these molecules adjust inflammation remain incompletely understood. Here we show that the metabolic cofactor Coenzyme A (CoA) enhances IL-4 driven alternative macrophage activation [m(IL-4)] in vitro and in vivo. Unexpectedly, we found that perturbations in intracellular CoA metabolism did not influence m(IL-4) differentiation. Rather, we discovered that exogenous CoA provides a weak TLR4 signal which primes macrophages for increased receptivity to IL-4 signals and resolution of inflammation via MyD88. Mechanistic studies revealed MyD88-linked signals prime for IL-4 responsiveness, in part, by reshaping chromatin accessibility to enhance transcription of IL-4-linked genes. The results identify CoA as a host metabolic co-factor that influences macrophage function through an extrinsic TLR4-dependent mechanism, and suggests that damage-associated molecular patterns (DAMPs) can prime macrophages for alternative activation and resolution of inflammation.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Cutaneous mucormycosis with suspected dissemination in a patient with metastatic adrenocortical carcinoma.

Mucormycosis is a frequently lethal fungal infection that most commonly affects patients with poorly controlled diabetes or other immunosuppressed states. We report the case of a suspected disseminated Rhizopus infection in a patient who was pursuing naturopathic treatment including mud baths for metastatic adrenocortical carcinoma. He was empirically treated with liposomal amphotericin B but opted to stop treatment following multiorgan failure. The patient passed away on the tenth day of his hospital admission.

The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin. Their availability can be modulated within the islet by pericyte-mediated regulation of microvascular blood flow. Within the islet, both endocrine progenitor cells and the ability of endocrine cells to trans-differentiate between phenotypes can alter endocrine cell mass to adapt to changed metabolic circumstances, regulated by the within-islet trophic environment. Optimal islet function is precariously balanced due to the high metabolic rate required by beta-cells to synthesize and secrete insulin, and they are susceptible to oxidative and endoplasmic reticular stress in the face of high metabolic demand. Resulting changes in paracrine dynamics within the islets can contribute to the emergence of Types 1, 2 and gestational diabetes.

Insights into dynamic properties of water in lipidic cubic phases by 2D nuclear Overhauser effect (NOE) NMR spectroscopy.

Two-dimensional NOE (nuclear Overhauser effect) NMR spectroscopy was employed to investigate the dynamic properties of water within lyotropic bicontinuous lipidic cubic phases (LCPs) formed by monoolein (MO). Experiments observed categorically different effective residence times of water molecules: (i) in proximity to the glycerol moiety of MO, and (ii) adjacent to the hydrophobic chain towards the hydrocarbon tail of MO, as evidenced by the opposite signs of intermolecular NOE cross peaks between protons of water and those of MO in 2D 1H-1H NOESY spectra. Spectroscopic data delineating the different effective residence times of water molecules within both the gyroid (QIIG) and diamond (QIID) phase groups corresponding to hydration levels of 35 and 40 wt%, respectively, are presented. Additionally, an increase in effective residence time of water molecules in proximity to the glycerol moiety of MO in LCPs was observed upon storage at ambient temperature and in the presence of an additive lipid, cholesterol. Atom-specific NOE build-up curves for protons of water and those of MO are also given. The results presented herein provide new insight into the physicochemical properties and behaviour of water in LCPs, and demonstrate an additional avenue for experimental study of water-lipid interactions and hydration dynamics in model membranes and nanomaterials using 2D NOE NMR spectroscopy.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

The economic burden of burned patients for hospitalization in Canada.

BACKGROUND: Burn injuries pose a significant burden on both patients and healthcare systems. Yet, costs arising from the consumption of resources by these patients are rarely examined in Canada. OBJECTIVE: The objective of this study was to assess real-world costs resulting from the initial hospitalization of patients admitted to a major burn unit in Quebec, Canada. METHODS: A cost study based on a retrospective cohort was undertaken using in-hospital economic data matched to hospital chart data. Our cohort included all burn-injured patients admitted between April 1, 2017, and March 31, 2021, to the hospital's major burn unit during their initial hospitalization. Descriptive statistics were tabulated for sociodemographic and economic data. Costing data were analyzed unstratified and stratified according to burn severity (i.e., ≥ 20% of total body surface area [TBSA] vs. < 20%). Costs were presented in CAD 2021. RESULTS: Our cohort included 362 patients, including 65 (18%) with TBSA ≥ 20%. The average initial hospitalization cost was $32,360 ($22,783 for < 20% TBSA and $76,121 for ≥ 20% TBSA). CONCLUSION: Findings reveal that the total cost of the initial hospitalization, from a public hospital perspective, was $11,714,348. Our study underlines the substantial burden associated with burns and highlights the need for long-term cost evaluations.

Angle-resolved optical spectroscopy of photonic cellulose nanocrystal films reveals the influence of additives on the mechanism of kinetic arrest.

Cellulose nanocrystals (CNCs) are rod-like nanoparticles whose chiral self-assembly into photonic films has been promoted as a sustainable source of colouration. Upon drying, an aqueous CNC suspension passes through two regimes: first, a liquid phase, where the CNCs self-organise into a cholesteric liquid crystal, followed by a kinetically-arrested phase, where the helicoidal structure compresses upon loss of solvent, resulting in a solid film with vibrant structural colour. The transition between these two regimes plays an important role in the visual appearance of photonic CNC films, but details on when and how kinetic arrest occurs have remained elusive. In this work, we combine angle-resolved optical spectroscopy of photonic films (approx. 100 vol% CNC) with a model for compressed helicoidal structures to retrieve the suspension conditions during kinetic arrest (approx. 10 vol% CNC). This analysis indicates a shift in the mechanism of kinetic arrest from a glass transition at lower ionic strength to gelation at higher ionic strength, explaining the trends in domain size and film colour. In contrast, neutral additives (glucose, poly(ethylene glycol)) appear to primarily reduce the compression upon drying without affecting cholesteric behaviour, as supported by a general analytical model. These findings deepen our understanding of CNC co-assembly with various commonly-used additives, enabling better control over the production of multifunctional structurally coloured materials.

Valuing the SF-6Dv2 in the capital of Iran using a discrete choice experiment with duration.

BACKGROUND: The second version of the Short-Form 6-Dimension (SF-6Dv2) classification system has recently been developed. The objective of this study was to develop a value set for SF-6Dv2 based on the societal preferences of a general population in the capital of Iran. METHODS: A representative sample of the capital of Iran (n = 3061) was recruited using a stratified multistage quota sampling technique. Face-to-face interviews were conducted using binary choice sets from the international valuation protocol of the discrete choice experiment with duration. The conditional logit was used to estimate the final value set, and a latent class model was employed to assess heterogeneity of preferences. RESULTS: Coefficients generated from the models were logically consistent and significant. The best model was the one that included an additional interaction term for cases where one or more dimensions reached their most severe levels. It provides a value set with logical consistent coefficients and the lowest percentage of worse than death health states. Predicted values for the SF-6Dv2 were within the range of - 0.796-1. Pain dimension had the largest impact on utility decrement, whereas vitality had the least impact. The presence of preference heterogeneity was evident, and the Bayesian Information Criterion indicated the optimal fit for a latent class model with two classes. CONCLUSION: This study provided the SF-6Dv2 value set for application in the context of Iran. This value set will facilitate the use of the SF-6Dv2 instrument in health economic evaluations and clinical settings.

Functional Classification of Fusion Proteins in Sarcoma.

Sarcomas comprise a heterogeneous group of malignant tumors of mesenchymal origin. More than 80 entities are associated with different mesenchymal lineages. Sarcomas with fibroblastic, muscle, bone, vascular, adipocytic, and other characteristics are distinguished. Nearly half of all entities contain specific chromosomal translocations that give rise to fusion proteins. These are mostly pathognomonic, and their detection by various molecular techniques supports histopathologic classification. Moreover, the fusion proteins act as oncogenic drivers, and their blockade represents a promising therapeutic approach. This review summarizes the current knowledge on fusion proteins in sarcoma. We categorize the different fusion proteins into functional classes, including kinases, epigenetic regulators, and transcription factors, and describe their mechanisms of action. Interestingly, while fusion proteins acting as transcription factors are found in all mesenchymal lineages, the others have a more restricted pattern. Most kinase-driven sarcomas belong to the fibroblastic/myofibroblastic lineage. Fusion proteins with an epigenetic function are mainly associated with sarcomas of unclear differentiation, suggesting that epigenetic dysregulation leads to a major change in cell identity. Comparison of mechanisms of action reveals recurrent functional modes, including antagonism of Polycomb activity by fusion proteins with epigenetic activity and recruitment of histone acetyltransferases by fusion transcription factors of the myogenic lineage. Finally, based on their biology, we describe potential approaches to block the activity of fusion proteins for therapeutic intervention. Overall, our work highlights differences as well as similarities in the biology of fusion proteins from different sarcomas and provides the basis for a functional classification.

Differential associations between abnormal cardiac left ventricular geometry types and cerebral white matter disease.

OBJECTIVES: Reduced cardiac outflow due to left ventricular hypertrophy has been suggested as a potential risk factor for development of cerebral white matter disease. Our study aimed to examine the correlation between left ventricular geometry and white matter disease volume to establish a clearer understanding of their relationship, as it is currently not well-established. METHODS: Consecutive patients from 2016 to 2021 who were ≥18 years and underwent echocardiography, cardiac MRI, and brain MRI within one year were included. Four categories of left ventricular geometry were defined based on left ventricular mass index and relative wall thickness on echocardiography. White matter disease volume was quantified using an automated algorithm applied to axial T2 FLAIR images and compared across left ventricular geometry categories. RESULTS: We identified 112 patients of which 34.8 % had normal left ventricular geometry, 20.5 % had eccentric hypertrophy, 21.4 % had concentric remodeling, and 23.2 % had concentric hypertrophy. White matter disease volume was highest in patients with concentric hypertrophy and concentric remodeling, compared to eccentric hypertrophy and normal morphology with a trend-P value of 0.028. Patients with higher relative wall thickness had higher white matter disease volume (10.73 ± 10.29 cc vs 5.89 ± 6.46 cc, P = 0.003), compared to those with normal relative wall thickness. CONCLUSION: Our results showed that abnormal left ventricular geometry is associated with higher white matter disease burden, particularly among those with abnormal relative wall thickness. Future studies are needed to explore causative relationships and potential therapeutic options that may mediate the adverse left ventricular remodeling and its effect in slowing white matter disease progression.

Seasonal shifts in gut microbiota and cold tolerance metrics in a northern population of Reticulitermes flavipes (Blattodea: Rhinotermitidae).

Eastern subterranean termites, Reticulitermes flavipes (Kollar), are widely distributed across North America where they are exposed to a broad range of environmental conditions. However, mechanisms for overwintering are not well understood. Wisconsin is a unique location to study mechanisms of cold tolerance as it represents the northern boundary for persistent R. flavipes populations. In this study, we evaluated seasonal shifts in cold tolerance using critical thermal minimum (CTmin) and supercooling point (SCP) and examined how these measurements correlate to changes in the microbial community of the termite gut. Results showed seasonal acclimatization to cold, which is consistent with the use of behavioral freeze-avoidant mechanisms. However, these insects also demonstrated an increased susceptibility to freezing later in the season, which may be tied to changes in gut microbiota. Our results found shifts in the composition of the gut microbiome in R. flavipes between mid- to late summer and early to late fall. These differences may be suggestive of a change in metabolism to adjust to a period of reduced feeding and increased metabolic stress during overwintering. Specifically, results showed an increased abundance of Methanobrevibacter sp. (Euryarchaeota) associated with cold, which may be indicative of a metabolic shift from acetogenesis to methanogenesis associated with overwintering. Further work is needed focusing on specific contributions of certain gut microbes, particularly their role in metabolic adaptability and in providing protection from oxidative stress associated with changes in environmental conditions.

CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy.

Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFß. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

Improving undergraduate students' email etiquette with computer-based instruction.

Email etiquette is an important skill, especially in professional settings. Research demonstrates that undergraduate students follow email rules when given written instructions plus an example. The purpose of the present study was to evaluate the effects of computer-based email instruction on undergraduate students' email etiquette and to assess the social validity of that instruction. The email instruction package was delivered through an online learning management system and consisted of written instructions plus a model, a quiz, and quiz feedback. We measured email etiquette by scoring emails from course assignments using a checklist. The instruction package produced a replicated increase in mean email checklist scores across two sections of introductory psychology, and checklist scores were elevated when participants sent emails in a novel context. The results of the social-validity assessments suggest that the goals were important, the procedures were acceptable, and there were meaningful improvements in email etiquette for some participants.

Cold temperatures drive the latitudinal range limits and inhibit overwintering survival of the redbanded stink bug (Hemiptera: Pentatomidae).

For non-native insects that are economically damaging, understanding the drivers of range expansions and contractions is important for forecasting pest pressure. The invasion of the redbanded stink bug, Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae), reached Louisiana, United States, in 2000, after which the northern range limits of this species have fluctuated annually. Low winter temperatures have been implicated as a major driver of this pattern, but the importance of cold temperatures-or other abiotic factors-for the persistence of this pest over large geographic scales are incompletely understood. We coupled occurrence data of P. guildinii with climatic data to investigate trends in P. guildinii presence in relation to winter temperatures and develop species distribution models, forecasting habitat suitability based on current and future climatic scenarios. Our results show that (i) some P. guildinii persisted in locations where ambient temperatures reached -12°C, (ii) overwintering temperatures drive P. guildinii range dynamics, and (iii) with intermediate projections of climatic warming, northward expansion by P. guildinii in North America is likely to be minimal. While the northern extent of P. guildinii's range may now be largely realized in North America, our results suggest that increased frequency of mild winters could reduce interannual fluctuations of P. guildinii and enable it to become a more consistent economic concern for soybean growers throughout the Midsouth region of the United States.

Conjugal Synucleinopathies: A Clinicopathologic Study.

BACKGROUND: While preclinical studies have shown that alpha-synuclein can spread through cell-to-cell transmission whether it can be transmitted between humans is unknown. OBJECTIVES: The aim was to assess the presence of a synucleinopathy in autopsied conjugal couples. METHODS: Neuropathological findings in conjugal couples were categorized as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease with Lewy bodies (ADLB), incidental Lewy body disease (ILBD), or no Lewy bodies. RESULTS: Ninety conjugal couples were included; the mean age of death was 88.3 years; 32 couples had no Lewy bodies; 42 couples had 1 spouse with a synucleinopathy: 10 PD, 3 DLB, 13 ADLB, and 16 ILBD; 16 couples had both spouses with a synucleinopathy: in 4 couples both spouses had PD, 1 couple had PD and DLB, 4 couples had PD and ADLB, 2 couples had PD and ILBD, 1 couple had DLB and ADLB, in 3 couples both had ADLB, and 1 couple had ADLB and ILBD. No couples had both spouses with ILBD. CONCLUSIONS: This large series of 90 autopsied conjugal couples found 16 conjugal couples with synucleinopathies, suggesting transmission of synucleinopathy between spouses is unlikely. © 2024 International Parkinson and Movement Disorder Society.

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Morphology of Microchips in the Surface Finishing Process Utilizing Abrasive Films.

In this study, the surface of new lapping films was analyzed, and the lapping finishing process was applied to RG7 tin bronze alloy. The research focused on examining lapping films with electrocorundum grains of nominal sizes 30, 12, and 9 µm, commonly used for achieving smooth surfaces. The manufacturing process involves placing abrasive grains and binder onto a polyester tape, resulting in a heterogeneous distribution of abrasive grains. The study investigates the impact of this random distribution on the performance of lapping films during material removal. Scanning electron microscopy was used to analyze the surface structure of abrasive films, revealing distinctive structures formed by the specific aggregation of abrasive grains. This study explores the influence of different nominal grain sizes on surface finish and aims to optimize lapping processes for diverse applications. The research also delves into microchip analysis, examining the products of the lapping film finishing process. Microchips were observed directly on the abrasive tool surface, revealing insights into their morphology and distribution. The chip segmentation frequency was determined, and they amounted to approximately 0.8 to 3 MHz; these are very high frequencies, which are unique for known chip-forming processes.

Effects of Nontraditional Division III Lacrosse Participation on Movement Pattern Quality and Dynamic Postural Control.

Background/Purpose: No studies have observed the effects of a collegiate lacrosse season on movement pattern quality, dynamic postural control, or the accuracy of athletes' perceived movement pattern quality. The purpose was to examine the effects of a nontraditional fall season on movement pattern quality, perceived movement pattern quality, and dynamic postural control in collegiate lacrosse athletes. Design: Cross-sectional laboratory study. Methods: Fifty men's (age=19.38±1.24 years, height=182.63±6.16 cm, mass=82.37±8.46 kg) and 22 women's (age=19.68±1.17 years, height=165.10±6.88 cm, mass=64.09±8.72 kg) lacrosse players were recruited. Outcome measures included individual Functional Movement Screen™ (FMS™) scores, self-reported perceived movement pattern quality scores, lower and upper extremity Y-Balance Test (YBT) measurements, and active dorsiflexion range of motion (ROM) before the start and again at the end of the fall lacrosse season. Pre- and post-season measurements were assessed using paired t-tests and chi-squared analyses. Results: FMS™ composite scores did not significantly change from preseason to postseason for males (p=0.74) or females (p=0.07). Male perceived movement pattern quality was significantly higher than measured for 10 of 12 movements (p<0.05). Female perceived movement pattern quality was significantly higher than measured for four of 12 movements (p<0.05). Asymmetry frequency significantly increased in males in the hurdle step from two individuals to nine (χ21=25.52, p<0.01), inline lunge from 10 to 20 (χ21=12.50, p<0.01), and shoulder mobility from 4 to 21 (χ21=78.53, p<0.01). Asymmetries in male athletes significantly decreased in the active straight leg raise from 26 to 8 (χ21=25.96, p<0.01). YBT composite scores increased in males for the right leg (p=0.001) and left leg (p<0.03). Right dorsiflexion ROM (p<0.001) and left dorsiflexion ROM (p<0.001) significantly decreased in males from preseason to postseason. YBT scores for the right leg significantly increased in females from preseason to postseason (p=0.01). YBT scores for females for the right arm significantly increased from preseason to postseason (p=0.045). Conclusions: A 5-week season may not change overall movement pattern quality of men's or women's lacrosse players, but some individual movement scores diminished. Athletes may overestimate self-reported movement pattern quality and are therefore unlikely to individually address movement deficits. Male dynamic postural control may change throughout a season, resulting in a potential increased risk of injury later in the season due to compensatory patterns or changes in mobility, proprioception, or balance. Level of Evidence: 3b.

Teacher-student collaborated multiple instance learning for pan-cancer PDL1 expression prediction from histopathology slides.

Programmed cell death ligand 1 (PDL1), as an important biomarker, is quantified by immunohistochemistry (IHC) with few established histopathological patterns. Deep learning aids in histopathological assessment, yet heterogeneity and lacking spatially resolved annotations challenge precise analysis. Here, we present a weakly supervised learning approach using bulk RNA sequencing for PDL1 expression prediction from hematoxylin and eosin (H&E) slides. Our method extends the multiple instance learning paradigm with the teacher-student framework, which assigns dynamic pseudo-labels for intra-slide heterogeneity and retrieves unlabeled instances using temporal ensemble model distillation. The approach, evaluated on 12,299 slides across 20 solid tumor types, achieves a weighted average area under the curve of 0.83 on fresh-frozen and 0.74 on formalin-fixed specimens for 9 tumors with PDL1 as an established biomarker. Our method predicts PDL1 expression patterns, validated by IHC on 20 slides, offering insights into histologies relevant to PDL1. This demonstrates the potential of deep learning in identifying diverse histological patterns for molecular changes from H&E images.