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Abstract Objective Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult‐onset limb‐girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging. Methods In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA‐sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA‐sequencing data was retrieved from ENCODE. Results We generated new RNA‐seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case. Interpretation This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.

Abstract Objective With potential therapies for many forms of Charcot‐Marie‐Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A). Methods 22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1‐year interval. Intramuscular fat fraction (FF) was evaluated using three‐point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT‐HI and plasma neurofilament light chain. Results All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = −0.481; p

Abstract Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage‐induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4‐fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and growth of a charismatic mega moth (Anthereae polyphemus). This work suggests that changes to the phytochemical landscape of forests, mediated by invasive outbreak insects, are likely to negatively impact native insects, with potential repercussions for community diversity and ecosystem function across expansive scales.

Abstract Singlet‐to‐triplet intersystem crossing (ISC) in organic molecules is intimately connected with their geometries: by modifying the molecular shape, symmetry selection rules pertaining to spin‐orbit coupling can be partially relieved, leading to extra matrix elements for increased ISC. As an analog to this molecular design concept, the study finds that the lattice symmetry of supramolecular polymers also defines their triplet formation efficiencies. A supramolecular polymer self‐assembled from weakly interacting molecules is considered. Its 2D oblique unit cell effectively renders it as a coplanar array of 1D molecular columns weakly bound to each other. Using momentum‐resolved photoluminescence imaging in combination with Monte Carlo simulations, the study found that photogenerated charge carriers in the supramolecular polymer predominantly recombine as spin‐uncorrelated carrier pairs through inter‐column charge transfer states. This lattice‐defined recombination pathway leads to a substantial triplet formation efficiency (≈60%) in the supramolecular polymer. These findings suggest that lattice symmetry of micro‐/macroscopic structures relying on intermolecular interactions can be strategized for controlled triplet formation.

Abstract Purpose Real world evidence is crucial to understanding the diffusion of new oncologic therapies, monitoring cancer outcomes, and detecting unexpected toxicities. In practice, real world evidence is challenging to collect rapidly and comprehensively, often requiring expensive and time‐consuming manual case‐finding and annotation of clinical text. In this Review, we summarise recent developments in the use of artificial intelligence to collect and analyze real world evidence in oncology. Methods We performed a narrative review of the major current trends and recent literature in artificial intelligence applications in oncology. Results Artificial intelligence (AI) approaches are increasingly used to efficiently phenotype patients and tumors at large scale. These tools also may provide novel biological insights and improve risk prediction through multimodal integration of radiographic, pathological, and genomic datasets. Custom language processing pipelines and large language models hold great promise for clinical prediction and phenotyping. Conclusions Despite rapid advances, continued progress in computation, generalizability, interpretability, and reliability as well as prospective validation are needed to integrate AI approaches into routine clinical care and real‐time monitoring of novel therapies.

Abstract Science has a history of excluding marginalized groups, including people who are lesbian, gay, bisexual, trans, queer, and other marginalized gender and sexual identities (LGBTQ+), and recent calls urge the wildlife sciences to address disparities. Literature on inclusion in the life sciences generally has focused on personal affirmation and has neglected comprehensive discussion of barriers rooted in historical, structural, and sociocultural context. In our literature review, we construct a narrative highlighting the intersections between historic LGBTQ+ exclusion in society and wildlife science due to current policy trends, pressures of cis‐heteronormativity, and survival barriers on LGBTQ+ people in wildlife sciences in the United States. Wildlife scientists must have competency on LGBTQ+ marginalization topics to advance inclusion in our discipline, and this should include comprehension of historic and current legislation and social perceptions. To bolster inclusion efforts, we recommend thoughtful data collection on experiences of LGBTQ+ people within the wildlife sciences. To address root causes of exclusion, institutions and organizations should address disparities in financial support, housing, and physical and mental health resources as part of LGBTQ+ advocacy, in addition to interpersonal efforts.

Abstract The elevations of water surfaces hold important information on the earth's oceans and land surface waters. Ocean sea surface height is related to the internal change of the ocean's density and mass associated with ocean circulation and its response to climate change. The flow rates of rivers and volume changes of lakes are crucial to freshwater supplies and the hazards of floods and drought resulting from extreme weather and climate events. The Surface Water and Ocean Topography (SWOT) Mission is a new satellite using advanced radar technology to make headway in observing the variability of the elevation of water surfaces globally, providing fundamentally new information previously not available to the study of earth's waters. Here, we provide the first results of SWOT over oceans, rivers, and lakes. We demonstrate the potential of the mission to address science questions in oceanography and hydrology.

Abstract Background The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha‐glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within‐trial medical resource use and costs, and quality‐adjusted life years (QALYs). Methods Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health‐related quality of life was captured using the EuroQol‐5 Dimension‐3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Results Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p = .009), but there were no significant differences in total inpatient days (rate ratio 1.04, p = .30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p

Background One‐time assessment of the Society for Cardiovascular Angiography and Interventions (SCAI) shock classification robustly predicts mortality in the cardiac intensive care unit (CICU). We sought to determine whether serial SCAI shock classification could improve risk stratification. Methods and Results Unique admissions to a single academic level 1 CICU from 2015 to 2018 were included in this retrospective cohort study. Electronic health record data were used to assign the SCAI shock stage during 4‐hour blocks of the first 24 hours of CICU admission. Shock was defined as hypoperfusion (SCAI shock stage C, D, or E). In‐hospital death was evaluated using logistic regression. Among 2918 unique CICU patients, 1537 (52.7%) met criteria for shock during ≥1 block, and 266 (9.1%) died in the hospital. The SCAI shock stage on admission was: A, 37.6%; B, 31.5%; C, 25.9%; D, 1.8%; and E, 3.3%. Patients who met SCAI criteria for shock on admission (first 4 hours) and those with worsening SCAI shock stage after admission were at higher risk for in‐hospital death. Each higher admission (adjusted odds ratio, 1.36 [95% CI, 1.18–1.56]; area under the receiver operating characteristic curve, 0.70), maximum (adjusted odds ratio, 1.59 [95% CI, 1.37–1.85]; area under the receiver operating characteristic curve, 0.73) and mean (adjusted odds ratio, 2.42 [95% CI, 1.99–2.95]; area under the receiver operating characteristic curve, 0.78) SCAI shock stage was incrementally associated with a higher in‐hospital mortality rate. Discrimination was highest for the mean SCAI shock stage (P

Abstract Background Plantar fasciitis is the most commonly reported cause of chronic pain beneath the heel. Management of this condition commonly involves the use of corticosteroid injection in cases where less invasive treatments have failed. However, despite widespread use, only two randomised trials have tested the effect of this treatment in comparison to placebo. These trials currently offer the best available evidence by which to guide clinical practice, though both were limited by methodological issues such as insufficient statistical power. Therefore, the aim of this randomised trial is to compare the effect of ultrasound-guided corticosteroid injection versus placebo for treatment of plantar fasciitis. Methods The trial will be conducted at the La Trobe University Podiatry Clinic and will recruit 80 community-dwelling participants. Diagnostic ultrasound will be used to diagnose plantar fasciitis and participants will be required to meet a range of selection criteria. Participants will be randomly allocated to one of two treatment arms: (i) ultrasound-guided injection of the plantar fascia with 1 mL of 4 mg/mL dexamethasone sodium phosphate (experimental group), or (ii) ultrasound-guided injection of the plantar fascia with 1 mL normal saline (control group). Blinding will be applied to participants and the investigator performing procedures, measuring outcomes and analysing data. Primary outcomes will be pain measured by the Foot Health Status Questionnaire and plantar fascia thickness measured by ultrasound at 4, 8 and 12 weeks. All data analyses will be conducted on an intention-to-treat basis. Conclusion This will be a randomised trial investigating the effect of dexamethasone injection on pre-specified treatment outcomes in people with plantar fasciitis. Within the parameters of this protocol, the trial findings will be used to make evidence-based recommendations regarding the use of corticosteroid injection for treatment of this condition. Trial Registration Australian New Zealand Clinical Trials Registry. ACTRN12610000239066.