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Background: Cancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort. Methods: The authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke. Results: Of 15,454 Australian and US ASPREE participants, 1392 had an incident cancer diagnosis. Rates of CVD were greater in the cancer risk‐set compared to the cancer‐free risk‐set (20.8 vs. 10.3 events per 1000 person‐years; incidence rate ratio, 2.03; 95% confidence interval, 1.51–2.66), with increased incidence seen across MI, HHF, overall stroke, and ischemic stroke. Increased incidence remained after adjustment for clinically significant risk factors for CVD. Incidence was greatest in metastatic, hematological, and lung cancer. Chemotherapy was associated with increased risk of CVD. Similar rates of CVD were seen across aspirin and placebo groups. Conclusions: Incidence of CVD, including MI, HHF, and ischemic stroke, was increased in older adults with cancer. Aspirin did not impact CVD incidence. Risk may be higher in those with metastatic, hematological, and lung cancer, and following chemotherapy. Cancer and its treatment may predispose patients to cardiovascular disease. In the study, the authors demonstrated increased risk of cardiovascular disease in older adults with cancer, particularly following chemotherapy. [ABSTRACT FROM AUTHOR]

Triplet–triplet annihilation (TTA), or triplet fusion, is a biexcitonic process in which two triplet‐excited molecules can combine their energy to promote one into an excited singlet state. To alleviate the dependence of the TTA rate and yield on triplet diffusion in both solid and solution environments, intramolecular TTA (intra‐TTA) has been recently proposed in conjugated molecular systems able to hold multiple triplet excitons simultaneously. Developing from the previous demonstration of TTA performance enhancement in sensitized upconversion solutions, here similar improvements in triplet harvesting in solid‐state films are reported under electrical excitation in organic light emitting diodes (OLEDs). At low dye concentration and low current densities, the intra‐TTA active OLED shows a +40% improved external quantum efficiency with respect to the reference device, and a TTA spin‐statistical factor f 4DPA of 0.4, close to that determined in fluid solution for the individual chromophore (0.45). These results therefore indicate the utility of this molecular design strategy across a wider range of TTA applications, and with particular utility in the further development of low‐power TTA‐enhanced OLEDs. [ABSTRACT FROM AUTHOR]

The objective of this study is to report the long‐term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event‐free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre‐specified groups. Two hundred and twenty‐two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8‐year EFS was 75% (95% confidence interval: 69%–83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow‐up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post‐chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Population genomics has great potential to inform applied conservation management and associated policy. However, the bioinformatic analyses and interpretation of population genomic datasets can be daunting and difficult to convey to nonspecialists, including on‐the‐ground conservationists that work with many state, federal and international agencies. We think that individual population genomic metrics of interest can be interpolated and ultimately distilled into thematic GIS layers that represent spatiotemporal genomic potential (or conversely, susceptibility) in conservation monitoring. As examples relevant to ongoing conservation efforts, we use introgressive hybridisation and individual heterozygosity to illustrate a conceptual approach for mapping population genomic susceptibility. The general framework of thematic layers could be extended to integrate key genomic metrics (e.g., runs of homozygosity and genomic load) that are relevant to many conservation efforts. [ABSTRACT FROM AUTHOR]

Talc is expected to be an important water carrier in Earth's upper mantle, and understanding its electrical and seismic properties under high pressure and temperature conditions is required to detect possible talc‐rich regions in subduction zones imaged using geophysical observations. We conducted acoustic and electrical experiments on natural talc aggregates at relevant pressure‐temperature conditions. Compressional wave velocity (Vp) was measured using ultrasonic interferometry in a Paris‐Edinburgh press at pressures up to 3.4 GPa and temperatures up to 873 K. Similar Vp values are obtained regardless of the initial crystallographic preferred orientation of the samples, which can be explained by talc grain reorientation during the experiment, with the (001) plane becoming perpendicular to the uniaxial compression axis. Electrical conductivity of the same starting material was determined using impedance spectroscopy in a multi‐anvil press up to 6 GPa and 1263 K. Two conductivity jumps are observed, at ∼860–1025 K and ∼940–1080 K, depending on pressure, and interpreted as talc dehydroxylation and decomposition, respectively. Electrical anisotropy is observed at low temperature and decreases with increasing pressure (∼10 at 1.5 GPa and ∼2 at 3.5 GPa). Comparison of acoustic and electrical results with geophysical observations in central Mexico supports the presence of a talc‐bearing layer atop the subducted Cocos plate. Plain Language Summary: Talc is a mineral that transports water inside the Earth. Understanding its seismic and electrical properties is important to detect its presence at depth and to follow the water cycle. In this study, we measured these two physical properties on a talc rock at relevant temperature and pressure conditions. We observe that the seismic velocities can be >0.8 km/s slower than those reported in previous studies, which is caused by grain reorientation in the high‐pressure device. This type of rock deformation can also occur in nature. The electrical response of talc shows two sharp changes at specific temperatures. These changes indicate two transformations in the structure of the mineral. Applied to the field, our experimental findings suggest that a talc‐bearing layer under central Mexico can explain the field (seismic and electrical) observations. Our study shows that the combination of different physical properties is important to understand the deep water cycle in our planet. Key Points: Acoustic and electrical measurements were performed on natural talc aggregates at high pressure and temperature conditionsThe experimental data set was complemented with a series of textural and chemical analyses (electron backscatter diffraction (EBSD), electron microprobe analyses, X‐ray diffraction, Raman spectroscopy)A thin talc‐bearing layer can explain the field seismic and electrical observations atop the subducted Cocos plate below central Mexico [ABSTRACT FROM AUTHOR]

Spring wheat (Triticum aestivum L.) is a popular bread wheat with high milling and baking requirements. Vernalization is not required for spring wheat, which allows for fast growth under manipulated conditions. This experiment's objective was rapid development of inbred lines of hard red spring wheat throughout the off‐season and preserve enough genetic variability to perform selection. A total of 1575 F2 heads from three distinct populations were randomly harvested in the field‐season 2021. To break seed dormancy, seeds were held for 2 days at 0°C. Three breeding cycles were performed through single seed descent under manipulated growth condition during the off‐season 2021–2022. We were able to harvest plant materials as quickly as 54 days after planting in comparison to 110 days average field season. We lost a total of 36.4% during the three off‐season fast advancement generations and 711 genotypes reached the F5:6 generation with enough seed to perform a partially replicated small plot yield trial at two locations during the 2022 field‐season. Response traits collected included grain yield, grain protein, plant height, days to heading, and bacterial leaf streak (Xanthomonas transluens) disease severity. Heritability of collected traits varied between 0.61 and 0.92. Although we had considerable loss during the speed breeding, we were able to identify superior genotypes compared to the parents. Core Ideas: Speed breeding program succeeded in advancing wheat populations from F2 to F5:6 in just one off‐season, achieving a 54‐day harvest cycle.Accelerated inbreeding using Single Seed Descent speeds this process by growing multiple generations in an off‐season, enhancing genetic uniformity rapidly.Despite loss, 711 genotypes reached F5:6, allowing field trials for yield and traits. Plain Language Summary: Spring wheat is a type of bread wheat that does not need long, cold temperatures to grow, making it good for quick growth. In this study, the goal was to rapidly develop new inbred lines of wheat while keeping enough genetic diversity for selection. We started with 1575 wheat heads from three different populations in 2021 and used a method called single seed descent to speed up breeding. By controlling the growth environment manipulating light and temperature, we shortened the usual 110‐day growing season to just 54 days. Despite losing 36.4% of the plants, we successfully advanced 711 genotypes. These were then tested in small field plots in 2022 in two locations. The traits we measured included grain yield, protein content, plant height, heading time, and resistance to the disease called bacterial leaf streak. We were able to reduce the growth cycle and even with some losses, we identified promising new genotypes that outperformed their parent plants. [ABSTRACT FROM AUTHOR]

VMXm joins the suite of operational macromolecular crystallography beamlines at Diamond Light Source. It has been designed to optimize rotation data collections from protein crystals less than 10 µm and down to below 1 µm in size. The beamline has a fully focused beam of 0.3 × 2.3 µm (vertical × horizontal) with a tuneable energy range (6–28 keV) and high flux (1.6 × 1012 photons s−1 at 12.5 keV). The crystals are housed within a vacuum chamber to minimize background scatter from air. Crystals are plunge‐cooled on cryo‐electron microscopy grids, allowing much of the liquid surrounding the crystals to be removed. These factors improve the signal‐to‐noise during data collection and the lifetime of the microcrystals can be prolonged by exploiting photoelectron escape. A novel in vacuo sample environment has been designed which also houses a scanning electron microscope to aid with sample visualization. This combination of features at VMXm allows measurements at the physical limits of X‐ray crystallography on biomacromolecules to be explored and exploited. [ABSTRACT FROM AUTHOR]

Background and Purpose: Spinal cord stimulation (SCS) is approved by the Food and Drug Administration for treating chronic intractable pain in the back, trunk, or limbs through stimulation of the dorsal column. Numerous studies have used swine as an analog of the human spinal cord to better understand SCS and further improve its efficacy. We performed high‐resolution imaging of the porcine spinal cord with intact dura mater using micro‐computed tomography (μCT) to construct detailed 3‐dimensional (3D) visualizations of the spinal cord and characterize the morphology of the dorsal and ventral rootlets. Methods: We obtained spinal cords from Yorkshire/Landrace crossbred swine (N = 7), stained samples with osmium tetroxide, and performed μCT imaging of the T12‐T15 levels at isotropic voxel resolutions ranging from 3.3 to 50 μm. We measured the anatomical morphology using the 3D volumes and compared our results to measurements previously collected from swine and human spinal cords via microdissection techniques in prior literature. Results: While the porcine thoracic‐lumbar spinal cord is a popular model for SCS, we highlight multiple notable differences compared to previously published T8‐T12 human measurements including rootlet counts (porcine dorsal/ventral: 12.2 ± 2.6, 26.6 ± 3.4; human dorsal/ventral: 5.3 ± 1.3, 4.4 ± 2.4), rootlet angles (porcine ventral‐rostral: 161 ± 1°, ventral‐caudal: 155 ± 6°, dorsal‐rostral: 148 ± 9°, dorsal‐caudal: 142 ± 6°; human ventral‐rostral: 170 ± 3°, ventral‐caudal: 22 ± 10°, dorsal‐rostral: 171 ± 3°, dorsal‐caudal: 15 ± 7°), and the presence and count of dorsal rootlet bundles. Conclusions: Detailed measurements and highlighted differences between human and porcine spinal cords can inform variations in modeling and electrophysiological experiments between the two species. In contrast to other approaches for measuring the spinal cord and rootlet morphology, our method keeps the dura intact, reducing potential artifacts from dissection. [ABSTRACT FROM AUTHOR]

Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant‐producing cells and lower surfactant‐protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P < 0.001), but not SFTPC (P = 0.177) or SFTPD (P = 0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P = 0.007), dynamic lung compliance (P < 0.001), and SFTPA (P = 0.037) and SFTPB gene expression (P = 0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near‐term neonates, even in the absence of impairment by maternal asthma. What is the central question of this study?Does antenatal betamethasone before near‐term delivery mitigate the increased risk of neonatal lung disease in a sheep model of maternal asthma?What is the main finding and its importance?Maternal asthma did not impair neonatal lung function or reduce surfactant gene expression, likely reflecting a mild maternal and fetal phenotype in this cohort. Nevertheless, antenatal maternal betamethasone treatment in asthmatic pregnancies increased dynamic lung compliance and surfactant protein A and B mRNA expression in newborn lambs. These data suggest potential benefits of betamethasone on lung maturation when mothers have asthma. [ABSTRACT FROM AUTHOR]

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34 ± 10 years, 7 males) completed three visits: visits 1 and 2 included non‐invasive normoxic (fraction of inspired oxygen (FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$) = 0.21) and isobaric hypoxic (FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ = 0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake (V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan–Ganz or conductance catheterization to quantify RV performance via pressure–volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ and again at 50% hypoxic V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ (FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ = 0.12). Median (interquartile range) values for non‐invasive V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P < 0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P = 0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax, and end‐systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular–arterial coupling was maintained during normoxic exercise at 50% V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$. During submaximal exercise at 50% of hypoxic V̇O2max${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$, ventricular–arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ = 0.12 and the associated increase in PA pressures. Key points: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions.During submaximal exercise, ventricular–arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained.These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure. [ABSTRACT FROM AUTHOR]

Breathing mild bouts of low oxygen air (i.e. acute intermittent hypoxia, AIH) has been shown to improve locomotor function in humans after a spinal cord injury. How AIH‐induced gains in motor performance are achieved remains unclear. We examined the hypothesis that AIH augments motor learning and motor retention during a locomotor adaptation task. We further hypothesized that gains in motor learning and retention will be associated with reductions in net metabolic power, consistent with the acquisition of energetically favourable mechanics. Thirty healthy individuals were randomly allocated into either a control group or an AIH group. We utilized a split‐belt treadmill to characterize adaptations to an unexpected belt speed perturbation of equal magnitude during an initial exposure and a second exposure. Adaptation was characterized by changes in spatiotemporal step asymmetry, anterior–posterior force asymmetry, and net metabolic power. While both groups adapted by reducing spatial asymmetry, only the AIH group achieved significant reductions in double support time asymmetry and propulsive force asymmetry during both the initial and the second exposures to the belt speed perturbation. Net metabolic power was also significantly lower in the AIH group, with significant reductions from the initial perturbation exposure to the second. These results provide the first evidence that AIH mediates improvements in both motor learning and retention. Further, our results suggest that reductions in net metabolic power continue to be optimized upon subsequent learning and are driven by more energetically favourable temporal coordination strategies. Our observation that AIH facilitates motor learning and retention can be leveraged to design rehabilitation interventions that promote functional recovery. Key points: Brief exposures to low oxygen air, known as acute intermittent hypoxia (AIH), improves locomotor function in humans after a spinal cord injury, but it remains unclear how gains in motor performance are achieved.In this study, we tested the hypothesis that AIH induces enhancements in motor learning and retention by quantifying changes in interlimb coordination, anterior–posterior force symmetry and metabolic cost during a locomotor adaptation task.We show the first evidence that AIH improves both motor learning and savings of newly learned temporal interlimb coordination strategies and force asymmetry compared to untreated individuals.We further demonstrate that AIH elicits greater reductions in metabolic cost during motor learning that continues to be optimized upon subsequent learning.Our findings suggest that AIH‐induced gains in locomotor performance are facilitated by enhancements in motor learning and retention of more energetically favourable coordination strategies. [ABSTRACT FROM AUTHOR]

The article delves into the reconsideration of leukoreduction of whole blood for patients facing life-threatening hemorrhage, particularly in trauma centers and military blood programs. It examines the benefits and limitations of leukoreduction in reducing febrile reactions, CMV transmission, and HLA alloimmunization, as well as the operational challenges and benefits. The text also compares the use of leukoreduced (LR) and non-LR whole blood for transfusion purposes, highlighting cost implications, shelf life differences, and the need for further clinical trials to determine effects on patient outcomes. The article underscores the importance of carefully weighing the potential benefits and risks of using LR versus non-LR whole blood in clinical decision-making for patients with major bleeding. [Extracted from the article]

Background: Healthcare systems globally face the issue of resource constraints and need for prioritization of elective surgery. Inclusive, explicit prioritization tools are important in improving consistency and equity of access to surgery across health systems. The General Surgical Prioritization Tool developed by New Zealand's Ministry of Health scores patients for elective non‐cancer surgery based on surgeon's clinical judgement and patient derived Impact on Life (IoL) scores. This study aims to measure the changes in patient derived IoL scores after common general surgical procedures to enable direct comparison and inform future prioritization. Method: This longitudinal observational study enrolled 322 participants who had undergone elective general surgical procedures. Participants were contacted 3 to 9 months after their procedures and requested to complete the IoL questionnaire. The primary endpoint was the change in IoL scores after surgery among the different procedures. Results: Overall, 229/304 (75%) participants responded to the questionnaire and there were no significant baseline differences between responders and non‐responders. Patients in the gallbladder treatment group had the greatest improvement in IoL scores. Patients across all ethnic groups had similar changes in IoL scores. Multivariate analysis showed that gallbladder surgery (relative to hernia surgery) and pre‐surgery IoL scores significantly predicted improvement. Conclusion: The patient reported IoL score recorded at prioritization for surgery all reduced, albeit to varying amounts, after common general surgical procedures. This, combined with the fact that IoL scores predicted post‐operative improvement support their inclusion in prioritization tools in addition to surgeon derived components. [ABSTRACT FROM AUTHOR]

Due to widespread atmospheric deposition of mercury (Hg), all aquatic food webs are contaminated with toxic methyl mercury (MeHg). At high concentrations, MeHg poses a health hazard to wildlife and humans. Spiders feeding in riparian habitats (hereafter referred to as riparian spiders) have been proposed as sentinels of MeHg contamination of aquatic systems. Riparian spiders are exposed to MeHg through their diets, and the concentration of MeHg in spiders is positively related to the proportion of MeHg‐contaminated emergent aquatic insects in their diets. The use of spiders as sentinels is complex because their MeHg concentrations can vary, not only among ecosystems but also between different spider taxa and as a function of spider body size. The objective of the present study was to examine how the level of ecosystem contamination, spider taxon, and spider body size interact to influence MeHg concentrations in four genera of riparian spiders from two rivers with different levels of Hg contamination. We collected four genera of riparian spiders (Tetragnatha sp., Larinioides sp., Pardosa sp., and Rabidosa sp.) from two sites along both the Clear Fork of the Trinity River and the West Fork of the Trinity River (Fort Worth, TX, USA). We analyzed concentrations of MeHg in different body sizes of spiders from each genus. We found that MeHg contamination of the river ecosystem, spider taxon, and spider body size were important determinants of MeHg concentration in riparian spiders. The results suggest that any of the four taxa of riparian spiders from the present study could be used as sentinels of aquatic MeHg contamination, but they should not be used interchangeably because of the interdependence between the effects of ecosystem contamination level, spider taxon, and body size. Future studies utilizing riparian spiders as sentinels of biomagnifying aquatic contaminants (e.g., MeHg, polychlorinated biphenyls) should consider the potentially complex interaction effects between ecosystem contamination level, spider taxon, and spider body size. Environ Toxicol Chem 2024;43:2169–2175. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Pushing selected information to clinicians, as opposed to the traditional method of clinicians pulling information from an electronic medical record, has the potential to improve care. A digital notification platform was designed by clinicians and implemented in a tertiary hospital to flag dysglycaemia. There were 112 patients included in the study, and the post‐implementation group demonstrated lower rates of dysglycaemia (2.5% vs 1.1%, P = 0.038). These findings raise considerations for information delivery methods for multiple domains in contemporary healthcare. [ABSTRACT FROM AUTHOR]

WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell‐types in the glomerulus. We hypothesised that this could be resolved using single‐cell RNA sequencing (scRNA‐seq) and ligand‐receptor analysis to profile glomerular cell–cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1R394W/+). Podocytes were the most dysregulated cell‐type in the early stages of Wt1R394W/+ disease, with disrupted angiogenic signalling between podocytes and the endothelium, including the significant downregulation of transcripts for the vascular factors Vegfa and Nrp1. These signalling changes preceded glomerular endothelial cell loss in advancing disease, a feature also observed in biopsy samples from human WT1 glomerulopathies. Addition of conditioned medium from murine Wt1R394W/+ primary podocytes to wild‐type glomerular endothelial cells resulted in impaired endothelial looping and reduced vascular complexity. Despite the loss of key angiogenic molecules in Wt1R394W/+ podocytes, the pro‐vascular molecule adrenomedullin was upregulated in Wt1R394W/+ podocytes and plasma and its further administration was able to rescue the impaired looping observed when glomerular endothelium was exposed to Wt1R394W/+ podocyte medium. In comparative analyses, adrenomedullin upregulation was part of a common injury signature across multiple murine and human glomerular disease datasets, whilst other gene changes were unique to WT1 disease. Collectively, our study describes a novel role for altered angiogenic signalling in the initiation of WT1 glomerulopathy. We also identify adrenomedullin as a proangiogenic factor, which despite being upregulated in early injury, offers an insufficient protective response due to the wider milieu of dampened vascular signalling that results in endothelial cell loss in later disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Objective: Although olfactory dysfunction is one of the most common presenting signs of COVID‐19 infection, little is known about which populations are most susceptible. The aim of this study is to evaluate the risk of COVID‐19‐induced chemosensory dysfunction in malnourished individuals. Methods: The N3C database was queried for adults having positive COVID‐19 test result, diagnosis of chemosensory dysfunction within 2 weeks of positive test date, and overnutrition or undernutrition (i.e., deficiency or excess of micro‐ and macronutrients) related diagnoses prior to COVID‐19 infection. Individuals previously diagnosed with chemosensory dysfunction were excluded. COVID‐19‐positive adults without olfactory dysfunction were similarly analyzed. Statistical analysis was performed using odds ratio calculations (95% confidence interval [CI]). Results: Of 3,971,536 patients with COVID‐19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.0647, 0.0825]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.419 (p < 0.0001, 95% CI [1.3359, 1.5081]). Conclusion: Overnutrition may increase the risk of COVID‐19‐related olfactory dysfunction, while undernutrition may slightly protect. While reasons are unclear, baseline differences in metabolic, inflammatory, and structural biochemistry deserve closer inspection. Level of Evidence: 3 Laryngoscope, 134:4338–4343, 2024 [ABSTRACT FROM AUTHOR]

Summary: Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with 'triple‐negative thrombocytosis', we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology ('myeloproliferative neoplasm‐definite/probable', 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real‐world 'triple‐negative' ET diagnosis currently depends heavily on histology; we advocate caution in MGP‐negative cases and that specific guidelines are needed. [ABSTRACT FROM AUTHOR]

Antarctic Bottom Water (AABW) formation and transport constitute a key component of the global ocean circulation. Direct observations suggest that AABW volumes and transport rates may be decreasing, but these observations are too temporally or spatially sparse to determine the cause. To address this problem, we develop a new method to reconstruct AABW transport variability using data from the GRACE (Gravity Recovery and Climate Experiment) satellite mission. We use an ocean general circulation model to investigate the relationship between ocean bottom pressure and AABW: we calculate both of these quantities in the model, and link them using a regularized linear regression. Our reconstruction from modeled ocean bottom pressure can capture 65%–90% of modeled AABW transport variability, depending on the ocean basin. When realistic observational uncertainty values are added to the modeled ocean bottom pressure, the reconstruction can still capture 30%–80% of AABW transport variability. Using the same regression values, the reconstruction skill is within the same range in a second, independent, general circulation model. We conclude that our reconstruction method is not unique to the model in which it was developed and can be applied to GRACE satellite observations of ocean bottom pressure. These advances allow us to create the first global reconstruction of AABW transport variability over the satellite era. Our reconstruction provides information on the interannual variability of AABW transport, but more accurate observations are needed to discern AABW transport trends. Plain Language Summary: Ocean circulation moves heat and carbon around the globe. Changes in the way this circulation moves heat and carbon influence future climate. One part of this ocean circulation is Antarctic Bottom Water, which forms around Antarctica and flows north along the ocean floor into the Pacific, Atlantic and Indian Oceans. Observations of Antarctic Bottom Water are sparse. Those which exist suggest that the volume of Antarctic Bottom Water is declining, but are insufficient to explain why this is happening. We design a new method to try and measure Antarctic Bottom Water transport. The physical equations describing fluid flows suggest gravity signals measured by satellites might be useful. To establish how useful this data is, we simulate the observations of these satellites in an ocean model. We also calculate the transport of Antarctic Bottom Water in the model. This means we can investigate how effective the modeled satellite data is at measuring modeled Antarctic Bottom Water. Our method of using the satellite data skilfully measures Antarctic Bottom Water transport, so we use this method to calculate Antarctic Bottom Water from the real‐world satellite observations. Key Points: We use estimates of ocean bottom pressure from the Gravity Recovery and Climate Experiment (GRACE) satellites as a proxy for Antarctic Bottom Water transportThe largest source of uncertainty in our reconstruction is satellite measurement uncertaintyWe reconstruct Antarctic Bottom Water transport anomalies, capturing an estimated 30%–80% of variance [ABSTRACT FROM AUTHOR]

The capability to anticipate the exceptionally rapid warming of the Northwest Atlantic Shelf and its evolution over the next decade could enable effective mitigation for coastal communities and marine resources. However, global climate models have struggled to accurately predict this warming due to limited resolution; and past regional downscaling efforts focused on multi‐decadal projections, neglecting predictive skill associated with internal variability. We address these gaps with a high resolution (1/12°) ensemble of dynamically downscaled decadal predictions. The downscaled simulations accurately predicted past oceanic variability at scales relevant to marine resource management, with skill typically exceeding global coarse‐resolution predictions. Over the long term, warming of the Shelf is projected to continue; however, we forecast a temporary warming pause in the next decade. This predicted pause is attributed to internal variability associated with a transient, moderate strengthening of the Atlantic meridional overturning circulation and a southward shift of the Gulf Stream. Plain Language Summary: The Northwest Atlantic Shelf is experiencing a rapid rise in ocean temperatures, one of the fastest globally, impacting the region's marine resources. Global coupled models struggle to accurately simulate this regional warming and have large uncertainties associated with the future evolution of this warming. To address this issue, we developed a high‐resolution decadal prediction system for the Northwest Atlantic Shelf which downscales global decadal predictions using a high‐resolution regional ocean model. The downscaled simulations accurately predict past oceanic variability and forecast a temporary pause in warming over the next decade due to natural changes in the Atlantic meridional overturning circulation and the position of the Gulf Stream. This predictive capability could pave the way for the implementation of effective mitigation strategies, benefiting coastal communities and marine resources alike. Key Points: Dynamical downscaling enhances decadal prediction skill of Northwest Atlantic Shelf sea surface temperaturesA temporary respite from rapid Northwest Atlantic Shelf warming is forecast for the coming decadeThe forecast warming pause is attributed to a modest strengthening of the Atlantic meridional overturning circulation [ABSTRACT FROM AUTHOR]

Many international, national, state, and local organizations prioritize the ranking of threatened and endangered species to help direct conservation efforts. For example, the International Union for Conservation of Nature (IUCN) assesses the Green Status of species and publishes the influential Red List of threatened species. Unfortunately, such conservation yardsticks do not explicitly consider genetic or genomic diversity (GD), even though GD is positively associated with contemporary evolutionary fitness, individual viability, and with future evolutionary potential. To test whether populations of genome sequences could help improve conservation assessments, we estimated GD metrics from 82 publicly available mammalian datasets and examined their statistical association with attributes related to conservation. We also considered intrinsic biological factors, including trophic level and body mass, that could impact GD and quantified their relative influences. Our results identify key population GD metrics that are both reflective and predictive of IUCN conservation categories. Specifically, our analyses revealed that Watterson's theta (the population mutation rate) and autozygosity (a product of inbreeding) are associated with the current Red List categorization, likely because demographic declines that lead to "listing" decisions also reduce levels of standing genetic variation. We argue that by virtue of this relationship, conservation organizations like IUCN could leverage emerging genome sequence data to help categorize Red List threat rankings (especially in otherwise data‐deficient species) and/or enhance Green Status assessments to establish a baseline for future population monitoring. Thus, our paper (1) outlines the theoretical and empirical justification for a new GD‐based assessment criterion, (2) provides a bioinformatic pipeline for estimating GD from population genomic data, and (3) suggests an analytical framework that can be used to measure baseline GD while providing quantitative GD context for consideration by conservation authorities. [ABSTRACT FROM AUTHOR]

Background and Objectives: The objective of this study was to evaluate a series of Rapid Visco Analyzer (RVA) methods for their ability to produce results that were predictive of Japanese sponge cake (JSC) quality. Two solvents (water and 50% [w/w] sucrose in water) and two temperature profiles [Standard 1 (STD 1) and an internal cake temperature profile] were selected to run across a diverse set of flour samples from two crop years that possessed variable bake performance. The results were analyzed for predictive outcomes for JSC prepared using a mechanical fold method. Findings: The solvent retention capacity (SRC) results did not show any significant trends with JSC quality. The RVA results from both profiles using water as the solvent did not show a significant correlation with JSC quality while the 50% (w/w) sucrose solvent was significantly correlated (p ≤.01). The STD 1 and internal cake temperature profile batter pasting viscosity (BPV) using the sucrose solvent showed significant (p ≤.01) correlations with mechanical folded JSC volume (r =.97), firmness (r = −.88), and overall score (r =.85). Conclusions: The RVA BPV results showed that a 50% sucrose solvent could more accurately be used to predict and screen for JSC quality outcomes. Both RVA profiles could be used with a sucrose solvent to predict JSC quality. JSC volume and overall score showed significant positive correlations with BPV while firmness had a significant negative correlation. Significance and Novelty: This research identified two RVA profiles that when paired with a 50% (w/w) sucrose solvent could be used to screen for JSC quality using less flour and taking less time than a bake test. This test could potentially assist breeders and millers in quicky screening flours for efficient decision making. This is the first time an RVA temperature profile that mimics the internal rise in temperature for a JSC during baking has been used to predict JSC quality. In addition, the STD 1 profile using the 50% (w/w) sucrose solvent has not been previously used to predict JSC quality. [ABSTRACT FROM AUTHOR]

Background: People with bipolar disorder (BD) tend to show widespread cognitive impairment compared to healthy controls. Impairments in processing speed (PS), attention and executive function (EF) may represent 'core' impairments that have a role in wider cognitive dysfunction. Cognitive impairments appear to relate to structural brain abnormalities in BD, but whether core deficits are related to particular brain regions is unclear and much of the research on brain‐cognition associations is limited by univariate analysis and small samples. Methods: Euthymic BD patients (n = 56) and matched healthy controls (n = 26) underwent T1‐weighted MRI scans and completed neuropsychological tests of PS, attention and EF. We utilised public datasets to develop normative models of cortical thickness (n = 5977) to generate robust estimations of cortical abnormalities in patients. Canonical correlation analysis was used to assess multivariate brain‐cognition associations in BD, controlling for age, sex and premorbid IQ. Results: BD showed impairments on tests of PS, attention and EF, and abnormal cortical thickness in several brain regions compared to healthy controls. Impairments in tests of PS and EF were most strongly associated with cortical thickness in the left inferior temporal, right entorhinal and right temporal pole areas. Conclusion: Impairments in PS, attention and EF can be observed in euthymic BD and may be related to abnormal cortical thickness in temporal regions. Future research should continue to leverage normative modelling and multivariate methods to examine complex brain‐cognition associations in BD. Future research may benefit from exploring covariance between traditional brain structural morphological metrics such as cortical thickness, cortical volume and surface area. [ABSTRACT FROM AUTHOR]

Pembrolizumab has received approval in the UK as first‐line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE‐048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real‐world data on the role of pembrolizumab monotherapy as first‐line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression‐free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6–6.1), and the median OS was 10.8 months (95% CI 9.0–12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune‐related adverse events (irAEs). 53 patients proceeded to second‐line treatment with a median PFS2 of 10.2 months (95% CI: 8.8–11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log‐rank p value = <.001) and median OS (18.8 vs. 8.9 months; log‐rank p value <.001). The efficacy and safety of pembrolizumab first‐line monotherapy for HNSCC has been validated using real‐world data. [ABSTRACT FROM AUTHOR]

The North American craton interior preserves a >1 Ga history of near surface processes that inform ongoing debates regarding timing and drivers of continental‐scale deformation and erosion associated with far‐field orogenesis. We tested various models of structural inversion on a major segment of the Midcontinent Rift along the Douglas Fault (DF) in northern Wisconsin, which accommodated ≳10 km of total vertical displacement. U‐Pb detrital zircon and vein calcite Δ47/U‐Pb thermochronometry from the hanging wall constrain the majority of uplift (≳8.5 km) and deformation to 1052–1036 Ma during the Ottawan phase of the Grenvillian orogeny. Combined U‐Pb zircon dates, Δ47/U‐Pb calcite thermochronometry, and field data that document syn‐ to early post‐depositional deformation in the footwall constrain a second stage of uplift (1–1.5 km) ca. 995–980 Ma during the Rigolet phase of the Grenvillian orogeny. A minor phase of Appalachian far‐field orogenesis is associated with minimal thrust reactivation. Our combined analyses identified the 995–980 Ma Bayfield Group as a Grenvillian foreland basin with an original thickness 0.5–2 km greater than currently preserved. By quantifying flexural loading and other subsidence mechanisms along the Douglas Fault, we identify dynamic subsidence as a mechanism that could be consistent with the development of late‐Grenvillian transcontinental fluvial systems. Minimal post‐Grenvillian erosion (0.5–2 km) in this part of the craton interior has preserved the Bayfield Group and equivalent successions, limiting the magnitude of regional erosion that can be attributed to Neoproterozoic glaciation. Plain Language Summary: Around 1.1 billion years ago, volcanic rocks and sediments began accumulating in a large rift basin around the present‐day Lake Superior region of North America. Continent‐continent collision on the edge of North America caused rifting to cease and major uplift to occur on thrust faults in the rift. The timing of the tectonic shift and the amount of crustal uplift and the number of uplift episodes are all poorly constrained. Our new geochronology precisely identifies the age of two major uplift episodes, ∼1.05 and ∼0.98 billion years ago. Mineral veins that formed during uplift record the age and temperature of formation, which enables reconstruction of an uplift history. We conclude that the collisional event ∼1.05 billion years ago resulted in ≳8.5 km of uplift followed by 1.0–1.5 km of uplift ∼0.98 billion years ago. A sedimentary basin associated with collision ∼1.0 billion years ago may have been part of a vast transcontinental river system. The surface underlying the Great Unconformity, a surface representing missing time, regionally did not undergo much erosion following uplift, suggesting long‐term stability of the North American craton interior over the last ∼0.98 billion years. Key Points: U‐Pb zircon and calcite dates constrain two‐stage Grenvillian inversion of the Midcontinent Rift on the Douglas Fault (DF) in northern WisconsinΔ47/U‐Pb thermochronometry constrains vertical displacement of ≳8.5 and ∼1.5 km in the Ottawan and Rigolet Grenvillian phases, respectivelyBasin analysis and clay mineralogy constrain original thickness, subsidence drivers, and erosion of a ca. 1010–980 Ma Grenvillian foreland [ABSTRACT FROM AUTHOR]

Background: Societal changes have led to greater isolation and higher levels of loneliness particularly for older generations. Loneliness is a significant public health challenge leading to increased levels of poor mental health. Depression and anxiety are also increasing in prevalence amongst children and young people. Intergenerational activities are interventions designed to bring together older and younger generations with the purpose of allowing participants to utilise their experiences and skills, and to give participants a chance to experience the pleasure and excitement that occurs with the transmission of knowledge and skills from one generation to another. Intergenerational activities are therefore potential interventions that can address the growing problems associated with loneliness and lack of wellbeing. Objectives: This systematic review aims to examine the impact of intergenerational interventions on the wellbeing and mental health in children and adolescents, and potential harmful effects. It also aims to identify areas for future research as well as key messages for service commissioners. Search Methods: We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for children and young people. Selection Criteria: Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for children and young people were included in this review. Data Collection and Analysis: We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Main Results: While we identified 500 evaluations of intergenerational interventions, where the impact on participating children and/or young people was evaluated this was most often limited to assessing their impact on attitudes to aging. We identified five studies evaluating five different types of intergenerational interventions which included one‐off sessions to ones that spanned a year measuring their impact on the mental health and wellbeing of children and/or young people. The purposes of the interventions differed, which included promoting social skills, preventing harmful behaviour and promoting learning. The ages of children also varied across the five studies, with one targeting younger children, two targeting younger teenagers and two targeting older teenagers. One study included socioeconomically disadvantaged children, and in the other studies the socioeconomic backgrounds of the children and young people were not described. The outcome measures used to evaluate the interventions varied with none of the studies measuring the same outcomes. One study showed improvements in wellbeing measures, and this was an intervention delivered to children in deprived neighbourhoods, where the intervention duration was for a year allowing the development of a greater depth of relationship between the younger and older participants. Four studies found no....... The included studies were at high risk of bias therefore raising uncertainty in the reliability of the findings. Underpinning theories that supported the development of the interventions and explained the mechanisms of effect were poorly described. Authors' Conclusions: The evidence for the effectiveness of intergenerational interventions on the mental health and wellbeing of children and young people is limited and inconclusive. Few evaluations have sought to measure how intergenerational interventions impact children and young people and where this impact is measured the focus is usually limited to attitudes to aging. The evidence that has been collected is too heterogenous to allow synthesis of the findings. The underpinning theories to support their development are poorly described with no follow‐up data to ascertain if benefits are maintained. Intergenerational interventions show promise but researchers have failed to measure how they impact on the mental health and wellbeing of children and young people. This is a serious limitation of the evidence base that needs to be addressed in robust and rigorous evaluations. [ABSTRACT FROM AUTHOR]

Aim: We test the hypothesis that wind dispersal is more common among emergent tree species given that being tall increases the likelihood of effective seed dispersal. Location: Americas, Africa and the Asia‐Pacific. Time period: 1970–2020. Major taxa studied: Gymnosperms and Angiosperms. Methods: We used a dataset consisting of tree inventories from 2821 plots across three biogeographic regions (Americas, Africa and Asia‐Pacific), including dry and wet forests, to determine the maximum height and dispersal strategy of 5314 tree species. A web search was used to determine whether species were wind‐dispersed. We compared differences in tree species maximum height between biogeographic regions and examined the relationship between species maximum height and wind dispersal using logistic regression. We also tested whether emergent tree species, that is species with at least one individual taller than the 95% height percentile in one or more plots, were disproportionally wind‐dispersed in dry and wet forests within each biogeographic region. Results: Our dataset provides maximum height values for 5314 tree species, of which more than half (2914) had no record of this trait in existing global databases. We found that, on average, tree species in the Americas have lower maximum heights compared to those in Africa and the Asia Pacific. The probability of wind dispersal increased significantly with tree species maximum height and was significantly higher among emergent than non‐emergent tree species in both dry and wet forests in all three biogeographic regions. Main conclusion: Wind dispersal is more prevalent in tall, emergent tree species than in non‐emergent species and may thus be an important factor in the evolution of tree species maximum height. By providing the most comprehensive dataset so far of tree species maximum height and wind dispersal strategies, this study paves the way for advancing our understanding of the eco‐evolutionary drivers of tree size. [ABSTRACT FROM AUTHOR]

Background: The causes for delays during the COVID19 pandemic and their impact on head and neck cancer (HNC) diagnosis and staging are not well described. Methods: Two cohorts were defined a priori for review and analysis—a Pre‐Pandemic cohort (June 1 to December 31, 2019) and a Pandemic cohort (June 1 to December 31, 2020). Delays were categorized as COVID‐19 related or not, and as clinician, patient, or policy related. Results: A total of 638 HNC patients were identified including 327 in the Pre‐Pandemic Cohort and 311 in the Pandemic Cohort. Patients in the Pandemic cohort had more N2‐N3 category (41% vs. 33%, p = 0.03), T3‐T4 category (63% vs. 50%, p = 0.002), and stage III‐IV (71% vs. 58%, p < 0.001) disease. Several intervals in the diagnosis to treatment pathway were significantly longer in the pandemic cohort as compared to the Pre‐Pandemic cohort. Among the pandemic cohort, 146 (47%) experienced a delay, with 112 related to the COVID‐19 pandemic; 80 (71%) were clinician related, 15 (13%) were patient related, and 17 (15%) were policy related. Conclusions: Patients in the Pandemic cohort had higher stage disease at diagnosis and longer intervals along the diagnostic pathway, with COVID‐19 related clinician factors being the most common cause of delay. [ABSTRACT FROM AUTHOR]

Measuring color matching differences between observers is an important means of investigating individual differences in human color vision. In this article, we introduce a new LED‐based visual trichromator with which we have estimated color matching functions and cone spectral sensitivities in a group of five normal observers. The trichromator has side‐by‐side semi‐circular matching fields that are illuminated by two spectrally tunable LED light sources, each comprised of 18 LEDs with center wavelengths ranging from 400 to 700 nm. We used Maxwell's method to derive a set color match. A fixed triplet of red‐green‐blue (RGB) primaries produced the white standard field of 120 cd/m2 in one field. The other field, the mixture field, was illuminated by one of 11 different triplets of lights with various center wavelengths. Observers adjusted the intensities of the triplets in the mixture field to match the white standard field. All matches were made for field diameters of 2° and 10° of visual angle to allow comparisons with colorimetric standards and were repeated five times. Calibrations and tests showed that the trichromator and the measurements were stable and repeatable. Grassmann's laws predict that at the 11 color matches the excitations in the three cone types should be the same. Consequently, we can use those matches and a model of how cone spectral sensitivities vary between individuals to estimate the three underlying corneal cone spectral sensitivities for each observer (and thus how they vary from the standard (or mean) observer). We find good agreement with the CIE 2006 standards, but our observers show small but consistent differences. [ABSTRACT FROM AUTHOR]

Objective: We evaluated vessel counts in the pharyngeal mucosal margins of patients who underwent salvage laryngectomy to establish whether mucosal vascularity might predict fistula risk. Study Design: Retrospective cohort. Setting: Tertiary Medical Center. Methods: Patients who underwent salvage total laryngectomy at our institution between 1999 and 2015 were identified. Pharyngeal mucosal margins from laryngectomy specimens were evaluated histologically for each patient, and vessel counts were performed on 5 ×10 images. The primary outcome measure was fistula within 30 days of surgery and mean vessel counts were assessed as the principle explanatory variable. Results: Seventy patients were included and 40% developed a postoperative fistula. There was a large difference in the mean vessel count in patients who did develop fistula (48.6 vessels/×10 field) compared to those who did not (34.7 vessels/×10 field). A receiver operative characteristic curve found that a cutoff value of 33.9 vessels/×10 field provided a sensitivity of 75% and specificity of 62% to predict the likelihood of fistula occurrence (area under the curve = 0.71, 95% confidence interval [CI]: 0.59‐0.83). In a binary logistic regression, patients with vessel counts greater than 33.9 had a 5‐fold increased risk of developing fistula (95% CI: 1.8‐16.45). Histologically, vessels in the pharyngeal mucosa of patients who developed fistulas were more disorganized. Conclusion: After salvage laryngectomy, patients with higher mean mucosal margin vessel counts are at increased risk of fistula. The mechanism is unknown, but the disorganization of the vasculature may contribute to poor wound healing. Vessel counting may allow for fistula risk stratification and guide postoperative care. [ABSTRACT FROM AUTHOR]

Objective: Analyze the duration of symptom‐free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient‐related or disease factors. Study Design: Retrospective review. Setting: Tertiary center. Methods: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer‐Cotton grade, distance between the glottis and superior‐most aspect of scar, DGS; length of scar, DL). Results: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time‐shortening from the 1st to 12th recurrence (P <.0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P <.01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P =.207, P =.20, P =.43, P =.16). Conclusion: Symptom‐free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR. Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

There is limited quantitative evidence of the effects of socio‐economic shocks on biological resource use. Focusing on wild meat hunting, a substantial livelihood and food source in tropical regions, we evaluated the impacts of the shock from Nigeria's coronavirus disease (COVID‐19) lockdown on species exploitation around a global biodiversity hotspot. Using a 3‐year quantitative dataset collected during and after the lockdown (covering 1008 hunter‐months) and matching by time of year, we found that successful hunting trip rates were more frequent during the lockdown, with a corresponding increase in the monthly number, mass, and value of animals caught. Moreover, hunters consumed a larger proportion of wild meat and sold less during lockdown, compared to non‐lockdown periods. These results suggest that local communities relied on wild meat to supplement reduced food and income during the lockdown, buffering the COVID‐19's socio‐economic shock. Our findings also indicate that wild species may be especially vulnerable to increased hunting pressure during socio‐economic shocks. [ABSTRACT FROM AUTHOR]

Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results: Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise. Plain Language Summary: The American Headache Society led a large, international, multistakeholder process to identify headache research topics that should be prioritized during the next 10 years. With input from headache clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public, 25 research priorities within 8 categories were identified. These research priorities can help guide headache researchers when planning their studies and as benchmarks by which the headache field can measure its progress over time. [ABSTRACT FROM AUTHOR]

The Alaskan Layered Pollution and Chemical Analysis (ALPACA) field campaign included deployment of a suite of atmospheric measurements in January–February 2022 with the goal of better understanding atmospheric processes and pollution under cold and dark conditions in Fairbanks, Alaska. We report on measurements of particle composition, particle size, ice nucleating particle (INP) composition, and INP size during an ice fog period (29 January–3 February). During this period, coarse particulate matter (PM10) concentrations increased by 150% in association with a decrease in air temperature, a stronger temperature inversion, and relatively stagnant conditions. Results also show a 18%–78% decrease in INPs during the ice fog period, indicating that particles had activated into the ice fog via nucleation. Peroxide and heat treatments performed on INPs indicated that, on average, the largest contributions to the INP population were heat‐labile (potentially biological, 63%), organic (31%), then inorganic (likely dust, 6%). Measurements of levoglucosan and bulk and single‐particle composition corroborate the presence of dust and aerosols from combustion sources. Heat‐labile and organic INPs decreased during the peak period of the ice fog, indicating those were preferentially activated, while inorganic INPs increased, suggesting they remained as interstitial INPs. In general, INP concentrations were unexpectedly high in Fairbanks compared to other locations in the Arctic during winter. The fact that these INPs likely facilitated ice fog formation in Fairbanks has implications for other high latitude locations subject to the hazards associated with ice fog. Plain Language Summary: The Alaskan Layered Pollution and Chemical Analysis field campaign occurred January–February 2022 with the goal of better understanding the atmosphere and atmospheric pollution during the winter in Fairbanks, Alaska. We studied a rare subset of atmospheric particles called ice nucleating particles which facilitate the formation of ice fog by allowing water to freeze at temperatures above −38°C. During our study, there was an ice fog event that coincided with a pollution event. During this event, there was a significant increase in coarse particulate matter associated with a decrease in temperature and calm winds. Ice nucleating particle concentration in the air decreased during the ice fog event indicating that the INPs had activated into the ice fog and were not able to be captured. We determined that most INPs were heat‐labile (potentially biological), followed by organic. Very few INPs were inorganic. Inorganic INPs increased during the ice fog period while heat‐labile and organic INPs decreased indicating that they were being selectively activated into the fog. Overall, INP concentrations in Fairbanks were quite high compared to other Arctic locations and carries implications for ice fog formation in other high‐latitude locations. Key Points: Fairbanks had higher wintertime ice nucleating particle (INP) concentrations than other high‐latitude locationsINP concentrations in Fairbanks decreased during the ice fog period, indicating that INPs were activated into the fogINP composition in Fairbanks was dominated by heat‐labile INPs [ABSTRACT FROM AUTHOR]

Background: Two phase 3 trials, POETYK PSO‐1 and PSO‐2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. Objectives: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. Methods: Pooled safety data were evaluated from PSO‐1 and PSO‐2 in which patients with moderate‐to‐severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. Results: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure‐adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person‐years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib. Conclusions: Deucravacitinib was well‐tolerated with acceptable safety over 52 weeks in patients with psoriasis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alzheimer's disease (AD) pathology is defined by β‐amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 훼‐synuclein aggregates) are a common co‐pathology for which effective biomarkers are needed. METHODS: A validated α‐synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB‐pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk‐factors, genetics, and cognitive trajectories. RESULTS: SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala‐predominant (60%) LB‐pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aβ burden but lower CSF p‐tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early‐AD who were already AD biomarker positive. DISCUSSION: SAA is a sensitive, specific marker for LB‐pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α‐synuclein co‐pathology in understanding AD's nature and progression. Highlights: SAA shows 79% sensitivity, 97% specificity for LB‐pathology detection in AD.SAA positivity prevalence increases with disease stage and age.Higher Aβ burden, lower CSF p‐tau181 linked with higher SAA+ rates in dementia.SAA+ impacts cognitive impairment in early disease stages.Study underpins need for wider LB‐pathology screening in AD treatment. [ABSTRACT FROM AUTHOR]

Summary: In this study, we compared the fat‐saturated (FS) and non‐FS turbo spin echo (TSE) magnetic resonance imaging knee sequences reconstructed conventionally (conventional‐TSE) against a deep learning‐based reconstruction of accelerated TSE (DL‐TSE) scans. A total of 232 conventional‐TSE and DL‐TSE image pairs were acquired for comparison. For each consenting patient, one of the clinically acquired conventional‐TSE proton density‐weighted sequences in the sagittal or coronal planes (FS and non‐FS), or in the axial plane (non‐FS), was repeated using a research DL‐TSE sequence. The DL‐TSE reconstruction resulted in an image resolution that increased by at least 45% and scan times that were up to 52% faster compared to the conventional TSE. All images were acquired on a MAGNETOM Vida 3T scanner (Siemens Healthineers AG, Erlangen, Germany). The reporting radiologists, blinded to the acquisition time, were requested to qualitatively compare the DL‐TSE against the conventional‐TSE reconstructions. Despite having a faster acquisition time, the DL‐TSE was rated to depict smaller structures better for 139/232 (60%) cases, equivalent for 72/232 (31%) cases and worse for 21/232 (9%) cases compared to the conventional‐TSE. Overall, the radiologists preferred the DL‐TSE reconstruction in 124/232 (53%) cases and stated no preference, implying equivalence, for 65/232 (28%) cases. DL‐TSE reconstructions enabled faster acquisition times while enhancing spatial resolution and preserving the image contrast. From these results, the DL‐TSE provided added or comparable clinical value and utility in less time. DL‐TSE offers the opportunity to further reduce the overall examination time and improve patient comfort with no loss in diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the safety of sub‐urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations. Patients and Methods: The patients were chemotherapy and immunotherapy naïve (bacille Calmette‐Guérin allowed) with non‐metastatic muscle‐invasive bladder cancer or non‐muscle‐invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose‐escalation design with sub‐urothelial injection of durvalumab at three pre‐determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC. Results: A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune‐related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2‐macrophage (CD163) when comparing the 25–150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033). Conclusion: Sub‐urothelial injection of durvalumab is feasible and safe without immune‐related AEs and shows local immunological effects. [ABSTRACT FROM AUTHOR]

Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8–12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non‐invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre‐ and post‐NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk‐of‐bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta‐analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk‐of‐bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta‐analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = −0.12, 95% CI = −0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF. [ABSTRACT FROM AUTHOR]

Summary: An 8‐year‐old Warmblood cross mare was presented for further investigation of an acute‐onset lameness of the right hindlimb. Three weeks prior to presentation, the horse was found markedly lame at walk following a fall during exercise. The horse was initially managed with field rest, but the lameness persisted. A marked right hindlimb lameness at trot graded 5/10 was confirmed. Atrophy of the right gluteal musculature was evident, and palpation over the region of the right coxofemoral joint provoked a pain reaction. Nuclear scintigraphy revealed a diffuse area of increased radiopharmaceutical uptake in the right femoral head, neck and greater trochanter. Radiographs identified a complete, slightly displaced fracture of the base of the greater trochanter of the right femur. Ultrasound examination of the proximal femur demonstrated an irregularity of the caudolateral bone surface of the greater trochanter, extending along its attachment to the femur; this was consistent with the radiological findings. On re‐examination, after 9 months of stable rest, the horse was found to be sound when trotted in a straight line on the hard surface. Follow‐up two and a half years after the initial incident reported the horse to be nonlame and at its previous level of work. [ABSTRACT FROM AUTHOR]