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Importance: Many social need screening to advance population health and reduce health disparities, but barriers to screening remain. Improved knowledge of patient populations at risk for social needs based on administrative data could facilitate more targeted practices, and by extension, feasible social need screening and referral efforts. Objective: To illustrate the use of cluster analysis to identify patient population segments at risk for social needs. Design: We used clustering analysis to identify population segments among Veterans (N=2010) who participated in a survey assessing nine social needs (food, housing, utility, financial, employment, social disconnection, legal, transportation, and neighborhood safety). Clusters were based on eight variables (age, race, gender, comorbidity, region, no-show rate, rurality, and VA priority group). We used weighted logistic regression to assess association of clusters with the risk of experiencing social needs. Participants: National random sample of Veterans with and at risk for cardiovascular disease who responded to a mail survey (N=2010). Main Outcomes and Measures: Self-reported social needs defined as the risk of endorsing (1) each individual social need, (2) one or more needs, and (3) a higher total count of needs. Key Results: From the clustering analysis process with sensitivity analysis, we identified a consistent population segment of Veterans. From regression modeling, we found that this cluster, with lower average age and higher proportions of women and racial minorities, was at higher risk of experiencing ≥ 1 unmet need (OR 1.74, CI 1.17–2.56). This cluster was also at a higher risk for several individual needs, especially utility needs (OR 3.78, CI 2.11–6.78). Conclusions: The identification of characteristics associated with increased unmet social needs may provide opportunities for targeted screenings. As this cluster was also younger and had fewer comorbidities, they may be less likely to be identified as experiencing need through interactions with healthcare providers. [ABSTRACT FROM AUTHOR]

Background: Migrants face barriers accessing healthcare, risking delays in cancer diagnosis. Diagnostic delays result in later stage diagnosis which is associated with poorer cancer survival. This review aims to compare the differences in cancer stage at diagnosis between migrants and non-migrants. Methods: We conducted a systematic review and meta-analysis of three databases from 2000 to 2023 for studies conducted in OECD countries that compared stage at diagnosis between migrants and non-migrants. Meta-analysis compared odds ratios (OR) for early (stage I and II) stage at diagnosis. The Risk of Bias in Non-randomised Studies of Exposure tool was used to assess study quality. Results: 41 of the 11,549 studies identified were included; 34 studies had suitable data for meta-analysis. Overall, migrants were significantly less likely to be diagnosed with early stage cancer compared with non-migrants (OR 0.84; 95% CI 0.78–0.91). This difference was maintained across cancer types, although only statistically significant for breast (OR 0.78; 95% CI 0.70–0.87) and prostate cancer (OR 0.92; 95% CI 0.85–0.99). Discussion: Published studies indicate that migrants are less likely to be diagnosed with early stage cancer. Variation by cancer type, study location and region of origin highlights the need for further research to understand these differences. [ABSTRACT FROM AUTHOR]

The skin, the body's largest organ, has a heterogeneous structure with various cell types and tissue layers. In vivo noninvasive 3D volumetric imaging with multi-contrast, high resolution, a large field-of-view (FOV), and no-motion artifacts is crucial for studying skin biology and diagnosing/evaluating diseases. Traditionally high-resolution in vivo skin microscopy methods capture images in the en-face (xy) plane parallel to the skin surface but are affected by involuntary motion, particularly during large-area volumetric data acquisition using xy-z mosaicking. In this work, we developed an xz-y imaging method that acquires images in the vertical (xz) plane and extends the FOV by moving the skin laterally along the y-direction. This approach is conceived based on our observation that involuntary skin movements are mostly along the vertical direction. Combined with a unique motion correction method, it enables 3D image reconstruction with subcellular resolution and an extended FOV close to a centimeter (8 mm). A multimodality microscopy system using this method provides simultaneous reflectance confocal, two-photon excited fluorescence, and second harmonic generation imaging, enabling multi-contrast capabilities. Using this system, we captured histology-like features of normal skin, vitiligo, and melanoma, demonstrating its potential for in vivo skin biology studies, clinical diagnosis, treatment planning and monitoring. A microscopy imaging method was developed for in vivo skin imaging by stacking vertical sectioning images to reconstruct 3D volume. It achieves multi-contrast, subcellular resolution, a near centimeter field of view, and is motion tolerant. [ABSTRACT FROM AUTHOR]

Significant changes have occurred during the last few decades across the North Atlantic climate system, including in the atmosphere, ocean, and cryosphere. These large-scale changes play a vital role in shaping regional climate and extreme weather events across the UK and Western Europe. This review synthesizes the characteristics of observed large-scale changes in North Atlantic atmospheric and oceanic circulations during past decades, identifies the drivers and physical processes responsible for these changes, outlines projected changes due to anthropogenic warming, and discusses the predictability of these circulations. On multi-decadal time scales, internal variability, anthropogenic forcings (especially greenhouse gases), and natural forcings (such as solar variability and volcanic eruptions) are identified as key contributors to large-scale variability in North Atlantic atmospheric and oceanic circulations. However, there remain many uncertainties regarding the detailed characteristics of these various influences, and in some cases their relative importance. We therefore conclude that a better understanding of these drivers, and more accurate quantification of their relative roles, are crucial for more reliable decadal predictions and projections of regional climate for the North Atlantic and Europe. [ABSTRACT FROM AUTHOR]

The goal of this study was to identify which anatomical and dosimetric changes correlated with late patient-reported dysphagia throughout the course of head and neck chemo-radiotherapy treatment. The patient cohort (n = 64) considered oropharyngeal and nasopharyngeal patients treated with curative intent, exhibiting no baseline dysphagia with a follow-up time greater than one year. Patients completed the MD Anderson Dysphagia Inventory during a follow-up visit. A composite score was measured ranging from 20 to 100, with a low score indicating a high symptom burden; a score ≤60 indicated patient-reported dysphagia. The pharyngeal (PCM) and cricopharyngeal constrictor muscles (CPM) were contoured on a planning CT image and adapted to weekly cone-beam CT anatomy using deformable image registration and dose was accumulated using weighted dose-volume histogram curves. The PCM and CPM were examined for volume, thickness, and dosimetric changes across treatment with the results correlated to symptom group. Anatomical evaluation indicated the PCM thickness increased more during treatment for patients with dysphagia, with base of C2 vertebrae (p = 0.04) and superior-inferior middle PCM (p = 0.01) thicknesses indicating a 1.0–1.5 mm increase. The planned and delivered mean dose and DVH metrics to PCM and CPM were found to be within random error measured for the dose accumulation, indicating delivered and planned dose are equivalent. The PCM and CPM organs were found to lie approximately 5 mm closer to high dose gradients in patients exhibiting dysphagia. The volume, thickness, and high dose gradient metrics may be useful metrics to identify patients at risk of late patient-reported dysphagia. [ABSTRACT FROM AUTHOR]

The basal forebrain (BF), in particular its cholinergic projections to cortex, has been implicated in regulation of attention in sensory systems. Here, we examine the role of GABAergic projections of the posterior nucleus basalis (pNB) and globus pallidus (GP) in attentional regulation in the auditory system. We employed a detection task where rats detected a narrow band target embedded in broad band noise, while optogenetically modulating GABAergic BF activity. We found that GABAergic BF modulation impacted target detection specifically close to perceptual threshold, consistent with a role in attentional modulation. We also present evidence for target frequency specificity of this modulation, including frequency selectivity and tonotopic organization of pNB/GP, as well as frequency band specific effects of optogenetics on behavioural target detection and on neural activity in auditory cortex and thalamus. Our findings highlight an important role of BF GABAergic neurons in modulating attention in the auditory pathway. We provide evidence for tonotopy in auditory basal forebrain and document that optogenetic modulation of efferent projections impact neural activity in thalamic and cortical auditory pathway structures, as well as influencing performance in an auditory detection task. [ABSTRACT FROM AUTHOR]

Piezoelectric materials directly convert between electrical and mechanical energies. They are used as transducers in applications such as nano-positioning and ultrasound imaging. Improving the properties of these devices requires piezoelectric materials capable of delivering a large longitudinal strain on the application of an electric field. A large longitudinal strain of more than 1% is generally anticipated in suitably oriented single crystals of specific compositions of ferroelectric materials1. Polycrystalline piezoceramics typically show a longitudinal strain of approximately 0.2–0.4%. We demonstrate that when the thickness of a polycrystalline piezoceramic is reduced to such an extent that a large fraction of the grains are in the triaxial–biaxal crossover regime, the domain-switching fraction increases considerably. If the positive and the negative surfaces of the piezoceramic respond to electric fields symmetrically, as in the classical PbZrxTixO3, a longitudinal strain of approximately 1% can be achieved in a 0.2 mm disc of the morphotropic phase boundary composition (a 300% increase from a thickness of 0.7 mm). We show that oxygen vacancies in piezoceramics cause asymmetrical switching at the positive and negative surfaces, which causes thin piezoceramics to bend. We expect these findings will encourage further engineering of these mechanisms across different piezoelectric material systems, opening new applications for electromechanical actuation.We find that if the thickness of a polycrystalline piezoceramic is reduced such that a large fraction of the grains are in the triaxial–biaxal crossover regime, the longitudinal strain is enhanced and the piezoceramic bends. [ABSTRACT FROM AUTHOR]

Copulation is essential for transferring sperm from males to females in most animals. During copulation, males and females are often static and thus prone to predation or other threats. Its duration should therefore be reduced to minimize costs but sufficient to ensure the fertilization of eggs. Here, we investigated reproductive behavior and success in the false widow spider, Steatoda grossa (Araneae: Theridiidae), when copulation was interrupted after 1, 3, 5, 10, or 20 min or was not experimentally interrupted (control). Copulation duration in this study is defined as the total duration of insertions of male pedipalps into a female's copulatory openings. In S. grossa, uninterrupted copulations typically last 40 to 60 min. We found that within the first 5 min, copulation interruption negatively affected reproductive success (i.e., number of egg sacs, their total mass, and number of spiderlings), and delayed production of the first egg sac within the first 10 min (in some extreme instances by over 200 days). However, when copulation duration was 10 min or longer, reproductive outcome was unaffected. In the 1-min treatment, the number of egg sacs and their mass varied greatly, which indicates considerable variation among males with respect to the speed and efficiency of sperm transfer. We discuss the costs and benefits of extended copulation duration on female reproduction and on male and female fitness. Significance statement: Interrupted copulation had a significant negative effect on reproductive success in the false widow spider, Steatoda grossa, but only if mating was terminated within the first 10 min of copulation. This implies that early during the copulation sequence sufficient amounts of sperm are transferred to fertilize most of the female's eggs. When copulation duration is less than 10 min, female spiders delayed the time to first reproduction. Prolonging the latency of reproduction can significantly affect female fitness. The role of extended mating in arthropods has focused on its effects on mate guarding, male-male competition for access to females and decreasing a female's attractiveness to other males. Preliminary data suggest that extended copulation does not reduce receptivity of S. grossa females to other males. Prolonged mating in S. grossa may play a more important role in reproductive success of the males. [ABSTRACT FROM AUTHOR]

Generalist predator populations often surge during resource pulses but decline sharply afterwards and shift to alternative prey sources, which experience elevated predation rates. Understanding these numerical and functional responses of predators to resource pulses is especially important for effectively managing island ecosystems, where invasive mammals are generalist predators and vulnerable indigenous birds are alternative prey. We used DNA metabarcoding of stomach contents to test whether the proportion of black rats (Rattus rattus) consuming birds changed during and after a mast seeding year in a New Zealand beech forest. Contrary to prevailing assumptions that black rats in forests consume birds only occasionally and increase their consumption of birds once a resource pulse finishes, we found that the overall proportion of rats consuming birds was surprisingly high (19.4%), and that the proportion of rats consuming birds did not change significantly across the three years of a beech mast cycle. We detected 15 unique bird taxa in the rat stomachs and 40 unique plant taxa. The frequency of beech consumption declined across the three years, as predicted. We conclude that (1) forest birds are a common part of rat diet rather than an occasional opportunistic prey item, and (2) the impact of black rats on indigenous birds following seed pulses is predominantly driven by the numerical response (increased numbers of rats present) rather than a functional (prey switching) response. Conservation interventions that seek to maximally and consistently suppress rats are therefore likely to have the best outcomes for birds. [ABSTRACT FROM AUTHOR]

Previous studies suggest social support is associated with musculoskeletal health in later life. We explored this relationship further in community-dwelling older adults, by considering associations between different aspects of social support and musculoskeletal health in community-dwelling adults. Participants from the Hertfordshire Cohort Study reported level of confiding/emotional, practical, and negative support using the Close Persons Questionnaire. Muscle strength was measured by grip strength dynamometry, and physical capability by timed up-and-go, chair rises, and walking speed tests. Bone mineral density (BMD) was assessed using dual-energy x-ray absorptiometry. Linear regression, adjusted for age, sex, body mass index (BMI), alcohol, smoking, physical activity, social class, and diet, was used for analysis. 1842 men and women (mean age 65.7 years) participated. Low emotional support correlated with weaker grip strength and poorer physical capability tests, although estimates were not robust to adjustment for confounders. Low practical support was linked to shorter timed up-and-go (β − 0.171, 95%CI − 0.319, − 0.024) and walking speed times (β − 0.157, 95%CI − 0.306, − 0.007), following adjustment for confounders. Negative support (i.e. the perceived inadequacy of the support received) was associated with lower grip strength (β − 0.145, 95%CI − 0.223, − 0.067) and slower walking speeds (β 0.159, 95%CI 0.004, 0.314). No social support exposures were associated with BMD. Different types of social support are linked to various measures of musculoskeletal health in older adults. Limited requirement for practical support correlated with better physical capability, while negative support correlated with poorer outcomes. No social support measure was associated with BMD. [ABSTRACT FROM AUTHOR]

The wildfire outbreak that occurred in Oklahoma on March 31, 2023, impacted structures and transportation infrastructure, posed significant challenges to emergency response, and tested the community's resilience. Extensive structural damage, including the destruction of numerous homes and electrical power poles, shows the need for improved wildfire mitigation strategies. The significant impact of the resulting smoke from the wildfire outbreak was highlighted by road closures, which disrupted transportation and school operations. Crucial firefighting operations, led by multiple fire departments and assisted by federal agencies, played a pivotal role in containing the fires. Additionally, community resilience was evident through evacuations and sheltering efforts, with churches and organizations providing refuge. Further, widespread electrical outages, caused by damaged infrastructure due to high winds, presented additional challenges. This study examines the multifaceted effects of the wildfire outbreak by recounting and analyzing the sequence of events. Further, a meteorological and wildfire hazard assessment, using historical data, was performed to provide insights for risk mitigation. Wildfire hazard maps for the state of Oklahoma were utilized to enhance emergency response and mitigation strategies for wildfires. An examination of wildfire risk perceptions among Oklahomans, both before and after the wildfire outbreak, reveal that the degree of personal connection to or remoteness from the wildfire event has a significant impact on how they perceive the wildfire risk. This study presents lessons and recommendations to enhance wildfire resilience. The findings contribute to a better understanding of the multifaceted impact of wildfire outbreaks to enhance community resilience and disaster response to wildfires. [ABSTRACT FROM AUTHOR]

Summary: This study aims to understand how osteoporosis medication acceptance varies across countries with differing guidance on treatment threshold and influence of clinical and demographic factors. A total of 79.2% accepted treatment at a fracture probability at or below the treatment threshold. Fracture history and age did not strongly impact acceptance, suggesting a need for improved fracture risk communication. Purpose: This part of the Improving Risk Communication in Osteoporosis (RICO) study aims to understand patients' willingness to initiate osteoporosis treatment given a hypothetical fracture probability—derived from the FRAX® Risk Assessment Tool—and how age, fracture history, and numeric literacy may influence this. Methods: In 2022–2023, 332 postmenopausal women at risk of fracture were interviewed from nine countries to determine participants' Fracture Risk Decision Point (FRDP), the lowest probability of major osteoporotic fracture at which they would accept an osteoporosis medication. Participants' FRDP was evaluated given eight hypothetical 10-year FRAX scores. Results: In countries with FRAX-based treatment thresholds, over half of the participants per country reported an FRDP that was below the threshold. Collectively, 79.2% demonstrated FRDPs at or below their respective threshold. Age and fracture history did not have a strong influence on FRDP; however, those who demonstrated higher levels of numeric literacy reported a significantly higher median FRDP (10%) compared to those who showed lower levels (5%, p < 0.001). Conclusions: Most patients were willing to accept an osteoporosis medication prescription at a hypothetical FRAX probability that was even lower than that of their nationally recommended treatment threshold. Literacy scores had a significant influence on FRDP whereas age and fracture history did not. [ABSTRACT FROM AUTHOR]

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment. [ABSTRACT FROM AUTHOR]

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells. Here, we present the safety, pharmacokinetics and pharmacodynamics of belinostat and pevonedistat in a dose escalation Phase I study in AML and High-Risk MDS. Methods: Eighteen patients (16 with AML, 2 with MDS) were treated at 5 dose levels (belinostat 800–1000 mg/m2, pevonedistat 20–50 mg/m2). Safety and tolerability were assessed according to protocol defined dose limiting toxicities (DLTs). Correlative pharmacokinetic and pharmacodynamic analyses were performed. Results: No dose limiting toxicities were noted. Most Grade 3 or 4 toxicities were hematologic in nature. The best response was stable disease in four patients, and complete remission in one patient who qualified as an exceptional responder. Pharmakokinetic studies revealed no association between drug exposure and best response. Pharmacodynamic RT-PCR studies demonstrated post-treatment increases in several proteins, including quantitative increases in the oxidative stress protein NQO1, ferroptosis protein SLC7A11, and GSR, linked to glutathione metabolism and oxidative stress, as did the anti-oxidants SRXN1 and TXNRD1. Conclusions: Patterns of post-treatment changes in correlative pharmacodynamic parameters may suggest possible mechanistic changes in the DNA damage response, oxidative damage, and ferroptosis pathways. The combination of pevonedistat plus belinosat is safe in an adult relapsed and/or refractory AML/High-Risk MDS population with modest but notable activity in this heavily treated, high risk population. Our findings also raise the possibility that certain extremely poor prognosis AML patients may respond to a regimen combining two targeted agents that have little or no activity when administered individually. Trial registration: ClinicalTrials.gov ID NCT03772925, first posted 12/12/2018; CTEP Identifier 10246. [ABSTRACT FROM AUTHOR]

The focus of this pilot investigation was to determine if the EA Briefing (previously referred to as the EA Brief), could improve self-reported and observed emotional availability (EA) as well as maternal wellbeing. Participants in this study were mothers and their children, including infants, preschoolers, school-aged children, and adolescents. All assessments were administered prior to and at the end of the intervention. These assessments included the observational Emotional Availability (EA) Scales, the Emotional Availability Self-Report (EA-SR), and the Flourishing Scale. During the intervention, mother-child dyads were in their homes and filmed via Zoom. Each mother completed a single, short, individualized parent feedback and coaching session and received information about emotional availability, attachment, and mindfulness. Results examined differences between the groups and indicated that those who received the intervention showed more improvement in observed EA and self-reported EA than those who did not. Additionally, parent-child dyads of all age groups in the study demonstrated improvements. This suggests that the EA Briefing may be relevant for a wider age range of children than have previously participated. The study may also encourage other attachment-based interventions to examine their effectiveness with older children. Highlights: This paper explores the implementation of the EA Briefing, an evidence-based intervention that provides feedback and coaching about EA to parents with the children in the study being between 0 and 17 years of age. The EA Briefing involves a 2-h group workshop on EA, attachment, and mindfulness, 1 h of individualized, video-based EA feedback, and uni-directional group texts to reinforce these concepts. Findings suggest that parent-child relationships from infancy through adolescence may be improved through this brief intervention model. [ABSTRACT FROM AUTHOR]

Purpose: To identify, critically appraise, and synthesise the published and grey literature on person-centred crisis support services as an alternative to support in emergency departments (EDs) for people experiencing mental health crises. This scoping review explores the characteristics and outcomes of these services. Methods: A systematic scoping review was undertaken to identify publications describing person-centred crisis support services and their outcomes. Search strings were applied to multiple databases, and publications were subjected to quality appraisal. The review process was informed by The Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). Results: Thirteen publications were included in the narrative synthesis, and these considered eight separate crisis support services. The methodological quality of the publications included was limited. Key findings were positive visitors' experiences, high rates of ED deflection, and overlaps between repeat visits, crises prevention, and hospital avoidance. Key recommendations included increasing opening hours and capacity and improving service awareness and accessibility. Conclusions: The available evidence suggests that person-centred crisis support services are perceived by stakeholders as safe and effective alternatives to EDs for people experiencing mental health crises, providing more timely and appropriate care while reducing ED mental health presentations. Due to the limited quality of the publications included, high-quality research is needed to better understand the model and confirm the findings reported in this review. [ABSTRACT FROM AUTHOR]

Purpose: Limited data exists on the relationship between sociodemographic and cultural variables and the prevalence of specific mental and substance use disorders (MSDs) among Indigenous Australians, using diagnostic prevalence data. This paper utilises data from the Queensland Urban Indigenous Mental Health Survey (QUIMHS), a population-level diagnostic mental health survey, to identify socioeconomic and cultural correlates of psychological distress and specific MSDs in an urban Indigenous Australian sample. Methods: Using a mixture of household sampling (door-knocking) and snowball sampling (promotion of the survey in the community), 406 participants aged 18 to 89 were recruited across key locations in Southeast Queensland. The study investigated various demographic, socioeconomic, and cultural factors as predictors of psychological distress (measured by the Kessler-5) and MSD diagnoses (utilising the Composite International Diagnostic Interview, CIDI 3.0) using a series of univariate logistic regressions. Results: Individuals in unstable housing (homeless, sleeping rough) and those reporting financial distress were more likely to experience an MSD in the past 12 months and throughout their lifetime. Individuals reporting lower levels of connection and belonging, limited participation in cultural events, and lower empowerment were more likely to have a lifetime mental disorder. Conclusion: This data emphasises the importance of addressing systemic and social determinants of health when designing and delivering community mental health services and underscores the need for holistic approaches when working with Indigenous communities. [ABSTRACT FROM AUTHOR]

We describe a testbed to characterize the optical response of compact superconducting on-chip spectrometers in development for the EXperiment for Cryogenic Large-Aperture Intensity Mapping (EXCLAIM) mission. EXCLAIM is a balloon-borne far-infrared experiment to probe the CO and CII emission lines in galaxies from redshift 3.5 to the present. The spectrometer, called µ-Spec, comprises a diffraction grating on a silicon chip coupled to kinetic inductance detectors (KIDs) read out via a single microwave feedline. We use a prototype spectrometer for EXCLAIM to demonstrate our ability to characterize the spectrometer's spectral response using a photomixer source. We utilize an on-chip reference detector to remove the spectral structure introduced by the off-chip optics and a silicon etalon to calibrate the absolute frequency. [ABSTRACT FROM AUTHOR]

Purpose of Review: We aim to describe the immunoassays that have been used for myositis autoantibody discovery with a focus on newer methods. We describe recently identified myositis autoantibodies that do not yet form part of routine clinical testing, highlighting what is known about their associated clinical phenotype and potential clues as to their presence. Recent Findings: Novel approaches to autoantibody detection have been employed in recent years including chemiluminescent immunoassay, phage immunoprecipitation-sequencing and modifications to the more traditional immunoprecipitation technique. This has led to the discovery of novel autoantibodies, including novel anti-aminoacyl-tRNA synthetase autoantibodies and autoantibodies which modify cancer risk for patients with anti-TIF1ɣ associated dermatomyositis. Summary: New approaches to novel autoantibody detection have facilitated autoantibody discovery and will enable the identification of autoantibodies to a broader range of autoantigens. Challenges remain in translating this knowledge into accessible testing particularly given the rarity of most recently discovered autoantibodies. [ABSTRACT FROM AUTHOR]

Pterygium is an ocular disease in which the conjunctival tissue invades the cornea. When the pterygium tissue reaches the pupillary region, the visual function of the patient is affected. Currently, surgical removal is the only effective treatment. However, the recurrence rate of pterygium after surgery can be high. Pterygium is also a health disparity issue since it is more prevalent in the Hispanic and Latino American population. In this study, we determined if the Rho kinase inhibitor can be used to prevent pterygium recurrence since its anti-fibrosis effects have been reported in other cell and tissue types. We cultured primary pterygium cells from pterygium tissues from Hispanic and Latino American, African American, Caucasian, and Asian donors, and used those cells for viability assays, scratch assays, migration assays, and immunostaining of F-actin, fibronectin, collagen I and α smooth muscle actin. We found that the Rho kinase inhibitor Y27632 decreased cell viability, wound healing, cell migration, as well as the expression of extracellular matrix and myofibroblast markers in cultured pterygium cells. We believe that Rho kinase inhibitors are a potential post-surgical treatment to prevent pterygium recurrence. [ABSTRACT FROM AUTHOR]

Over the last decade metagenomic sequencing has facilitated an increasing number of virome-scale studies, leading to an exponential expansion in understanding of virus diversity. This is partially driven by the decreasing costs of metagenomic sequencing, improvements in computational tools for revealing novel viruses, and an increased understanding of the key role that viruses play in human and animal health. A central concern associated with this remarkable increase in the number of virome-scale studies is the lack of broadly accepted "gold standards" for reporting the data and results generated. This is of particular importance for animal virome studies as there are a multitude of nuanced approaches for both data presentation and analysis, all of which impact the resulting outcomes. As such, the results of published studies can be difficult to contextualise and may be of reduced utility due to reporting deficiencies. Herein, we aim to address these reporting issues by outlining recommendations for the presentation of virome data, encouraging a transparent communication of findings that can be interpreted in evolutionary and ecological contexts. Virome-scale studies are changing our understanding of the virosphere, but deficiencies in reporting may limit the value of these studies. To increase the usefulness of virome-scale studies, 10 recommendations for the improvement of reporting are provided. [ABSTRACT FROM AUTHOR]

Multiferroic materials, which exhibit coupled ferroelectric and magnetic properties, hold immense promise for multifunctional device applications. Here, a multistep synthesis method, involving chemical synthesis, mechanical milling, and Spark Plasma Sintering, was utilized to fabricate (1-x)BaTiO3-xCoFe2O4 (BTO-CFO) compacted ceramics composites with x = 0.1, 0.2, 0.3, and 0.4. Controlled high pressure and pulsed current facilitated rapid densification, yielding high-density fine microstructures. Structural analysis confirmed the coexistence of tetragonal BaTiO3 (BTO) and cubic spinel CoFe2O4 (CFO) phases, forming 0–3 type multiferroic composites. Microstructural analysis revealed CFO grain clustering within the BTO matrix. The temperature-dependent magnetization curve of CFO shows an increase in magnetization within the temperature range of BTO ferroelectric phase transition, suggesting a strain-mediated magnetoelectric coupling. Temperature and frequency dependence of dielectric permittivity highlighted significant CFO conductivity contribution. Ferroelectric hysteresis and magnetoelectric coupling were observed predominantly in low CFO content samples, with differences in magnetoelectric coefficient values attributed to preferential ferroelectric polarization alignment. Our findings suggest that achieving high interface coupling is very challenging due to high leakage current from the magnetic phase. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) metabolism and cell growth uniquely rely on glutamine uptake by the transporter ASCT2. Despite previous data reporting cell growth inhibition after ASCT2 knockdown, we here show that ASCT2 CRISPR knockout is tolerated by TNBC cell lines. Despite the loss of a glutamine transporter and low rate of glutamine uptake, intracellular glutamine steady-state levels were increased in ASCT2 knockout compared to control cells. Proteomics analysis revealed upregulation of macropinocytosis, reduction in glutamine efflux and increased glutamine synthesis in ASCT2 knockout cells. Deletion of ASCT2 in the TNBC cell line HCC1806 induced a strong increase in macropinocytosis across five ASCT2 knockout clones, compared to a modest increase in ASCT2 knockdown. In contrast, ASCT2 knockout impaired cell proliferation in the non-macropinocytic HCC1569 breast cancer cells. These data identify macropinocytosis as a critical secondary glutamine acquisition pathway in TNBC and a novel resistance mechanism to strategies targeting glutamine uptake alone. Despite this adaptation, TNBC cells continue to rely on glutamine metabolism for their growth, providing a rationale for targeting of more downstream glutamine metabolism components. Synopsis: Glutamine uptake fuels triple-negative breast cancer (TNBC) sustaining anabolism and rapid growth, however the underlying mechanisms remain unclear. Here, TNBC cells are shown to tolerate loss of glutamine transporter expression and acquire resistance via inducible acquisition of extracellular carbon sources. Knockout of glutamine transporter ASCT2 leaves human TNBC cell growth unaffected. ASCT2 deletion induces macropinocytosis and utilisation of glucose carbons for glutamine production, restoring intracellular glutamine levels and cell growth. Macropinocytosis-acquired glutamine relies on free amino acids from the culture medium, and is independent of protein breakdown. Macropinocytosis induction is transient and can be rescued by ASCT2 re-expression. Glutamine addiction of malignant mammary epithelial cells relies on compensatory acquisition of extracellular carbon sources. [ABSTRACT FROM AUTHOR]

Sugarcane orange rust, caused by Puccinia kuehnii, was first described in Java/Indonesia at the end of the nineteenth century. The disease was confined to Asia and Oceania before appearing in the Western Hemisphere at the beginning of the twenty-first century. In the Western Hemisphere, orange rust was first observed in Florida in 2007 and subsequently also diagnosed in Africa (Cameroon and Côte d'Ivoire). Although symptoms of the disease were observed in Gabon as early as 2006, the formal molecular identification of the pathogen was never performed. In this study, leaf samples were collected in Gabon in 2022 from four sugarcane varieties displaying typical symptoms of orange rust. The microscopic characteristics of the foliar lesions (uredinia or pustules) and fungal spores taken from these lesions corresponded to the description of P. kuehnii in the literature. DNA was amplified from urediniospores by multiple displacement amplification and used in a PCR assay with primer pair Pk1F/R specific for P. kuehnii. All 12 tested spore samples (three per sugarcane variety) yielded the expected ~ 500 bp DNA fragment and forward sequenced amplicons matched with P. kuehnii in the GenBank database. DNA amplicons from two varieties (FR94129 and Q203) were cloned and sequenced in both directions. The 524–526 nucleotide sequences of eight clones matched at 99.6–100% with sequences of P. kuehnii in the GenBank database. This is the first report of occurrence of P. kuehnii in Gabon based on microscopy and molecular data. [ABSTRACT FROM AUTHOR]

Summary: Sequential romosozumab-to-alendronate or sequential teriparatide-to-alendronate can be a cost-effective treatment option for postmenopausal women at very high risk of fracture. Purpose: To estimate the 10-year probability of a major osteoporotic fracture (MOF) at which sequential treatment with romosozumab or teriparatide followed by alendronate, compared with alendronate alone, becomes cost-effective in a UK setting. Methods: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), in women receiving sequential treatment with either romosozumab or teriparatide followed by alendronate, compared with alendronate alone. Patients aged 50 to 90 years with a recent MOF, hip or spine fracture were followed from the start of a 5-year treatment until the age of 100 years or death. The analysis had a healthcare perspective. Efficacy of romosozumab, teriparatide and alendronate was derived from phase III randomised controlled trials. Resource use and unit costs were derived from the literature. Cost-effectiveness intervention threshold (CEIT), defined as the 10-year probability of a major osteoporotic fracture at which treatment becomes cost-effective, was compared with clinically appropriate intervention thresholds for bone-forming treatment in women with very high fracture risk as recommended by the UK National Osteoporosis Guideline Group (NOGG). Results: The base case analysis showed that sequential romosozumab-to-alendronate treatment was cost-effective from a 10-year MOF probability of 18–35% and above depending on age and site of sentinel fracture at a willingness to pay (WTP) of £30,000. For teriparatide-to-alendronate, treatment was cost-effective at a 10-year MOF probability of 27–57%. The results were sensitive to pricing of the drugs but relatively insensitive to treatment duration, romosozumab persistence assumptions, and site of sentinel fracture. The CEITs for romosozumab-to-alendronate treatment were lower than the clinical thresholds from the age of 70 years meaning that treatment could be considered both cost-effective and aligned with the NOGG treatment guidelines. By contrast, for teriparatide-to-alendronate the CEITs were higher than the clinical thresholds irrespective of age. However, cost-effective scenarios were found in the presence of strong clinical risk factors in addition to a recent sentinel fracture. Conclusion: The results of this study indicate that sequential romosozumab-to-alendronate or teriparatide-to-alendronate treatment can be a cost-effective treatment option for postmenopausal women at very high risk of fracture. [ABSTRACT FROM AUTHOR]

This study facilitates design of expression vectors and lentivirus tools for gene editing of Atlantic salmon. We have characterized widely used heterologous promoters and novel endogenous promoters in Atlantic salmon cells. We used qPCR to evaluate the activity of several U6 promoters for sgRNA expression, including human U6 (hU6), tilapia U6 (tU6), mouse U6 (mU6), zebrafish U6 (zU6), Atlantic salmon U6 (sU6), medaka U6 (medU6), and fugu U6 (fU6) promoters. We also evaluated several polymerase type II (pol II) promoters by luciferase assay. Our results showed that hU6 and tU6 promoters were the most active among all the tested U6 promoters, and heterologous promoters (CMV, hEF1α core) had higher activity compared to endogenous Atlantic salmon promoters sHSP8, sNUC3L, sEF1α. Among endogenous pol II promoters, sEF1α and sHSP8 displayed higher activity than sNUC3L, sHSP703, sHSP7C, sXRCC1L, and sETF. We observed that extending the promoter sequence to include the region up to the start codon (ATG) resulted in a significant increase in expression efficiency for sNUC3L and sEF1α. We also show that mutating the PRDM1 motif will significantly decrease the activity of the sEF1α promoter. The presence of the PRDM1 motif in sHSP8 promoter was also associated with relatively high expression compared to the promoters that naturally lacked this motif, such as sNUC3L. We speculate that this short sequence might be included in other promoters to further enhance the promoter activity, but further experiments are needed to confirm this. Our findings provide valuable insights into the activity of different promoters in Atlantic salmon cells and can be used to facilitate further transgenic studies and improve the efficiency of transgene expression in Atlantic salmon. [ABSTRACT FROM AUTHOR]

Tilde is a new in-house developed solution that the GNS Science's GeoNet program has recently developed to provide storage and access to low sample rate datasets used to monitor tsunami, landslides, and volcanoes in Aotearoa New Zealand. It includes datasets covering sample rates of 15 s or longer. Time series data are stored and disseminated in JSON and CSV formats, and users can access these through an application programming interface (API) and through graphical user interfaces (GUIs). Tilde's GUIs were created to allow technical and non-technical users easy access to the available data. The introduction of the Tilde system as one of the GeoNet program delivery channels has represented a big step forward for GeoNet's volcano data holdings by providing a single point to access all low to medium-sample rate volcano-specific monitoring data. We designed the system and developed a domain model, an API, a graphical data discovery interface, and associated data tutorials. This work leverages the open-by-default data policy for data generated through the GeoNet program. This paper is intended to highlight how we made many of the key decisions that shaped the Tilde system, how they were impacted by our multi-hazard monitoring requirements, and how they have improved access to volcano monitoring data. We conclude with some open questions about the need to develop common standards to share analysis-ready time series data within different disciplines in volcanology and geophysics. [ABSTRACT FROM AUTHOR]

I respond to the insightful comments of Liu Liangjian, Stephen Angle, and Trenton Wilson. [ABSTRACT FROM AUTHOR]

Long-term datasets provide context and understanding of complex ecological processes, including temporal variations in species diversity and ecosystem dynamics. This dataset is comprised of body length measurements (mm) of more than 380,000 larval or juvenile fish of 30 species from five English river catchments collected almost monthly over two decades. Such information can be used to determine growth rates, future recruitment success, population structure and compliance with monitoring protocols and conservation objectives. The dataset provides a baseline for analysing the impacts of anthropogenic disturbances such as climate change, pollution and habitat degradation, and, given that many fish populations are size structured with a positive relationship between fish body length and various biological attributes such as swimming ability, survival and fecundity, it will be invaluable for investigating natural and human- induced disturbances. [ABSTRACT FROM AUTHOR]

In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22–1.2 µm), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms. [ABSTRACT FROM AUTHOR]

Summary: A surrogate FRAX® model for Nepal has been constructed using age- and sex-specific hip fracture rates for Indians living in Singapore and age- and sex-specific mortality rates from Nepal. Introduction: FRAX models are frequently requested for countries with little or no data on the incidence of hip fractures. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country. Objective: This report describes the development and characteristics of a surrogate FRAX model for Nepal. Methods: The FRAX model used the ethnic-specific incidence of hip fracture in the Indian community of Singapore, combined with the death risk for Nepal in 2015–2019. The number of hip fractures in 2015 and 2050 was estimated based on the United Nations' predicted changes in population demography. Results: The surrogate model gave similar hip fracture probabilities to estimates from Sri Lanka, India and Pakistan but lower 10-year fracture probabilities for men and women at older ages compared to the model for Singapore, reflecting a higher mortality risk in Nepal compared with Singapore. There were very close correlations in fracture probabilities between the Nepalese and the Singapore models (r> 0.995) so that the use of the Nepalese model had little impact on the rank order of risk, i.e. a person at the xth percentile of risk with one model will be at the xth percentile of risk with the other. It was estimated that 6897 hip fractures arose in 2015 in individuals aged 50 years and older in Nepal, with a predicted 3-fold increase expected by 2050, when 23,409 hip fractures are expected nationally. Conclusion: The surrogate FRAX model for Nepal provides an opportunity to determine fracture probability within the Nepalese population and help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Purpose: Appendectomies are the most common abdominal emergency surgery in pediatric patients. Both pediatric and general surgeons are credentialed to perform this procedure, however pediatric surgeons are specialized in pediatrics. This study seeks to determine differences in pediatric appendectomy outcomes between general and pediatric surgeons. Methods: Pediatric patients undergoing appendectomies between 2015 and 2020 were identified in the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database. Multivariable logistic regression models examined association of surgeon specialty with readmission, postoperative complications, reoperation, non-home discharge destination, operative time, etc. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. Results: Average ages of pediatric patients undergoing appendectomy by pediatric and general surgeons were 11.2 (n = 68,638) and 12.3 (n = 3,986) years, respectively (p <.001). General surgeons were not more likely to have adverse outcomes [AOR: 1.00 (0.99–1.01), p = 0.57], readmissions [AOR: 0.995 (0.98–1.00), p = 0.11], reoperations [AOR: 1.00 (0.99–1.00), p = 0.54], or non-home discharges [AOR: 0.99 (0.99–1.00), p = 0.94]. Conclusions: Similar outcomes arise in pediatric appendectomies performed by general surgery at a children's hospital or hospitals with a pediatric wing. Significant limitations to using the NSQIP-P database persist. Further research including hospitals contributing to both adult and pediatric databases can provide a clearer picture of post-surgical outcomes in appendectomies. [ABSTRACT FROM AUTHOR]

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment. [ABSTRACT FROM AUTHOR]

Background and aims: The Richmond District of Queensland (Australia) hosts seleniferous soils and is the habitat of selenium (Se) hyperaccumulator plants. These soils are also naturally enriched in vanadium (V) and molybdenum (Mo). This study aimed to survey soils and plants of the Richmond area with a focus on the Se hyperaccumulator Neptunia amplexicaulis. Methods: Field collection of plant specimens and soils from the seleniferous outcrops of the Richmond District (including the Julia Creek area) was undertaken and the samples were analyzed for Se, V, Mo and other elements. Results: The results show that three modes of Se accumulation can be observed with most plant species having from ~10 μg Se g−1 up to 70 μg Se g−1 in shoots, some having between 75 and 250 μg Se g−1 in shoots while both N. amplexicaulis and Acacia tephrina contained 450–700 μg Se g−1 in their shoots. There was high Se accumulation in the phyllode tips of A. tephrina. Previously unrecorded populations of N. amplexicaulis were discovered near Julia Creek. Selenium concentrations in soil are lower than historically reported from similar localities (up to 23.2 mg Se kg−1). Molybdenum concentrations between 213 and 329 μg Mo g−1 occurred in the two Se hyperaccumulators N. amplexicaulis and A. tephrina, whilst Salsola australis had the highest accumulation of V (31–66 μg V g−1). Conclusions: The results suggest that the Toolebuc Formation is the source of Se in the region, but temporal variability alters how much Se is bioavailable to plants. The presence of high Mo in plant tissues is linked to Se hyperaccumulation, and V accumulation appears to have little impact on plant ecology. [ABSTRACT FROM AUTHOR]

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The global marine ecosystem is changing rapidly as the result of biogeochemical cycles and ecosystem structure being altered by industrial civilization. Invasive marine species (IMS) are one of the most damaging regional consequences of human activity, and one of the most easily attributable to specific processes. This makes IMS introduction one of most tractable threats for management by appropriate policies. Once established, a different set of policies are required either to restrict IMS spread, or to attempt local eradication. The key ecosystem management tool for IMS damage mitigation is rapid, widely deployable IMS detection. Environmental Nucleic Acids (eNA), combining environmental DNA (eDNA) and environmental RNA (eRNA) analyses, have emerged as valuable tools for sensitive, cost-effective and readily deployable detection of IMS. Methods for IMS detection by eNA are still being developed through a widespread and active research community, so identifying the limitations of current processes will help prioritise eNA-based IMS detection research. We analysed and synthesised the opinions of expert marine ecosystem managers and researchers in Australia and New Zealand about the knowledge gaps and research needs for eNA-based IMS detection. This synthesis was placed in context with current research literature on what eNA technologies are currently providing as an IMS management tool; what problems exist with the current technology; and what could be done to improve this general approach. Our analyses produced a list of priorities that chart a path towards the best possible systems for IMS detection by eNA. [ABSTRACT FROM AUTHOR]

Summary: Associations between different sarcopenia definitions and the risk of injurious falls were investigated in 75–80-year-old women in the Swedish SUPERB cohort. Only sarcopenia according to the Sarcopenia Definitions and Outcomes Consortium (SDOC) definition was associated with incident injurious falls with and without fractures in older women. Purpose: To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women. Methods: A total of 2,883 75–80-year-old women with complete data on relevant sarcopenia definitions from the Swedish SUPERB cohort were studied. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC: low handgrip strength and gait speed), revised European Working Group on Sarcopenia in Older People (EWGSOP2: low appendicular lean mass index (ALMI, dual-energy X-ray absorptiometry (DXA)-derived), appendicular lean mass (kg)/height (m2), hand grip strength (kg), or low chair stand time (s)), and Asian Working Group for Sarcopenia (AWGS: low ALMI and hand grip strength (kg) or low gait speed (m/s)). Questionnaires captured the occurrence of falls in the past 12 months. Incident injurious falls were identified using national registers. Cox regression (hazard ratios (HR) and 95% confidence intervals (CI)) analyses were performed without adjustment and after adjustment for age, body mass index, previous falls, and the Charlson comorbidity index. Results: During a median (IQR) follow-up time of 7.06 (6.2–7.9) years, there were 491 injurious falls without fracture and 962 injurious falls when also including falls resulting in a fracture. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased risk of injurious falls. Individuals with sarcopenia defined by SDOC had a higher risk of injurious falls with and without fracture (HR 2.11; 95% CI, 1.63–2.73 and HR, 2.16; 95% CI, 1.55–3.02, respectively). Conclusion: Sarcopenia definitions confined to muscle function and strength such as SDOC, rather than including DXA-determined ALMI (EWGSOP2 and AWGS), are associated with incident injurious falls with and without fractures in older women. [ABSTRACT FROM AUTHOR]

Microbiome-directed dietary interventions such as microbiota-directed fibers (MDFs) have a proven track record in eliciting responses in beneficial gut microbes and are increasingly being promoted as an effective strategy to improve animal production systems. Here we used initial metataxonomic data on fish gut microbiomes as well as a wealth of a priori mammalian microbiome knowledge on α-mannooligosaccharides (MOS) and β-mannan-derived MDFs to study effects of such feed supplements in Atlantic salmon (Salmo salar) and their impact on its gut microbiome composition and functionalities. Our multi-omic analysis revealed that the investigated MDFs (two α-mannans and an acetylated β-galactoglucomannan), at a dose of 0.2% in the diet, had negligible effects on both host gene expression, and gut microbiome structure and function under the studied conditions. While a subsequent trial using a higher (4%) dietary inclusion of β-mannan significantly shifted the gut microbiome composition, there were still no biologically relevant effects on salmon metabolism and physiology. Only a single Burkholderia-Caballeronia-Paraburkholderia (BCP) population demonstrated consistent and significant abundance shifts across both feeding trials, although with no evidence of β-mannan utilization capabilities or changes in gene transcripts for producing metabolites beneficial to the host. In light of these findings, we revisited our omics data to predict and outline previously unreported and potentially beneficial endogenous lactic acid bacteria that should be targeted with future, conceivably more suitable, MDF strategies for salmon. A multi-omic approach enables the reconstruction of microbial metabolic dynamics in the salmon gut in response to feed and feed supplements, outlining novel and potentially beneficial strategies to manipulate the salmon gut microbiota. [ABSTRACT FROM AUTHOR]

Clinical prediction models (CPMs) are tools that compute the risk of an outcome given a set of patient characteristics and are routinely used to inform patients, guide treatment decision-making, and resource allocation. Although much hope has been placed on CPMs to mitigate human biases, CPMs may potentially contribute to racial disparities in decision-making and resource allocation. While some policymakers, professional organizations, and scholars have called for eliminating race as a variable from CPMs, others raise concerns that excluding race may exacerbate healthcare disparities and this controversy remains unresolved. The Guidance for Unbiased predictive Information for healthcare Decision-making and Equity (GUIDE) provides expert guidelines for model developers and health system administrators on the transparent use of race in CPMs and mitigation of algorithmic bias across contexts developed through a 5-round, modified Delphi process from a diverse 14-person technical expert panel (TEP). Deliberations affirmed that race is a social construct and that the goals of prediction are distinct from those of causal inference, and emphasized: the importance of decisional context (e.g., shared decision-making versus healthcare rationing); the conflicting nature of different anti-discrimination principles (e.g., anticlassification versus antisubordination principles); and the importance of identifying and balancing trade-offs in achieving equity-related goals with race-aware versus race-unaware CPMs for conditions where racial identity is prognostically informative. The GUIDE, comprising 31 key items in the development and use of CPMs in healthcare, outlines foundational principles, distinguishes between bias and fairness, and offers guidance for examining subgroup invalidity and using race as a variable in CPMs. This GUIDE presents a living document that supports appraisal and reporting of bias in CPMs to support best practice in CPM development and use. [ABSTRACT FROM AUTHOR]

Formalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmarked the performance of the snPATHO-seq workflow against existing 10x 3' and Flex assays designed for frozen or fresh samples and highlighted the consistency in snRNA-seq data produced by all workflows. The snPATHO-seq workflow also demonstrated high robustness when tested across a wide range of healthy and diseased FFPE tissue samples. When combined with FFPE spatial transcriptomic technologies such as FFPE Visium, the snPATHO-seq provides a multi-modal sampling approach for FFPE samples, allowing more comprehensive transcriptomic characterization. A combination of an FFPE nuclei preparation protocol and a probe-based transcriptomic profiling technique enables snRNA-seq characterization of archival human FFPE tissues, holding promise for retrospective studies involving aged clinical cohorts. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical outcomes of canaloplasty performed with the iTrack microcatheter (Nova Eye Medical, Fremont, USA) as a standalone procedure and in combination with phacoemulsification in patients with primary angle-closure glaucoma (PACG). Methods: A single-center, retrospective case series of eyes undergoing canaloplasty via an ab-interno technique with a diagnosis of PACG based on gonioscopy findings (Shaffer grading). Patients were excluded if they had previously undergone a glaucoma procedure other than Laser Peripheral Iridotomy (LPI). Eyes were grouped by glaucoma severity based on mean deviation preoperative values. Outcome measures included intraocular pressure (IOP) and number of glaucoma medications. Results: Sixty eyes (9 canaloplasty-standalone, pseudophakic, and 51 canaloplasty + phaco) were eligible. The mean baseline IOP was 21.9 ± 7.3 mmHg and number of glaucoma medications was 1.95 ± 1.4. At the latest follow-up (mean 26 ± 9.2 months), they were reduced to 14.6 ± 3.7 mmHg (p < 0.001) and 0.96 ± 1.2 (p < 0.001). IOP reduction was statistically significant when canaloplasty was performed as a standalone procedure (baseline 22.78 ± 6.72 vs 17.00 ± 3.42 at the latest follow-up) or combined with phacoemulsification (21.75 ± 7.43 vs 14.21 ± 3.66) or if canaloplasty was performed in mild (20.8 ± 4.93 vs 15.5 ± 3.63), moderate (21.9 ± 8.58 vs 13.9 ± 3.90) or severe (23.5 ± 11.3 vs 12.4 ± 3.20) glaucoma eyes, with no difference between the groups postoperatively. Medication reduction was significant when canaloplasty was performed in combination with phacoemulsification and in mild glaucoma eyes. No serious intraoperative or postoperative complications were reported. Conclusion: Canaloplasty via an ab-interno surgical technique, performed as standalone or combined with phacoemulsification, is a safe and clinically effective treatment in primary angle closure glaucoma patients up to 2 years. [ABSTRACT FROM AUTHOR]

This retrospective case series (clinicaltrials.gov NCT06405282) used noninvasive imaging devices (NIID) to assess the effect of manual lymphatic drainage (MLD) on dermal/venous fluid distribution, perfusion, and temperature alterations of the head, neck, upper torso, and legs while in the 6-degree head-down tilt validated spaceflight analog. A lymphatic fluid scanner measured tissue dielectric constant levels. Near-infrared spectroscopy assessed perfusion, by measuring tissue oxygenation saturation. Long-wave infrared thermography measured tissue temperature gradients. Fifteen healthy, university students participated. NIID assessments were taken 1 minute after assuming the HDT position and then every 30 minutes, with MLD administered from 180 to 195 minutes. Subjects returned to the sitting position and were assessed at post-225 min NIID demonstrated significant changes from baseline (p < 0.01), although these changes at areas of interest varied. MLD had a reverse effect on all variables. NIID assessment supported the potential use of MLD to mitigate fluid shifts during a spaceflight analog. [ABSTRACT FROM AUTHOR]

Medical mistrust is an important barrier to accessing health care among Latinx populations in the United States (US). However, research on the validity and reliability of medical mistrust scales is limited. We examined the validity and reliability of a modified bilingual version of the Group-Based Medical Mistrust scale (mGBMMS) among a sample of Latinx adults. Participants included 308 Latinx adults (ages 18–25), who responded in Spanish (n = 134) or English (n = 174). Following feedback from bilingual/bicultural staff during the English-Spanish translation process, we made three changes to the original GBMMS. Validation testing of our 12-item mGBMMS scale included: split-half and internal consistency reliability; discriminant, convergent, and predictive validity; and both exploratory and confirmatory factor analyses. The mGBMMS had good internal consistency (overall sample: Cronbach's α = 0.79; Spanish: Cronbach's α = 0.73; English: Cronbach's α = 0.83). The mGBMMS showed good convergent (moderately correlated with the experiences of discrimination scale, r = 0.46, p < 0.001) and discriminant (weakly correlated with the acculturation scale, r = 0.11, p = 0.06) validity. Split-half reliability was 0.71 (p < 0.001). Exploratory and confirmatory factor analyses found a two-factor solution. The mGBMMS was associated with satisfaction with care (OR = 0.60, 95%CI: 0.42–0.87), a sign of good predictive validity. Findings suggest that the mGBMMS is a valid and reliable scale to utilize among bilingual (Spanish/English) populations in the US. Further validation studies should be considered among Latinx respondents of different ages, backgrounds, languages, and US regions. [ABSTRACT FROM AUTHOR]

An action is agentially perfect if and only if, if a person tries to perform it, they succeed, and, if a person performs it, they try to. We argue that trying itself is agentially perfect: if a person tries to try to do something, they try to do it; and, if a person tries to do something, they try to try to do it. We show how this claim sheds new light on questions about basic action, the logical structure of intentional action, and the notion of "options" in decision theory. On the way to these central ideas, we argue that a person can try to do something even if they believe it is impossible that they will succeed, that a person can try to do something even if they do not want to succeed, and that a person can try to do something even if they do not intend to succeed. [ABSTRACT FROM AUTHOR]

Purpose: Following laparoscopic anti-reflux surgery (LARS), recurrence of hiatal hernia is common. Patients with symptomatic recurrence typically undergo revision of the fundoplication or conversion to magnetic sphincter augmentation (MSA) in addition to cruroplasty. However, patients with an intact fundoplication or MSA may only require repeat cruroplasty to repair their recurrent hiatal hernia. The purpose of this study is to compare outcomes following cruroplasty alone compared to full revision (i.e. redo fundoplication or MSA with cruroplasty) for the management of recurrent hiatal hernias. Methods: A retrospective review of patients undergoing surgical revision of a symptomatic recurrent hiatal hernia between February 2009 and October 2022 was performed. Preoperative characteristics, intraoperative details, and postoperative outcomes were compared between patients undergoing cruroplasty alone versus full revision. Results: A total of 141 patients were included in the analysis. 93 patients underwent full revision, and 48 patients underwent cruroplasty alone. The mean time between initial and revisional surgery was 8 ± 7.7 years. There was no significant difference in operative time or rates of intra-operative or post-operative complication between groups. Patients undergoing cruroplasty alone had a mean Gastroesophageal Reflux Disease Health Related Quality Life (GERD-HRQL) Questionnaire score of 9.6 ± 10.2 compared to a mean score of 8.9 ± 11.2 for full revision patients (p = 0.829). Recurrence rates following revision was 10.4% for cruroplasty alone patients and 11.8% in full revision patients (p > 0.999). Conclusion: In patients with intact fundoplication or MSA, cruroplasty alone results in similar post-operative outcomes compared to full revision for recurrent hiatal hernia. [ABSTRACT FROM AUTHOR]