Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions Between HR‐pQCT Bone Density and D3Cr Muscle Mass (or HR‐pQCT Bone Structure and HR‐pQCT Muscle Density) in Predicting Fractures: The Osteoporotic Fractures in Men Study

We examined if an interaction exists between bone and muscle in predicting fractures in older men. Prospective data from the Osteoporotic Fractures in Men study was used to build Cox proportional hazards models. Predictors included HR‐pQCT total volumetric BMD (Tt.BMD), trabecular BMD (Tb.BMD), cortical BMD (Ct.BMD) and cortical area (Ct.Ar) at distal radius/tibia, HR‐pQCT muscle volume and density (diaphyseal tibia), D3‐creatine dilution (D3Cr) muscle mass, and grip strength and leg force, analyzed as continuous variables and as quartiles. Incident fractures were self‐reported every 4 months via questionnaires and centrally adjudicated by physician review of radiology reports. Potential confounders (demographics, comorbidities, lifestyle factors, etc.) were considered. A total of 1353 men (mean age 84.2 ± 4.0 years, 92.7% white) were followed for 6.03 ± 2.11 years. In the unadjusted (continuous) model, there were no interactions (p > 0.05) between any muscle variable (D3Cr muscle mass, muscle volume, muscle density, grip strength or leg force) and Tt.BMD at distal radius/tibia for fractures (all: n = 182–302; nonvertebral: n = 149–254; vertebral: n = 27–45). No consistent interactions were observed when interchanging Tt.BMD for Tb.BMD/Ct.BMD or for Ct.Ar (bone structure) at the distal radius/tibia in the unadjusted (continuous) models. Compared with men in quartiles (Q) 2–4 of D3Cr muscle mass and Q2–4 of distal tibia Tt.BMD, men in Q1 of both had increased risk for all fractures (hazard ratio (HR) = 2.00; 95% confidence interval [CI] 1.24–3.23, p = 0.005) and nonvertebral fractures (HR = 2.10; 95% CI 1.25–3.52, p < 0.001) in the multivariable‐adjusted model. Confidence intervals overlapped (p > 0.05) when visually inspecting other quartile groups in the multivariable‐adjusted model. In this prospective cohort study of older men, there was no consistent interactions between bone and muscle variables on fracture risk. Larger sample sizes and longer follow‐up may be needed to clarify if there is an interaction between bone and muscle on fracture risk in men. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Genitive variation: the niche role of the oblique genitive1

This article discusses the niche role that the oblique genitive of the type the friend of John’s occupies in the context of genitive variation. The article shows that the oblique genitive should be considered an independent construction which competes marginally in two syntactic contexts with the s-genitive (as in John's friend) and the of-genitive (as in the friend of John). The first context is one in which all three constructions function as the predicative complement of the clause (e.g. He is a friend of John's / John's friend / a friend of John). Note that in this context the definiteness effect of the s-genitive is downplayed, so that competition is possible with indefiniteness of the other two constructions. The second context is one where the oblique genitive and the of-genitive are introduced by the determiner the. Contrary to the claim that oblique genitive constructions introduced by the definite article must receive restrictive modification of the head (see e.g. Barker 1998; Lyons 1986), the quantitative data presented in this article reveal that oblique genitives introduced by the determiner the are not confined to pre- or postmodification of the head but can occur, albeit rarely, without any modification as in the example the executor of Sir Ralph’s. The article further compares the oblique genitive, s-genitive and of-genitive with respect to the following five features: noun-headed vs pronoun dependent; animacy of the dependent; length of the noun-headed dependent; determiner of the head; and the semantic relations that can hold between head (e.g. friend) and dependent (e.g. John). The most intriguing theoretical conclusion is that the semantic relations available to head and dependent in the oblique genitive are a subset of those found in the s-genitive, which, again constitute a subset of those that exist in the of-genitive. This means that variation between all three constructions is not only restricted to the two syntactic contexts outlined above but also to a shared set of semantic relations.
Transcriptomic effects of the foraging gene shed light on pathways of pleiotropy and plasticity

Genes are often pleiotropic and plastic in their expression, features which increase and diversify the functionality of the genome. The foraging (for) gene in Drosophila melanogaster is highly pleiotropic and a long‐standing model for studying individual differences in behavior and plasticity from ethological, evolutionary, and genetic perspectives. Its pleiotropy is known to be linked to its complex molecular structure; however, the downstream pathways and interactors remain mostly elusive. To uncover these pathways and interactors and gain a better understanding of how pleiotropy and plasticity are achieved at the molecular level, we explore the effects of different for alleles on gene expression at baseline and in response to 4 h of food deprivation, using RNA sequencing analysis in different Drosophila larval tissues. The results show tissue‐specific transcriptomic dynamics influenced by for allelic variation and food deprivation, as well as genotype by treatment interactions. Differentially expressed genes yielded pathways linked to previously described for phenotypes and several potentially novel phenotypes. Together, these findings provide putative genes and pathways through which for might regulate its varied phenotypes in a pleiotropic, plastic, and gene‐structure‐dependent manner.
A comparison of the CAPS-5 and PCL-5 to assess PTSD in military and veteran treatment-seeking samples

ABSTRACT Background: This study was an examination of the puzzling finding that people assessed for symptoms of posttraumatic stress disorder (PTSD) consistently score higher on the self-report PTSD Checklist for DSM-5 (PCL-5) than the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Both scales purportedly assess PTSD severity with the same number of items, scaling, and scoring range, but differences in scores between measures make outcomes difficult to decipher. Objective: The purpose of this study was to examine several possible psychometric reasons for the discrepancy in scores between interview and self-report. Method: Data were combined from four clinical trials to examine the baseline and posttreatment assessments of treatment-seeking active duty military personnel and veterans. Results: As in previous studies, total scores were higher on the PCL-5 compared to the CAPS-5 at baseline and posttreatment. At baseline, PCL-5 scores were higher on all 20 items, with small to large differences in effect size. At posttreatment, only three items were not significantly different. Distributions of item responses and wording of scale anchors and items were examined as possible explanations of the difference between measures. Participants were more likely to use the full range of responses on the PCL-5 compared to interviewers. Conclusions: Suggestions for improving the congruence between these two scales are discussed. Administration of interviews by trained assessors can be resource intensive, so it is important that those assessing PTSD severity are afforded confidence in the equivalence of their assessment of PTSD regardless of the assessment method used. HIGHLIGHTS The purpose of this study was to examine two commonly used measures of posttraumatic stress disorder, the Clinician-Administered PTSD Scale (CAPS-5), an interview measure, and the PTSD Checklist (PCL-5), a self-report measure, to explore discrepancies in scores. Both measures have the same number of items and range of scores assessing the identical 20 symptoms of PTSD, yet higher scores are reported on the PCL-5. It appears that the differences in wording of the anchors may contribute to discrepancies in scoring. Addressing these problems would allow for a better match in scoring between scales.
Community Health Worker Interventions for Men: A Scoping Review Using the RE-AIM Framework

Introduction Community health workers (CHWs) are health promotion specialists who are trusted members of the community served and have a close understanding of the community’s needs and values. CHWs are a cost-effective and scalable workforce to promote health among men through tailored approaches. The purpose of the present review was to use the RE-AIM Framework to assess design, implementation, and outcomes of CHW-implemented health promotion efforts tailored for men to provide recommendations for future efforts. Methods The protocol was pre-registered with PROSPERO. The primary inclusion criteria were that the interventions were (a) implemented at least partially by CHWs, (b) conducted only among men, and (c) designed to improve a health-related outcome. PubMed, EMBASE, PsycINFO, CINAHL, Web of Science, and Global Index Medicus were searched using a librarian-generated search strategy. In all, 1,437 articles were uploaded to Rayyan and two reviewers blindly reviewed each article for inclusion. A total of 24 articles met the inclusion criteria. Results Most interventions (a) targeted men under 50 years, (b) were conducted among a subset of underserved men, (c) improved health outcomes, (d) community-based and informed, (e) atheoretical, and (f) had satisfactory retention rates. The roles and responsibilities of CHWs were varied. Attention was given to training of CHWs, but limited attention was given to how/if the CHWs were supervised. Discussion CHW-implemented interventions can improve health outcomes among men. Opportunities exist to build on past interventions, such as addressing mental health and incorporating prosocial aspects of masculinity. The results have implications for designing similar interventions.
Association between migration and severe maternal outcomes in high-income countries: Systematic review and meta-analysis

Background Literature focusing on migration and maternal health inequalities is inconclusive, possibly because of the heterogeneous definitions and settings studied. We aimed to synthesize the literature comparing the risks of severe maternal outcomes in high-income countries between migrant and native-born women, overall and by host country and region of birth. Methods and findings Systematic literature review and meta-analysis using the Medline/PubMed, Embase, and Cochrane Library databases for the period from January 1, 1990 to April 18, 2023. We included observational studies comparing the risk of maternal mortality or all-cause or cause-specific severe maternal morbidity in high-income countries between migrant women, defined by birth outside the host country, and native-born women; used the Newcastle–Ottawa scale tool to assess risk of bias; and performed random-effects meta-analyses. Subgroup analyses were planned by host country and region of birth. The initial 2,290 unique references produced 35 studies published as 39 reports covering Europe, Australia, the United States of America, and Canada. In Europe, migrant women had a higher risk of maternal mortality than native-born women (pooled risk ratio [RR], 1.34; 95% confidence interval [CI], 1.14, 1.58; p < 0.001), but not in the USA or Australia. Some subgroups of migrant women, including those born in sub-Saharan Africa (pooled RR, 2.91; 95% CI, 2.03, 4.15; p < 0.001), Latin America and the Caribbean (pooled RR, 2.77; 95% CI, 1.43, 5.35; p = 0.002), and Asia (pooled RR, 1.57, 95% CI, 1.09, 2.26; p = 0.01) were at higher risk of maternal mortality than native-born women, but not those born in Europe or in the Middle East and North Africa. Although they were studied less often and with heterogeneous definitions of outcomes, patterns for all-cause severe maternal morbidity and maternal intensive care unit admission were similar. We were unable to take into account other social factors that might interact with migrant status to determine maternal health because many of these data were unavailable. Conclusions In this systematic review of the existing literature applying a single definition of “migrant” women, we found that the differential risk of severe maternal outcomes in migrant versus native-born women in high-income countries varied by host country and region of origin. These data highlight the need to further explore the mechanisms underlying these inequities. Trial Registration PROSPERO CRD42021224193.
Orographic influences on the mesoscale structure of the 1998 ice storm

Abstract The ice storm of 5–9 January 1998, affecting parts of the northeastern United States and the eastern Canadian provinces, was characterized by freezing rain amounts greater than 100 mm in some areas. The region of maximum precipitation occurred in a deformation zone between an anomalously cold surface anticyclone to the north and a surface trough axis extending from the Gulf of Mexico into the Great Lakes. Mesoscale processes were examined to understand their role in regulating the persistence, phase, and intensity of the event. The persistently cold near-surface air in the precipitating region was linked to orographic channeling of winds from the cold anticyclone to the north. The position of the surface-based freezing line was strongly tied to pressure-driven channeling of surface winds by orography during the first freezing rain episode (4–7 January), while this channeling contributed to the depth of the cold air north of the U.S. border and governed details of the position of the freezing line.
LOCATION OF THE ION-CYCLOTRON INSTABILITY REGION RELATIVELY TO PLASMAPAUSE DURING MAGNETOSPHERIC COMPRESSIONS

Compression of the magnetosphere by a jump of the solar wind dynamic pressure produces, among other consequences, a large-scale dayside precipitation of energetic protons responsible for sub-oval proton aurora flashes. These flashes are related to a sudden appearance of geomagnetic pulsations in the Pc1 range. Both proton precipitation (proton aurora) and Pc1 manifest the development of the ion-cyclotron instability in the equatorial plane of the magnetosphere. To explore the magnetospheric domain where the instability develops we combined the projection of the equatorial edge of the proton aurora flashes observed by the IMAGE spacecraft and plasmapause location. The latter was determined using the plasmapause model. It was shown that during magnetospheric compression an ion-cyclotron interaction mostly occurs outside plasmasphere. It was also found that the location of the Earthward edge of the ion-cyclotron instability region as well as the distance between this edge and plasmapause depends on preceding geomagnetic activity. During stronger geomagnetic activity the ion-cyclotron instability region tends to locate closer to the Earth and plasmapause.
Two-dimensional simulation of unsteady heat transfer from a circular cylinder in crossflow

The heat transfer from the surface of a circular cylinder into a crossflow has been computed using a two-dimensional model, for a range of Reynolds numbers from Re=200 to 15550. The boundary-layer separation, the local and overall heat-transfer rates, the eddy- and flare-detachment frequencies and the width of the flares were determined from the numerical simulations. In this range of Reynolds numbers, the heat-transfer process is unsteady and is characterized by a viscous length scale that is inversely proportional to the square root of the Reynolds number. To ensure uniform numerical accuracy for all Reynolds numbers, the dimensions of the computational mesh were selected in proportion to this viscous length scale. The small scales were resolved by at least three nodes within the boundary layers. The frequency of the heat flares increases, and the width of each flare decreases, with the Reynolds number, in proportion to the viscous time and length scales. Despite the presence of three-dimensional structures for the range of Reynolds numbers considered, the two-dimensional model captures the unsteady processes and produced results that were consistent with the available experimental data. It correctly simulated the overall, the front-stagnation and the back-to-total heat-transfer rates.
Non-linear properties of the Achilles tendon determine ankle impedance over a broad range of activations in humans

ABSTRACT Regulating ankle mechanics is essential for controlled interactions with the environment and rejecting unexpected disturbances. Ankle mechanics can be quantified by impedance, the dynamic relationship between an imposed displacement and the torque generated in response. Ankle impedance in the sagittal plane depends strongly on the triceps surae and Achilles tendon, but their relative contributions remain unknown. It is commonly assumed that ankle impedance is controlled by changing muscle activation and, thereby, muscle impedance, but this ignores that tendon impedance also changes with activation-induced loading. Thus, we sought to determine the relative contributions from the triceps surae and Achilles tendon during conditions relevant to postural control. We used a novel technique that combines B-mode ultrasound imaging with joint-level perturbations to quantify ankle, muscle and tendon impedance simultaneously across activation levels from 0% to 30% of maximum voluntary contraction. We found that muscle and tendon stiffness, the static component of impedance, increased with voluntary plantarflexion contractions, but that muscle stiffness exceeded tendon stiffness at very low loads (21±7 N). Above these loads, corresponding to 1.3% of maximal strength for an average participant in our study, ankle stiffness was determined predominately by Achilles tendon stiffness. At approximately 20% MVC for an average participant, ankle stiffness was 4 times more sensitive to changes in tendon stiffness than to changes in muscle stiffness. We provide the first empirical evidence demonstrating that the nervous system, through changes in muscle activations, leverages the non-linear properties of the Achilles tendon to increase ankle stiffness during postural conditions.
Role of Conserved Tyrosine Lid Residues in the Activation of the M2 Muscarinic Acetylcholine Receptor

The development of subtype selective small molecule drugs for the muscarinic acetylcholine receptor (mAChR) family has been challenging. The design of more selective ligands can be improved by understanding the structure and function of key amino acid residues that line ligand binding sites. Here we study the role of three conserved key tyrosine residues [Y1043.33, Y4036.51, and Y4267.39 (Ballesteros and Weinstein numbers in superscript)] at the human M2 mAChR, located at the interface between the orthosteric and allosteric binding sites of the receptor. We specifically focused on the role of the three tyrosine hydroxyl groups in the transition between the inactive and active conformations of the receptor by making phenylalanine point mutants. Single-point mutation at either of the three positions was sufficient to reduce the affinity of agonists by ∼100-fold for the M2 mAChR, whereas the affinity of antagonists remained largely unaffected. In contrast, neither of the mutations affected the efficacy of orthosteric agonists. When mutations were combined into double and triple M2 mAChR mutants, the affinity of antagonists was reduced by more than 100-fold compared with the wild-type M2 receptor. In contrast, the affinity of allosteric modulators, either negative or positive, was retained at all single and multiple mutations, but the degree of allosteric effect exerted on the endogenous ligand acetylcholine was affected at all mutants containing Y4267.39F. These findings will provide insights to consider when designing future mAChR ligands. SIGNIFICANCE STATEMENT Structural studies demonstrated that three tyrosine residues between the orthosteric and allosteric sites of the M2 muscarinic acetylcholine receptor (mAChR) had different hydrogen bonding networks in the inactive and active conformations. The role of hydroxyl groups of the tyrosine residues on orthosteric and allosteric ligand pharmacology was unknown. We found that hydroxyl groups of the tyrosine residues differentially affected the molecular pharmacology of orthosteric and allosteric ligands. These results provide insights to consider when designing future mAChR ligands.
ECG Modeling for Simulation of Arrhythmias in Time-Varying Conditions

The present article proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.
Sample Size and Power of Survival Trials in Group Sequential Design With Delayed Treatment Effect

ABSTRACT In study designs for randomized clinical trials with a survival endpoint, the log-rank test is commonly used with the treatment effect under a proportional hazards assumption. Recently, treatment effects in cancer immunotherapy trials have exhibited a delayed effect pattern with late separation of survival curves, raising challenges to the use of conventional study design hypotheses and analysis. In particular, when a trial with interim analyses is designed using a group sequential method, the expected treatment effect from a log-rank test statistic varies across analysis times and differs from the parameter specified under the alternative hypothesis. In this article, we present statistical analytical work that formulates a design including interim analyses with a survival endpoint under a delayed treatment effect alternative. Closed-form solutions are provided for calculating power and sample size over varying study/follow-up times for the group sequential, delayed treatment effect design. The analytical work is also presented graphically and simulations are conducted for validation.