bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially Inappropriate Medication Use and the Hospitalization Rate among Thai Elderly Patients: a Retrospective Cohort Study
Authors: Varavithya Vorawee , Tirapat Chayanee , Rojpibulstit Penpitcha , Poovichayasumlit Panadda , Prasert Vanida , Vatcharavongvan Pasitpon 
Published: September 2021

AbstractPurposeTo examine the association between potentially inappropriate medications (PIMs) use and the hospitalization rate in elderly Thai patients.MethodsIn this retrospective cohort study, we collected the electronic medical data of elderly patients aged 60 years and older who visited the outpatient department (OPD) at Thammasat University Hospital in Thailand in 2015. The patients were categorized into PIM and non-PIM users according to the Beers 2019 criteria. We calculated descriptive statistics for demographic variables. We also examined the association between PIM use and various different factors with hospitalization rate during follow-up using log-binomial regression. We calculated the relative risk for association between PIM use and other factors with the hospitalization rate.ResultsWe collected data for a total of 32,261 patients. The majority of participants were female (59.65%) and had a mean age of 70.21 years (SD=7.88). Overall, 63.98% of the patients (n=20,641) were PIM users and 49.45% (n=15,952) received polypharmacy (≥5 medications). The most common PIM prescription was proton-pump inhibitors, which were 27.51% of all medications prescribed. We found that PIM use increased the risk of hospitalization by 1.31 times (adjusted RR=1.31, 95% CI: 1.21 – 1.41, p-value < 0.001). Other factors associated with a higher rate of hospitalizations included older age, male gender, polypharmacy, and a higher number of OPD visits.ConclusionPIMs were commonly prescribed to the elderly in the OPD, and were significantly associated with subsequent hospitalization. The provision of an alternative drug list can help physicians avoid prescribing PIMs to the elderly. If PIMs prescription is unavoidable, physicians should closely monitor patients for drug-related problems and deprescribe PIMs when they are no longer indicated.
The Role of Physical Environmental Characteristics and Intellectual Disability in Conduct Problem Trajectories Across Childhood: A Population-Based Cohort Study
Authors: Baird Alister , Papachristou Efstathios , Hassiotis Angela , Flouri Eirini 
Published: September 2021

AbstractBackgroundThe paucity of research investigating the role of the physical environment in the developmental progression of conduct problems and the potential moderating effects of intellectual disability (ID) is surprising, given the clinical relevance of elucidating environmental determinants of disruptive behaviours.AimsTo use data from a large UK cohort study to assess associations between physical environmental exposures, ID, and conduct problem trajectories.MethodThe sample included 8,168 Millennium Cohort Study children (1.9% with ID). Multilevel growth curve modelling was used to examine the role of physical environment characteristics in the developmental trajectories of conduct problems after adjustments for ID status.ResultsExposure to external environmental domains was not associated with differences in children’s conduct problems across development. Alternatively, internal aspects of the household environment: spatial density (b = 0.40, p<.001) and damp problems (b = 0.14, p<.001) were both significantly associated with increased trajectories. Various individual and familial covariates were positively associated with conduct problems over time, including: presence of ID (b = 0.96, p<.001), autism spectrum disorder (b = 1.18, p<.001), male sex (b = 0.26, p<.001), poverty (b = 0.19, p<.001), maternal depression (b = 0.65, p<.001), and non-nuclear family structure (b = 0.35, p<.001). Positive ID status appeared to moderate the effects of internal household spatial density, reporting a non-linear negative association with spatial density and conduct problems across development (b = -1.08, p<.01).ConclusionsOur findings highlight the potential harmful consequences of poor internal residential conditions on children’s development of disruptive behaviours.
How do we measure the adequacy of cancer pain management? Testing the performance of 4 commonly used measures and steps towards measurement refinement
Authors: Cabric Vanja , Harrison Rebecca , Gauthier Lynn R. , Graham Carol A , Gagliese Lucia 
Published: September 2021

AbstractAlthough pain is the most common and disabling cancer symptom requiring management, the best index of cancer pain management adequacy is unknown. While the Pain Management Index is most commonly used, other indices have included relief, satisfaction, and pain intensity. We evaluated their correlations and agreement, compared their biopsychosocial correlates, and investigated whether they represented a single construct reflecting the adequacy of cancer pain management in 269 people with advanced cancer and pain. Despite moderate-to-severe average pain in 52.8% of participants, 85.1% had PMI scores suggesting adequate analgesia, pain relief was moderate and satisfaction was high. Correlations and agreement were low-to-moderate, suggesting low construct validity. Although the correlates of pain management adequacy were multidimensional, including lower pain interference, neuropathic and nociceptive pain, and catastrophizing, shorter cancer duration, and greater physical symptoms, no single index captured this multidimensionality. Principal component analysis demonstrated a single underlying construct, thus we constructed the Adequacy of Cancer Pain Management from factor loadings. It had somewhat better agreement, however correlates were limited to pain interference and neuropathic pain. This study demonstrates the psychometric shortcomings of commonly used indices. We provide suggestions for future research to improve measurement, a critical step in optimizing cancer pain management.PerspectiveThe Pain Management Index and other commonly used indices of cancer pain management adequacy have poor construct validity. This study provides suggestions to improve the measurement of the adequacy of cancer pain management.
A linked mixture model of coronary atherosclerosis
Authors: Beheim Bret 
Published: September 2021

Background & ObjectivesCharacterizing the progression of coronary atherosclerosis is a critical public health goal. The most common quantitative summary, the CAC score, is modelled by a variety of statistical methods, both as a predictor of coronary events and as an outcome of behavioral and population-specific risk factors. Little attempt has been made, however, to ground these statistical models in the underlying physiology of arterial aging, which would allow us to describe the onset and growth of CAC over a patient's life.MethodsUsing a generative growth model for arterial plaque accumulation, we identify severe under-estimation in the age of initial onset and rate of progression (doubling time) of CAC growth with standard ln(CAC + 1) or ln(CAC | CAC > 0) models, and use this growth model to motivate new statistical approaches to CAC using logistic and log-linear mixture regressions. We compare statistical models directly by computing their average parameter biases using 540 growth trajectory simulations (113,760 patients, 268,200 observations).ResultsWhile all models used can successfully estimate the influence of risk factors with minimal bias, we demonstrate substantial improvements in predictive accuracy in the timing of CAC onset and progression with logistic regression and linked hurdle-lognormal mixture regression, compared with standard ln(CAC + 1) or ln(CAC | CAC > 0) models.ConclusionsUsing models that can account for patient-specific onset and progression rates, accurate descriptions of CAC trajectories can be made even in cross-sectional (single scan per patient) designs, with substantial clinical and epidemiological utility.
Bodily ownership of an independent supernumerary limb: An exploratory study
Authors: Umezawa Kohei , Suzuki Yuta , Ganesh Gowrishankar , Miyawaki Yoichi 
Published: September 2021

AbstractCan our brain perceive a sense of ownership towards an independent supernumerary limb; one that can be moved independently of any other limb and provides its own independent movement feedback? Following the rubberhand illusion experiment, a plethora of studies has shown that the human representation of ‘self’ is very plastic. But previous studies have almost exclusively investigated ownership towards ‘substitute’ artificial limbs, which are controlled by the movements of a real limb and/or limbs from which non-visual sensory feedback is provided on an existing limb. Here, to investigate whether the human brain can own an independent artificial limb, we first developed a novel independent robotic ‘sixth finger.’ We allowed participants to train using the finger and examined whether it induced changes in the body representation using behavioral as well as cognitive measures. Our results suggest that unlike a substituted artificial limb (like in the rubber hand experiment), it is more difficult for humans to perceive a sense of ownership towards an independent limb. However, ownership does seem possible, as we observed clear tendencies of changes in the body representation that correlated with the cognitive reports of the sense of ownership. Our results provide the first evidence to show that an independent supernumerary limb can be embodied by the human brain.
The secrets to domestic bliss – Partner fidelity and environmental filtering preserve stage-specific turtle ant gut symbioses for over 40 million years
Authors: Hu Yi , D’Amelio Catherine L. , Béchade Benoît , Cabuslay Christian S. , Sanders Jon G. , Price Shauna , Fanwick Emily , Powell Scott , Moreau Corrie S. , Russell Jacob A. 
Published: September 2021

AbstractBackgroundGut microbiomes can vary across development, a pattern often found for insects with complete metamorphosis. With varying nutritional need and distinct opportunities for microbial acquisition, questions arise as to how such ‘holometabolous’ insects retain helpful microbes at larval and adult stages. Ants are an intriguing system for such study. In a number of lineages adults digest only liquid food sources, while larvae digest solid foods. Like some other social insects, workers and soldiers of some ant species engage in oral-anal trophallaxes, enabling microbial transfer among siblings. But do queens, the typical colony founding caste, obtain symbionts through such transfer? Does this enable transgenerational symbiont passage? And does the resulting partner fidelity promote the evolution of beneficial symbionts? Furthermore, how might such adult-centric biology shape larval microbiomes? To address these questions, we characterized symbiotic gut bacteria across 13 species of Cephalotes turtle ants, with up to 40-million years of divergence. Adding to the prior focus on workers we, here, study underexplored castes and stages including queens, soldiers, and larvae, by performing 16S rRNA qPCR, amplicon sequencing, and phylogenetic classification.ResultsWe show that adult microbiomes are conserved across species and largely across castes. Nearly 95% of the bacteria in adults have, thus far, been found only in Cephalotes ants. Furthermore, the microbiomes from most adults exhibit phylosymbiosis, a trend in which microbiome community similarity recapitulates patterns of host relatedness. Additionally, an abundant, adult-enriched symbiont cospeciates with some Cephalotes. Evidence here suggests that these partner fidelity patterns extend from transgenerational symbiont transfer through alate gyne dispersal and subsequent colony-founding by queens. Like adults, larvae of Cephalotes species exhibit strong microbiome conservation. Phylosymbiosis patterns are weaker, however, with further evidence elevating environmental filtering as a primary mechanism behind such conservation. Specifically, while adult-enriched symbionts are found in most larvae, symbionts of older larvae are highly related to free-living bacteria from the Enterobacteriaceae, Lactobacillales, and Actinobacteria.ConclusionsOur findings suggest that both partner fidelity and conserved environmental filtering drive stable, stage-specific, social insect symbioses. We discuss the implications for our broader understanding of insect microbiomes, and the means of sustaining a beneficial microbiome.
Insertive vaginal sex has a profound impact on the penile immune correlates of HIV susceptibility
Authors: Mohammadi Avid , Bagherichimeh Sareh , Choi Yoojin , Fazel Azadeh , Tevlin Elizabeth , Huibner Sanja , Shao Eric , Zuanazzi David , Prodger Jessica , Good Sara V , Tharao Wangari , Kaul Rupert 
Published: September 2021

ABSTRACTThe penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n=30) or condom-protected (n=8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners’ cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.Author summaryIn heterosexual men, the penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition. Levels of inflammatory cytokines in the coronal sulcus are associated with an increased HIV risk, and we hypothesized that these may be altered after insertive penile sex. Therefore, we designed the Sex, Couples and Science Study (SECS study) to define the impact of penile-vaginal sex on the penile immune correlates of HIV susceptibility. We found that multiple coronal sulcus cytokines increased dramatically and rapidly after sex, regardless of condom use, with a return to baseline levels by 72 hours. The changes observed after condomless sex were strongly predicted by cytokine concentrations in the vaginal secretions of the female partner, and were similar in circumcised and uncircumcised men. We believe that these findings have important implications for understanding the immunopathogenesis of penile HIV acquisition; in addition, they have important implications for the design of clinical studies of penile HIV acquisition and prevention.
Size-selective mortality fosters ontogenetic changes in collective risk-taking behaviour in zebrafish,Danio rerio
Authors: Roy Tamal , Arlinghaus Robert 
Published: September 2021

AbstractSize-selective mortality is common in fish populations and can operate either in a positive size-selective fashion or be negatively size-selective. Through various mechanisms (like genetic correlations among behaviour and life-history traits or direct selection on behaviour co-varying with growth rate or size-at-maturation), both positive- and negative size-selection can result in evolutionary changes in behavioural traits. Theory suggests that size-selection alone favours boldness, but little experimental evidence exists about whether and to what extent size-selection can trigger its evolution. Here we investigated the impact of size-selective mortality on boldness across ontogeny using three experimental lines of zebrafish (Danio rerio) generated through positive (large-harvested), negative (small-harvested) and random (control line) size-selective mortality for five generations. We measured risk-taking during feeding (boldness) under simulated aerial predation threat and in presence of a live cichlid. We found that boldness decreased with ontogenetic age under aerial predation threat, and the small-harvested line was consistently bolder than controls. Collective personality emerged post larval stages among the selection lines. In presence of a cichlid, the large-harvested line was bolder at the highest risk of predation. The large-harvested line showed higher variability and plasticity in boldness across life stages and predation risks. Collectively, our results demonstrate that size-selective harvesting may evolutionarily alter risk-taking tendency. Size-selection alone favours boldness when selection acts on small fish. Selection typical of fisheries operating on large fish favours boldness at the highest risk of predation and increases behavioural variability and plasticity. There was no evidence for positive size-selection favouring evolution of shyness.
Potential Key Genes Associated with Stroke types and its subtypes: A Computational Approach
Authors: Das Gourab , Kumar Pradeep 
Published: September 2021

AbstractTo investigate prospective key genes and pathways associated with the pathogenesis and prognosis of stroke types along with subtypes. Human genes using genome assembly build 38 patch release 13 with known gene symbols through NCBI gene database (https://www.ncbi.nlm.nih.gov/gene) were fetched. PubMed advanced queries were constructed using stroke-related keywords and associations were calculated using Normalized pointwise mutual information (nPMI) between each gene symbol and queries. Genes related with stroke risk within their types and subtypes were investigated in order to discover genetic markers to predict individuals who are at the risk of developing stroke with their subtypes. A total of 2,785 (9.4%) genes were found to be linked to the risk of stroke. Based on stroke types, 1,287 (46.2%) and 376 (13.5%) genes were found to be related with IS and HS respectively. Further stratification of IS based on TOAST classification, 86 (6.6%) genes were confined to Large artery atherosclerosis; 131 (10.1%) and 130 (10%) genes were related with the risk of small vessel disease and Cardioembolism subtypes of IS. Besides, a prognostic panel of 9 genes signature consisting of CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, MTHFR, PDE4D, HDAC9, and ZHFX3 can be treated as a diagnostic marker to predict individuals who are at the risk of developing stroke with their subtypes.
Dysregulation of the Tweak/Fn14 pathway in skeletal muscle of spinal muscular atrophy mice
Authors: Meijboom Katharina E. , McFall Emily , Anthony Daniel , Edwards Benjamin , Kubinski Sabrina , Hazell Gareth , Ahlskog Nina , Claus Peter , Davies Kay E. , Kothary Rashmi , Wood Matthew J.A. , Bowerman Melissa 
Published: September 2021

ABSTRACTSpinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn-/-;SMN2 and the less severe Smn2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. Here, we report significantly dysregulated expression of the TWEAK/Fn14 pathway during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak-/- and Fn14-/- mice revealed dysregulated myopathy, myogenesis and glucose metabolism pathways as a common skeletal muscle feature, and providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, a pharmacological intervention (Fc-TWEAK) to upregulate the activity of the TWEAK/Fn14 pathway improved disease phenotypes in the two SMA mouse models. Our study provides novel mechanistic insights into the molecular players that contribute to muscle pathology in SMA and into the role of the TWEAK/Fn14 pathway in developing muscle.
Identification of a discrete neuronal circuit that relays insulin signaling into the brain to regulate glucose homeostasis
Authors: Mehdi Mouna El , Takhlidjt Saloua , Devère Mélodie , Arabo Arnaud , Le Solliec Marie-Anne , Maucotel Julie , Bénani Alexandre , Nedelec Emmanuelle , Duparc Céline , Lefranc Benjamin , Leprince Jérôme , Anouar Youssef , Prévost Gaëtan , Chartrel Nicolas , Picot Marie 
Published: September 2021

Abstract26RFa (QRFP) is a biologically active peptide that regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity at the periphery. 26RFa is also produced by a neuronal population localized in the hypothalamus. In the present study, we have investigated whether the 26RFa neurons may be involved in the hypothalamic regulation of glucose homeostasis. Our data indicate that 26RFa, i.c.v. injected, induces a robust antihyperglycemic effect associated with an increase of insulin production by the pancreatic islets. In addition, we found that insulin strongly stimulates 26RFa expression and secretion by the hypothalamus. RNAscope experiments revealed that neurons expressing 26RFa in the lateral hypothalamic area and the ventromedial hypothalamic nucleus also express the insulin receptor and that insulin induces the expression of 26RFa in these neurons. Concurrently, we show that the central antihyperglycemic effect of insulin is abolished in presence of a 26RFa receptor (GPR103) antagonist as well as in mice deficient for 26RFa. Finally, our data indicate that the hypothalamic 26RFa neurons are not involved in the central inhibitory effect of insulin on hepatic glucose production, but mediate the central effects of the hormone on its own peripheral production.To conclude, in the present study we have identified a novel actor of the hypothalamic regulation of glucose homeostasis, the 26RFa/GPR103 system and we provide the evidence that this neuronal peptidergic system is a key relay for the central regulation of glucose metabolism by insulin.