bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive concerns are a risk factor for mortality in people with human immunodeficiency virus and COVID-19
Authors: Wilcox Douglas R. , Rudmann Emily A. , Ye Elissa , Noori Ayush , Magdamo Colin , Jain Aayushee , Alabsi Haitham , Foy Brody , Triant Virginia A. , Robbins Gregory K. , Westover M. Brandon , Das Sudeshna , Mukerji Shibani S. 
Published: May 2023

Background:
Data supporting dementia as a risk factor for COVID-19 mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. Dementia coding is not well-established for people with HIV (PWH), and its reliance may affect risk assessment.

Methods:
This retrospective cohort analysis of PWH with SARS-CoV-2 polymerase chain reaction positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by ICD-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death (OR [95% confidence interval]); models adjusted for VACS Index 2.0.

Results:
Sixty-four PWH were identified out of 14,129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared to PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, p = 0.01) and cognitive concerns (21.9% vs. 15.8%, p = 0.04). Death was more frequent in PWH (p < 0.01). Adjusted for VACS Index 2.0, dementia (2.4 [1.0–5.8], p = 0.05) and cognitive concerns (2.4 [1.1–5.3], p = 0.03) were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance (3.92 [0.81–20.19], p = 0.09); there was no association with dementia.

Conclusions:
Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with pre-existing cognitive deficits.
Effects of Pure Barre Exercise on Urinary Incontinence Symptoms: A Prospective Observational Cross-Sectional Study
Authors: Briskin Rebeccah S. , Luck Ali M. 
Published: May 2023

Importance
Pure Barre is a form of physical exercise using low-impact, high-intensity, pulsatile isometric movements that may serve as a treatment option for urinary incontinence.

Objective
The objective of this study was to measure the effects of the Pure Barre workout on urinary incontinence symptoms and sexual function.

Study Design
This was a prospective observational study of new, female Pure Barre clients with urinary incontinence. Eligible participants completed 3 validated questionnaires at baseline and at follow-up after 10 Pure Barre classes within 2 months. Questionnaires included the Michigan Incontinence Symptoms Index (M-ISI), the Pelvic Floor Distress Inventory-20, and the Female Sexual Function Index-6. Matched differences in domain questionnaire scores between baseline and follow-up were analyzed.

Results
All questionnaire domains significantly improved for all 25 participants after 10 Pure Barre classes. Median M-ISI severity domain scores decreased from 13 (interquartile range, 9–19) at baseline to 7 at follow-up (interquartile range, 3–10; P < 0.0001). Mean ± SD M-ISI urgency urinary incontinence domain scores decreased from 6.40 ± 3.06 to 2.96 ± 2.13 (P < 0.0001). Mean ± SD M-ISI stress urinary incontinence scores decreased from 5.24 ± 2.71 to 2.48 ± 1.58 (P < 0.0001). Mean ± SD Urinary Distress Inventory domain scores decreased from 42.17 ± 17.15 to 29.67 ± 13.73 (P < 0.0001). Matched rank sum analysis indicated increasing Female Sexual Function Index-6 scores from baseline to follow-up (P = 0.0022).

Conclusion
The Pure Barre workout may be an enjoyable, conservative management option that improves symptoms of urinary incontinence and sexual function.
Clean-Catch Urine Specimen More Likely to Be Contaminated After Vaginal Surgery for Pelvic Organ Prolapse
Authors: O’Meara Amanda , Abalyan Victoria , O’Sullivan David M. , Tunitsky-Bitton Elena 
Published: May 2023

Importance
Accurate diagnosis of urinary tract infection after pelvic organ prolapse (POP) surgery is essential to postoperative care.

Objective
Our aim was to determine the agreement between the urinalysis of a clean-catch versus a straight catheter urine specimen in women who underwent vaginal surgery for POP.

Study Design
This was a cross-sectional study evaluating patients after vaginal surgery for POP. A clean-catch and straight catheter urine specimen were collected at routine postoperative appointments. Routine urinalyses and urine cultures were performed for all patients. A urine culture yielding mixed urogenital flora (which includes Lactobacillus species), coagulase-negative staphylococci, and Streptococcus species was considered a contaminated result. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter at 3 weeks postoperatively was evaluated using weighted κ statistic.

Results
Fifty-nine participants enrolled. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter was poor (κ = 0.018). The urine culture was more likely to be contaminated from the clean-catch urine specimen than from the straight catheter urine specimen (53.7% vs 23.1%).
The positive and negative predictive values of leukocyte esterase on clean catch were 22.6% and 100%, respectively.

Conclusions
Diagnosing urinary tract infection based on contaminated urinalyses may lead to antibiotic overuse and misdiagnosis of postoperative complications. Our results can help educate health care partners and discourage the use of clean-catch urine specimens when assessing women who have recently undergone vaginal surgery.
Muscle Coordination Matters: Insights into Motor Planning using Corticospinal Responses during Functional Reaching
Authors: Augenstein Thomas E , Oh Seonga , Norris Trevor A , Mekler Joshua , Sethi Amit , Krishnan Chandramouli 
Published: May 2023

AbstractThe central nervous system (CNS) moves the human body by forming a plan in the primary motor cortex and then executing this plan by activating the relevant muscles. It is possible to study motor planning by using noninvasive brain stimulation techniques to stimulate the motor cortex prior to a movement and examine the evoked responses. Studying the motor planning process can reveal useful information about the CNS, but previous studies have generally been limited to single degree of freedom movements (e.g.,wrist flexion). It is currently unclear if findings in these studies generalize to multi-joint movements, which may be influenced by kinematic redundancy and muscle synergies. Here, our objective was to characterize motor planning in the cortex prior to a functional reach involving the upper extremity. We asked participants to reach for a cup placed in front of them when presented with a visual “Go Cue”.Following the go cue, but prior to movement onset, we used transcranial magnetic stimulation (TMS) to stimulate the motor cortex and measured the changes in the magnitudes of evoked responses in several upper extremity muscles (MEPs). We varied each participant’s initial arm posture to examine the effect of muscle coordination on MEPs. Additionally, we varied the timing of the stimulation between the go cue and movement onset to examine the time course of changes in the MEPs. We found that the MEPs in all proximal (shoulder and elbow) muscles increased as the stimulation was delivered closer to movement onset, regardless of arm posture, but MEPs in the distal (wrist and finger) muscles were not facilitated or even inhibited. We also found that facilitation varied with arm posture in a manner that reflected the coordination of the subsequent reach. We believe that these findings provide useful insight into the way the CNS plans motor skills.
Neutrophils actively swell to potentiate rapid migration
Authors: Nagy Tamas L , Strickland Evelyn , Weiner Orion D. 
Published: May 2023

AbstractWhile the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes is not known. We combine single cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.
Functional network analysis identifies multiple virulence and antibiotic resistance systems inStenotrophomonas maltophilia
Authors: Pinto Larina , Shastry Rajesh P , Alva Shivakiran , Rao R. Shyama Prasad , Ghate Sudeep D 
Published: May 2023

ABSTRACTStenotrophomonas maltophilia, an emerging multidrug-resistant opportunistic bacterium in humans is of major concern for immunocompromised individuals for causing pneumonia and bloodborne infections. This bacterial pathogen is associated with a considerable fatality/case ratio, with up to 100%, when presented as hemorrhagic fever. It is resistant to commonly used drugs as well as to antibiotic combinations. In-silico based functional network analysis is a key approach to get novel insights into virulence and resistance in pathogenic organisms. This study included the protein-protein interaction (PPI) network analysis of 150 specific genes identified for antibiotic resistance mechanism and virulence pathways. Eight proteins, namely,pilL,fliA,Smlt2260,Smlt2267,cheW,Smlt2318,cheZ, andfliMwere identified as hub proteins. Further docking studies of selected phytochemicals were performed against the identified hub proteins. Deoxytubulosine and Corosolic acid were found to be potent inhibitors of hub proteins of pathogenicS. maltophiliabased on protein-ligand interactive study. Further pharmacophore studies are warranted with these molecules to develop them as novel antibiotics againstS. maltophilia.
Growth and tension in explosive fruit
Authors: Mosca Gabriella , Eng Ryan , Adibi Milad , Yoshida Saiko , Lane Brendan , Bergheim Leona , Weber Gaby , Smith Richard S. , Hay Angela 
Published: May 2023

SummaryExploding seed pods of the common weedCardamine hirsutahave the remarkable ability to launch seeds far from the plant. The energy for this explosion comes from tension that builds up in the fruit valves. Above a critical threshold, the fruit fractures along its dehiscence zone and the two valves coil explosively, ejecting the seeds. Tension is commonly generated as seed pods dry, causing fruit tissues to deform. However, this does not happen inC. hirsuta.Instead, tension is produced by active contraction of growing exocarp cells in the outer layer of the fruit valves. Exactly how growth leads to contraction in these cells is unknown. Here we show that microtubule dynamics in the exocarp cell cortex control the specific orientation of cellulose microfibrils in the cell wall, and the consequent cellular growth pattern, which together drive contraction. We used mechanical modeling and simulations to show how tension emerges through the general process of plant cell growth, due to the highly anisotropic orientation of load-bearing cellulose microfibrils and their effect on cell shape. By explicitly defining the cell wall as multi-layered in our model, we discovered that a cross-lamellate pattern of cellulose microfibrils further enhances the developing tension in growing cells. Therefore, the interplay of cell wall properties with turgor-driven growth enables the fruit exocarp layer to develop sufficient tension to explode.
Natural variation of warm temperature-induced raffinose accumulation identifiesTREHALOSE-6-PHOSPHATE SYNTHASE 1as a modulator of thermotolerance
Authors: Reichelt Niklas , Korte Arthur , Krischke Markus , Mueller Martin J. , Maag Daniel 
Published: May 2023

AbstractHigh temperature stress limits plant growth and reproduction. Exposure to high temperature, however, also elicits a conserved physiological response, which protects plants from the damage evoked by heat. This response involves a partial reconfiguration of the plant metabolome including the accumulation of the trisaccharide raffinose. In this study, we explored the intra-specific variation of warm temperature-induced raffinose accumulation as a metabolic marker for temperature responsiveness with the aim to identify genes that contribute to plant thermotolerance. By combining raffinose measurements in 250Arabidopsis thalianaaccessions following a mild heat treatment with genome-wide association studies we identified five genomic regions that were associated with the observed trait variation. Subsequent functional analyses confirmed a causal relationship betweenTREHALOSE-6-PHOSPHATE SYNTHASE 1(TPS1) and warm temperature-dependent raffinose synthesis. Moreover, complementation of thetps1-1null mutant with functionally distinct TPS1 isoforms differentially affected carbohydrate metabolism under more severe heat stress. While higher TPS1 activity was associated with reduced endogenous sucrose levels and thermotolerance, disruption of trehalose 6-phosphate signalling resulted in higher accumulation of transitory starch and sucrose and was associated with enhanced heat resistance. Taken together, our findings suggest a role of trehalose 6-phosphate in thermotolerance most likely through its regulatory function in carbon partitioning and sucrose homeostasis.
Prediction of peptide hormones using an ensemble of machine learning and similarity-based methods
Authors: Kaur Dashleen , Arora Akanksha , Vigneshwar Palani , Raghava Gajendra P.S. 
Published: May 2023

AbstractPeptide hormones are genome-encoded signal transduction molecules released in multicellular organisms. The dysregulation of hormone release can cause multiple health problems and it is crucial to study these hormones for therapeutic purposes. To help the research community working in this field, we developed a prediction server that classifies hormonal peptides and non-hormonal peptides. The dataset used in this study was collected for both plants and animals from Hmrbase2 and PeptideAtlas databases. It comprises non-redundant 1174 hormonal and 1174 non-hormonal peptide sequences which were combined and divided into 80% training and 20% validation sets. We extracted a wide variety of compositional features from these sequences to develop various Machine Learning (ML) and Deep Learning (DL) models. The best performing model was logistic regression model trained on top 50 features which achieved an AUROC of 0.93. To enhance the performance of ML model, we applied Basic Local Alignment Search Tool (BLAST) to identify hormonal sequences using similarity among them, and motif search using Motif-Emerging and Classes-Identification (MERCI) to detect motifs present in hormonal and non-hormonal sequences. We combined our best performing classification model, i.e., logistic regression model with BLAST and MERCI to form a hybrid model that can predict hormonal peptide sequences accurately. The hybrid model is able to achieve an AUROC of 0.96, an accuracy of 89.79%, and an MCC of 0.8 on the validation set. This hybrid model has been incorporated on the publicly available website of HOPPred athttps://webs.iiitd.edu.in/raghava/hoppred/.
Human light meromyosin mutations linked to skeletal myopathies disrupt the coiled coil structure and myosin head sequestration
Authors: Carrington Glenn , Hau Abbi , Kosta Sarah , Dugdale Hannah F. , Muntoni Francesco , D’Amico Adele , Van den Bergh Peter , Romero Norma B. , Malfatti Edoardo , Vilchez Juan Jesus , Oldfors Anders , Pajusalu Sander , Õunap Katrin , Giralt-Pujol Marta , Zanoteli Edmar , Campbell Kenneth S. , Iwamoto Hiroyuki , Peckham Michelle , Ochala Julien 
Published: May 2023

AbstractMyosin heavy chains encoded byMYH7andMYH2are among the most abundant proteins in human skeletal muscle. After decades of intense research using a wide range of biophysical and biological approaches, their functions have begun to be elucidated. Despite this, it remains unclear how mutations in these genes and resultant proteins disrupt myosin structure and function, inducing pathological states and skeletal myopathies termed myosinopathies. Here, we have analysed the effects of several commonMYH7andMYH2mutations located in light meromyosin (LMM) using a broad range of approaches. We determined the secondary structure and filament forming capabilities of expressed and purified LMM constructs in vitro, performedin-silicomodelling of LMM constructs, and evaluated the incorporation of eGFP-myosin heavy chain constructs into sarcomeres in cultured myotubes. Using muscle biopsies from patients, we applied Mant-ATP chase protocols to estimate the proportion of myosin heads that were super-relaxed, X-ray diffraction measurements to estimate myosin head order and myofibre mechanics to investigate contractile function. We found that humanMYH7andMYH2LMM mutations commonly disrupt myosin coiled-coil structure and packing of filamentsin vitro; decrease the myosin super-relaxed statein vivoand increase the basal myosin ATP consumption; but are not associated with myofibre contractile deficits. Altogether, these findings indicate that the structural remodelling resulting from LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help in the design of future therapies for myosinopathies.
In silicodesign of DNA sequences forin vivonucleosome positioning
Authors: Routhier Ethienne , Pierre Edgar , Joubert Alexandra , Lancrey Astrid , Boulé Jean-Baptiste , Mozziconacci Julien 
Published: May 2023

AbstractThe computational design of synthetic DNA sequences with desired in vivo properties is gaining traction in the field of synthetic genomics. We propose here a computational method which combines a kinetic Monte Carlo framework with a deep mutational screening based on deep learning predictions. We apply our method to build regular nucleosome arrays with tailored nucleosomal repeat lengths (NRL) in yeast. Our design is validated in vivo by successfully engineering and integrating thousands of kilobases long tandem arrays of computationally optimized sequences which could accommodate NRLs much larger than the yeast natural NRL. This method delineates the key sequence rules for nucleosome positioning in yeast and is readily applicable to other sequence properties and other genomes.
Microhabitat acclimatization shifts physiological baselines and thermal tolerance of the symbiotic anemone,Anthopleura elegantissima
Authors: Ruggeri Maria , Million Wyatt C , Hamilton Lindsey , Kenkel Carly D 
Published: May 2023

AbstractContemporary organisms in extreme environments can give insight into how species will respond to environmental change. The intertidal forms an environmental gradient where stress increases with tidal height. Here, we explore the contribution of fixed genotypic and plastic environmental effects on thermal tolerance of the intertidal anemoneAnthopleura elegantissimaand its algal symbionts using a laboratory-based tank experiment. High intertidal anemones had lower baseline symbiont-to-host cell ratios under control conditions, but their symbionts had higher baseline maximum quantum yield compared to low intertidal anemone symbionts, despite identical symbiont communities. High intertidal anemones maintained greater maximum quantum yield and symbiont-to-host cell ratios under heat stress compared to low intertidal anemones, suggesting that high intertidal holobionts have greater thermal tolerance. However, thermal tolerance of clonal anemones acclimatized to different zones was not explained by tidal height alone, indicating emersion duration is not the sole environmental driver of physiological variation. Fixed genotypic effects also influenced physiological baselines, but did not modulate thermal tolerance, demonstrating thermal tolerance is largely driven by environmental history. These results indicate that this symbiosis is highly plastic and may be able to rapidly acclimatize to climate change, defying the convention that symbiotic organisms are more susceptible to environmental stress.
Cognitively Healthy Centenarians are genetically protected against Alzheimer’s disease specifically in immune and endo-lysosomal systems
Authors: Tesi Niccolo’ , van der Lee Sven , Hulsman Marc , van Schoor Natasja M. , Huisman Martijn , Pijnenburg Yolande , van der Flier Wiesje M. , Reinders Marcel , Holstege Henne 
Published: May 2023

AbstractBACKGROUNDAlzheimer’s Disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages beyond 100 years without cognitive decline. We aimed to uncover the genetic factors associated with such resilience against AD.METHODSGenome-Wide-Association-Studies (GWAS) identified 86 single-nucleotide-polymorphisms (SNPs) associated with AD-risk. We studied each SNP in 2,281 AD-cases, 3,165 middle-aged population controls, and 346 cognitively healthy centenarians, and we combined SNPs into Polygenic Risk Scores (PRS) for each individual. Finally, we investigated the functional properties of the SNPs enriched/depleted in centenarians usingsnpXplorer.RESULTSCentenarians were depleted with risk-increasing AD-SNPs and enriched with protective AD-SNPs. The PRS was more than 5-fold lower in centenarians compared to AD cases (p=7.69×10−71) and almost 2-fold lower compared to middle-aged population controls (p=5.83×10−17). The strongest protection was found inANKH, GRN, TMEM106B, SORT1, EPDR1, PLCG2, RIN3, CD2AP, andAPOEassociated alleles. As expected, the genetic protection was diluted in the offspring of the centenarians.DISCUSSIONBecoming a cognitively healthy centenarian is associated with a complex genetic protection against AD, which concentrates on an advantageous functioning of the endo-lysosomal and immune systems, and their effect on amyloid-clearance.