bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Impacts of Alcohol and Other Drug Use on HIV Care Among Older African American Adults in Kentucky: A Constructivist Grounded Theory Study
Authors: Harris Lesley M. , Silverstein Sydney M. , Crawford Timothy N. , Kerr Jelani C. , Ball Diana
Published: December 2021

This grounded theory study examined the use of alcohol and other drugs (AOD) on the management of HIV disease among 27 older African Americans (≥50 years). Interview transcripts were analyzed using constructivist grounded theory analytic techniques. Participants reported facing (a) environmental impacts of AOD use and (b) discrimination from the health care system. The analysis revealed six phases of AOD use, occurring at various stages of the HIV care continuum: (a) linking AOD use as the cause of HIV diagnosis, (b) having AOD use facilitate denial of HIV, (c) experiencing problematic use as a barrier to care engagement, (d) “testing the waters,” (e) relying on AIDS service organizations and medical providers, and (f) changing or maintaining patterns of AOD use to maintain engagement with care. Recommendations include assessing a patient's AOD use in relationship to the care continuum to evaluate patients' experiences and barriers within systems of care.
Cleft Palate and Vascular Malformation in a Pediatric Patient With PIK3CA-related Overgrowth Spectrum
Authors: Das Rishub K. , Borst Alexandra J. , Phillips James D.
Published: December 2021

Phosphoinositide-3-kinase, catalytic, alpha polypeptide-related overgrowth spectrum (PROS) encompasses a heterogenous group of disorders involving somatic mutations in the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. The categories of PROS diseases continue to change as unique presentations and phenotype-genotype correlations are reported. These mutations result in progressive, segmental overgrowth of the affected tissue. Vascular malformations are common in PROS and represent a significant social and medical burden to patients, and in some cases, an increased risk for malignancy. Cleft palate, however, has not been reported. Herein, we describe a case of a 13-year-old girl with a variant of unknown significance in the PIK3CA gene who presents with a large capillary malformation, cleft palate, and right-sided hemihypertrophy.
Analysis of Reported Adverse Events With Colonic Stents
Authors: Ramai Daryl , DeLuca Matthew , Facciorusso Antonio , Ofosu Andrew , Girotra Mohit , Tabibian James H. , Rodrigues-Pinto Eduardo , Adler Douglas G. , Barakat Monique T.
Published: December 2021

Background:

Colonic stents are indicated for preoperative and palliative decompression of large bowel obstruction. We aim to investigate post Food and Drug Administration (FDA) approval outcomes associated with colonic stents.

Materials and Methods:

We analyzed postmarketing surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database from January 2011 to December 2020.

Results:

During the study period, 691 device issues and 742 patient complications were identified. The number of adverse events reported to the FDA mildly increased from 6.40% in 2011 to 7.4% in 2020. Most device complications were due to a positioning problem (n=201, 29%), followed by device break (n=60, 8.6%), delamination (n=41, 6.3%), and migration or expulsion device (n=38, 5.55%). A number of reports described an unclassified adverse event without specifying device or operator problem (n=141, 20.3%). The most reported patient adverse events were perforation (n=150, 20.1%), death (n=47, 6.3%), abdominal pain/discomfort (n=27, 3.6%), and peritonitis (n=24, 3.2%).

Conclusion:

Findings from the MAUDE database highlight rare but important patient and device complications which endoscopists and referring providers should be aware of before consideration for colonic stent placement.
Less Emergency Department Abdominopelvic Computed Tomography for Patients With Crohn’s Disease
Authors: Riskin Geuz Kinneret S. , Schwartz Doron
Published: December 2021

Background:

In recent years, the use of abdominal pelvic computed tomography (APCT) in the emergency department (ED) for patients with Crohn’s disease (CD) has risen steadily. Thus, exposing these patients to recurrent radiation, despite studies showing that only 30% to 40% had significant findings in ED APCT.

Goal:

Our aim was to find clinical and laboratory variables that can predict substantial findings on ED APCT, which may require invasive intervention.

Methods:

We analyzed ED visits of patients with known CD that underwent an emergent APCT for gastrointestinal complaints, over a 10-year period. Patients with positive and negative findings in the APCT were compared in order to evaluate independent effects of different variables, including patients’ characteristics, CD history, ED complaints, and laboratory tests.

Results:

In 44% of 183 ED visits, there were significant findings on ED APCT, however, only 22% of them underwent invasive intervention. Laboratory tests: C-reactive protein >50 mg/L, neutrophil count >75%, platelet count >350×109/L, and ileocolon location at diagnosis were all positive predicting factors. Whereas, smoking or ED complaints of diarrhea/fever reduced the risk for significant findings.

Conclusions:

Using the 7 most significant predicting factors, we built an easy to use scoring system—Crohn Assessment Tool for CT upon Hospitalization (CATCH) for ED clinicians. This scoring system could have prevented unnecessary ED APCT from 42% of the patients in our study, without missing those who required invasive intervention.
Validation of the IBD-Disk in a Portuguese cohort
Authors: Silva Mendes Sofia , Ferreira Patrícia , Antunes Pedro , Gonçalves Margarida , Leal Tiago , Gonçalves Bruno , Rebelo Ana , Arroja Bruno , Caetano Ana C. , Gonçalves Raquel , Soares João B.
Published: December 2021

Objective

The aim of this study was to validate the IBD-Disk in a Portuguese cohort according to the COnsensus-based Standards for the selection of the health Measurement INstruments (COSMIN) recommendations.

Methods

After translation of the original IBD-Disk to Portuguese, a group of IBD patients was invited to complete the IBD-Disk at baseline (T0), after 1-4 weeks (T1) and after more than 3 months (T2), from July 2020 to February 2021. At T0 and T2, the patients also completed the IBD Disability Index. We evaluated reliability (internal consistency, test-retest, interrater reliability and measurement error), construct validity, responsiveness, interpretability of IBD-Disk, sociodemographic and clinical factors associated with IBD-Disk.

Results

At T0, 154 patients (107 - Crohn’s disease; 46 - ulcerative colitis) completed the IBD-Disk; 1 - IBD-unclassified). At T1 and T2, 64 and 114 patients repeated the questionnaire, respectively. Factor analysis confirmed the unidimensionality of the scale and reduced the final version to 10 items. Internal consistency was excellent with a Cronbach’s α of 0.916. The intraclass correlation coefficient was 0.95 for test-retest (T0 and T1). To evaluate construct validity, the IBD-Disk was compared with the IBD Disability Index and Manitoba IBD Index with a significative positive correlation (r = 0.850 and r = 0.459, respectively; P < 0.001 for both). IBD-Disk scores ranged from 0 to 93 with a mean of 38.18 ± 25.39. Female sex, professional inactivity, longer IBD duration and clinical activity were associated with significantly higher IBD-Disk scores.

Conclusion

The Portuguese version of IBD-Disk is a reliable and valid tool to assess disability in Portuguese IBD patients.
Lipids and brain inflammation in APOE4-associated dementia
Authors: Duro Marlon V. , Ebright Brandon , Yassine Hussein N.
Published: December 2021

Purpose of review

To highlight recent developments in studying mechanisms by which the apolipoprotein E4 (APOE4) allele affects the metabolism of brain lipids and predisposes the brain to inflammation and Alzheimer's disease (AD) dementia.

Recent findings

APOE4 activates Ca2+ dependent phospholipase A2 (cPLA2) leading to changes in arachidonic acid (AA), eicosapentaenoic acid and docosahexaenoic acid signaling cascades in the brain. Among these changes, the increased conversion of AA to eicosanoids associates with sustained and unresolved chronic brain inflammation. The effects of APOE4 on the brain differ by age, disease stage, nutritional status and can be uncovered by brain imaging studies of brain fatty acid uptake. Reducing cPLA2 expression in the dementia brain presents a viable strategy that awaits to be tested.

Fatty acid brain imaging techniques can clarify how changes to brain polyunsaturated fatty acid metabolism during the various phases of AD and guide the development of small molecules to mitigate brain inflammation.
Learning Longitudinal Patterns and Subtypes of Pediatric Crohn Disease Treated With Infliximab via Trajectory Cluster Analysis
Authors: Chen Andrew , Stein Ronen , Baldassano Robert N. , Huang Jing
Published: December 2021

Background:

The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records.

Methods:

We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C‐reactive protein (CRP). We compared patient characteristics, biomarker for disease activity, and long‐term surgical outcomes across subgroups. Cox regression models were used to evaluate the added value of the subgroup classification to baseline phenotype and location in prediction of long‐term surgical outcomes.

Results:

We identified three subgroups of patients with differential relapse‐and‐remission profiles (n = 33, 65 and 197 from subgroup 1 to 3), which represented patients with a higher risk of infliximab non‐response, with infliximab response but with occasional disease flares, and patients with long‐term response. Patients with the best treatment response had a significantly lower frequency of complicated disease phenotypes (P = 0.01), including perianal involvement (P = 0.05), lower baseline CRP (P < 0.01) and calprotectin (P = 0.01), and lowest risk of IBD‐related gastrointestinal surgery within 10 years of starting treatment (P < 0.01).

Conclusions:

Readily available longitudinal data from electronic health records can be leveraged to provide deeper characterization of treatment response in pediatric CD.
Student-Centered Reflection During Debriefing
Authors: Nagle Amy , Foli Karen J.
Published: December 2021

Background:

Guided reflection during a debriefing after the simulation is a critical component of learning and is essential for clinical judgment development. However, the literature describing student-centered reflection during debriefing is only beginning to emerge.

Purpose:

This study aimed to explore concordance between student-centered reflection concept characteristics and describe students' experiences related to reflection during an optimal simulation debriefing.

Methods:

This was a descriptive, mixed-methods study.

Results:

Quantitative responses (N = 175; 67% response rate) confirmed participants' concordance with student-centered reflection concept analysis attributes, antecedents, and consequences. Analysis of open-ended questions highlighted internal and external factors influencing students' reflections. A recurring theme was the importance of faculty and peers in creating a safe, supportive environment for reflections.

Conclusions:

Findings support the concordance of student-centered reflection and provide valuable insights into the internal and external factors influencing this reflection.
Dynamic Reconstruction of the Lower Lip With Free Functioning Gracilis Muscle Transfer
Authors: Krakowczyk Łukasz , Opyrchał Jakub , Bula Daniel , Wierzgoń Janusz , Szymczyk Cezary , Maciejewski Adam
Published: December 2021

The restoration of large full-thickness lip defects still remains a formidable challenge for the reconstructive surgeons. Traumatic injuries, infections and tumors (primarily squamous cell carcinoma) are the most common source of the lip defects. Lower lips are more important in providing oral competence, unfortunately throughout the life-time they are significantly more exposed to ultraviolet radiation and thus are the most common site for the lip cancers (89%). This type of defect requires a complex reconstruction of an adequate sphincter function, defined vermilion, proper oral lining and sufficient mouth opening. To maintain the oral competence, it is of paramount importance to restore the function of orbicularis oris, which principally composes the body of the lip. Currently, the dynamic reconstructions are gaining considerable interest. They enables not only improvement of appearance but also a restoration of function and preservation of health-related quality of life. The use of the free gracilis muscle transfer to reconstruct the lower lip and its dynamic character in contrast to other, static reconstructions can provide the sufficient movement of the lower lip, which does not depend on function of other mimic muscles as it becomes an independent motor unit with its own neurotization. In our opinion the free functioning gracilis muscle flap, due to its anatomic and functional features as well as low-rate donor-site morbidity is the worth considering option for a lower lip reconstruction.
The Use of Computer-Guided Half Propeller Genioplasty for the Correction of Mandibular Asymmetry (A Mandibular Orthognathic Surgery Without a Condylar Intervention Technical Strategy)
Authors: El Dien Hany Hossam , Zaki Ahmed Hany , El Hadidi Yasser Nabil , Gaber Ramy Mohamed
Published: December 2021

Introduction:

Mandibular asymmetry is a facial deformity that results from multiple causes; among these are growth deficiency like hemifacial microsomia and growth excess as in condylar hyperplasia. The facial asymmetry caused by condylar hyperplasia has been treated over the years with different surgical and nonsur-gical modalities dependent on the age of the patient and the severity of the condition. The authors in this article introduce a modified version of the propeller genioplasty technique.

Materials and Methods:

A new surgical technique “modified propeller genioplasty” is introduced for the management of facial asymmetry. Virtual surgical planning of the osteotomies and segment repositioning was done virtually. A cutting guide, positioning guides and 3D model of the corrected chin were 3D printed, to facilitate replication ofthe virtually planned osteotomies, prebending of plates, and segment repositioning.

Results:

The esthetically accepted result was achieved using this technique with minimal postoperative complications.

Conclusions:

The technique appeared to be accurate, simple, and more cost efficient when compared to patient-specific plates.
ETS-Related Gene Activation Preserves Adherens Junctions and Permeability in Microvascular Endothelial Cells
Authors: Tharakan Binu , Hunter Felicia A. , Muthusamy Saravanakumar , Randolph Sonya , Byrd Crystal , Rao Veena N. , Reddy E Shyam P. , Childs Ed. W.
Published: December 2021

ERG (ETS-related gene) is a member of the ETS (Erythroblast-transformation specific) family of transcription factors abundantly present in vascular endothelial cells. Recent studies demonstrate that ERG has important roles in blood vessel stability and angiogenesis. However, it is unclear how ERG is potentially involved in microvascular barrier functions and permeability. A wide variety of diseases and clinical conditions including trauma-hemorrhagic shock and burn injury are associated with microvascular dysfunctions, which causes excessive microvascular permeability, tissue edema and eventually, multiple organ dysfunction and death. The main purpose of this study was to determine the specific role of ERG in regulating microvascular permeability in human lung microvascular endothelial cells (HLMEC) and to evaluate if exogenous ERG will protect the barrier. The HLMECs were grown on Transwell inserts as monolayers and were transfected with ERG CRISPR/cas9 knockdown plasmid, ERG CRISPR activation plasmid, recombinant ERG protein or their respective controls. Recombinant vascular endothelial growth factor (VEGF) was used as an inducer of permeability for evaluating the effect of ERG activation on permeability. Changes in barrier integrity and permeability were studied using monolayer permeability assay and immunofluorescence of adherens junction proteins (VE-cadherin and β-catenin) respectively. CRISPR/cas9-based ERG knockdown as well as VEGF treatment induced monolayer hyperpermeability, VE-cadherin, and β-catenin junctional relocation and cytoskeletal F-actin stress fiber formation. CRISPR based ERG activation and recombinant ERG transfection attenuated VEGF-induced monolayer hyperpermeability. ERG activation preserved the adherens junctions and cytoskeleton. These results demonstrate that ERG is a potent regulator of barrier integrity and permeability in human lung microvascular endothelial cells and endogenously or exogenously enhancing ERG provides protection against barrier dysfunction and hyperpermeability.
A scoping review of nontechnical skill assessment tools to evaluate trauma team performance
Authors: Bhangu Avneesh , Stevenson Christina , Szulewski Adam , MacDonald Aidan , Nolan Brodie
Published: December 2021

BACKGROUND

The objective of this scoping review was to identify assessment tools of trauma team performance (outside of technical skills) and assess the validity and reliability of each tool in assessing trauma team performance.

METHODS

We searched Embase, Cochrane Library, Web of Science, Ovid Medline, and Cumulative Index to Nursing and Allied Health Literature from inception to June 1, 2021. English studies that evaluated trauma team performance using nontechnical skill assessment tools in a simulation or real-world setting were included. Studies were assessed by two independent reviewers for meeting inclusion/exclusion criteria. Data regarding team assessment tools were extracted and synthesized into behavior domains. Each tool was then assessed for validity and reliability.

RESULTS

The literature search returned 4,215 articles with 29 meeting inclusion criteria. Our search identified 12 trauma team performance assessment tools. Most studies were conducted in the United States (n = 20 [69%]). Twenty studies (69%) assessed trauma team performance in a simulation setting; Team Emergency Assessment Measure (TEAM) and Trauma Nontechnical Skills Scale (T-NOTECHS) were the only tools to be applied in a simulation and real-world setting. Most studies assessed trauma team performance using video review technology (n = 17 [59%]). Five overarching themes were designed to encompass behavioral domains captured across the 12 tools: (1) Leadership, (2) Communication, (3) Teamwork, (4) Assessment, and (5) Situation Awareness. The reliability and validity of T-NOTECHS were investigated by the greatest number of studies (n = 13); however, TEAM had the most robust evidence of reliability and validity.

CONCLUSION

We identified 12 trauma team performance tools that assessed nontechnical skills to varying degrees. Trauma Nontechnical Skills Scale and TEAM tools had the most evidence to support their reliability and validity. Considering the limited research in the impact of trauma team performance on patient outcomes, future studies could use video review technology in authentic trauma cases to further study this important relationship.

LEVEL OF EVIDENCE

Systematic reviews and meta-analyses, level IV.
Comparative transcriptome analysis and CRISPR/Cas9 gene editing reveal that E4BP4 mediates lithium upregulation of
Per2
expression
Authors: Zhou Qin , Wang Kankan , Qiu Jiameng , Zhu Di , Tian Tian , Zhang Yunfei , Qin Ximing
Published: December 2021

Bipolar disorder (BPD) is a psychiatric disorder characterized by alternate episodes of mania and depression. Disruption of normal circadian clock and abnormal sleep cycles are common symptoms of BPD patients. Lithium salt is currently an effective clinical therapeutic drug for BPD. Animal and cellular studies have found that lithium salt can upregulate the expression of the clock gene
Per2
, but the mechanism is unknown. We aim to understand the mechanism underlying the
Per2
upregulation by lithium treatment. By taking approaches of both comparative transcriptome analysis and comparative qPCR analysis between human and murine cells, Lumicycle assay, luciferase assay and RT-qPCR assay showed that lithium could significantly upregulate the expression of
Per2
in both mouse and human cells, and significantly inhibit the expression of
E4bp4
, which encodes a transcriptional inhibitor of
Per2
. After knocking out the cis-element upstream on the
Per2
promoter that responds to E4BP4, the upregulation effect on
Per2
by lithium disappeared. When
E4bp4
gene was knocked out, the upregulation effect on
Per2
by lithium salt disappeared. This study has found that lithium upregulates
Per2
expression by reducing the expression of transcription factor E4BP4, but the mechanism of lithium salt downregulation of E4BP4 remains to be further studied. Our study provides a new therapeutic target and approaches for treating BPD.
Host-derived lipids from tuberculous pleurisy impair macrophage
microbicidal-associated metabolic activity
Authors: Franco José Luis Marín , Genoula Melanie , Corral Dan , Duette Gabriel , Ferreyra Malena , Maio Mariano , Dolotowicz María Belén , Aparicio-Trejo Omar Emiliano , Patiño-Martínez Eduardo , Fuentes Federico , Soldan Vanessa , Moraña Eduardo José , Palmero Domingo , Ostrowski Matías , Schierloh Pablo , Sánchez-Torres Carmen , Hernández-Pando Rogelio , Pedraza-Chaverri José , Rombouts Yoann , Layre Emilie , Hudrisier Denis , Vérollet Christel , Neyrolles Olivier , Sasiain María Del Carmen , Lugo-Villarino Geanncarlo , Balboa Luciana
Published: December 2021

Mycobacterium tuberculosis (Mtb) regulates the
macrophage metabolic state to thrive in the host. Yet, the responsible
mechanisms remain elusive. Macrophage activation towards the microbicidal (M1)
program depends on the HIF-1 α-mediated metabolic shift from oxidative
phosphorylation towards glycolysis. Here, we asked whether a tuberculosis (TB)
microenvironment changes the M1 macrophage metabolic state. We exposed M1
macrophages to the acellular fraction of tuberculous pleural effusions (TB-PE),
and found lower glycolytic activity, accompanied by elevated levels of oxidative
phosphorylation and bacillary load, compared to controls. The host-derived lipid
fraction of TB-PE drove these metabolic alterations. HIF-1α stabilization
reverted the effect of TB-PE by restoring M1 metabolism. As a proof-of-concept,
Mtb-infected mice with stabilized HIF-1α displayed lower bacillary loads and a
pronounced M1-like metabolic profile in alveolar macrophages. Collectively, we
demonstrate that host-derived lipids from a TB-associated microenvironment alter
the M1 macrophage metabolic reprogramming by hampering HIF-1α functions, thereby
impairing control of Mtb infection.
Aging associated altered response to intracellular bacterial infections and
its implication on the host
Authors: Fernandes Sheryl E. , Singh Alakesh , Rajmani R.S. , Jhunjhunwala Siddharth , Saini Deepak K.
Published: December 2021

The effects of senescence and aging on geriatric diseases has been well
explored but how these influence infections in the elderly have been scarcely
addressed. Here, we show that several innate immune responses are elevated in
senescent cells and old mice, allowing them to promptly respond to bacterial
infections. We have identified higher levels of iNOS as a crucial host response
and show that p38 MAPK in senescent cells acts as a negative regulator of iNOS
transcription. In old mice, however the ability to impede bacterial
proliferation does not correlate with increased survival as elevated immune
responses persist unabated eventually affecting the host. The use of
anti-inflammatory drugs that could consequently be recommended also decreases
iNOS disarming the host of a critical innate immune response. Overall, our study
highlights that infection associated mortality in the elderly is not merely an
outcome of pathogen load but is also influenced by the host’s ability to resolve
inflammation induced damage.

Summary statement

Using cellular models and old mice we demonstrate the effect of aging on
host response to bacterial infections. Aged systems mount a more effective
anti-bacterial innate immune response but its persistence results in
mortality of the host.
Interdomain interactions regulate the localization of a lipid transfer
protein at ER-PM contact sites
Authors: Basak Bishal , Krishnan Harini , Raghu Padinjat
Published: December 2021

During phospholipase C-β (PLC-β) signalling in
Drosophila photoreceptors, the
phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid
transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS).
Depletion of RDGB or its mis-localization away from the ER-PM MCS results in
multiple defects in photoreceptor function. Previously, the interaction between
the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be
essential for accurate localization to ER-PM MCS. Here, we report that the
FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this
also requires the function of the C-terminal domains, DDHD and LNS2. Mutations
in each of these domains results in mis-localization of RDGB leading to loss of
function. While the LNS2 domain is necessary, it is not sufficient for the
correct localization of RDGB, which also requires the C-terminal DDHD domain.
The function of the DDHD domain is mediated through an intramolecular
interaction with the LNS2 domain. Thus, interactions between the additional
domains in a multi-domain PITP together lead to accurate localization at the MCS
and signalling function.
Mechanisms of punctuated vision in fly flight
Authors: Cellini Benjamin , Salem Wael , Mongeau Jean-Michel
Published: December 2021

To guide locomotion, animals control their gaze via movements of their eyes, head, and/or body, but how the nervous system controls gaze during complex motor tasks remains elusive. Notably, eye movements are constrained by anatomical limits, which requires resetting eye position. By studying tethered, flying flies (Drosophila) in a virtual reality flight simulator, we show that ballistic head movements (saccades) reset eye position, are stereotyped and leverage elastic recoil of the neck joint, enabling mechanically assisted redirection of gaze. Head reset saccades were of proprioceptive origin and interrupted smooth movements for as little as 50 ms, enabling punctuated, near-continuous gaze stabilization. Wing saccades were modulated by head orientation, establishing a causal link between neck signals and execution of body saccades. Furthermore, we demonstrate that head movements are gated by behavioral state. We propose a control architecture for biological and bio-inspired active vision systems with limits in sensor range of motion.
Exposure to relaxing words during sleep promotes slow-wave sleep and subjective sleep quality
Authors: Beck Jonas , Loretz Erna , Rasch Björn
Published: December 2021

Our thoughts alter our sleep, but the underlying mechanisms are still unknown. We propose that mental processes are active to a greater or lesser extent during sleep and that this degree of activation affects our sleep depth. We examined this notion by activating the concept of “relaxation” during sleep using relaxation-related words in 50 healthy participants. In support of our hypothesis, playing relaxing words during non-rapid eye movement sleep extended the time spent in slow-wave sleep, increased power in the slow-wave activity band after the word cue, and abolished an asymmetrical sleep depth during the word presentation period. On the subjective level, participants reported a higher sleep quality and elevated alertness ratings. Our results support the notion that the activation of mental concepts during sleep can influence sleep depth and provide a basis for interventions using targeted activations to promote sleep depth and sleep quality to foster well-being and health.
Social status and previous experience in the group as predictors of long-term welfare of sows housed in large semi-static groups
Authors: Brajon Sophie , Ahloy-Dallaire Jamie , Devillers Nicolas , Guay Frédéric
Published: December 2021

Mixing gestating sows implies hierarchy formation and has detrimental consequences on welfare. The effects of social stress on the most vulnerable individuals may be underestimated and it is therefore important to evaluate welfare between individuals within groups. This study aimed at investigating the impact of social status and previous experience in the group on well-being of sows housed in large semi-static groups (20 groups of 46-91 animals). We assessed aggression (d0 (mixing), d2, d27, d29), body lesions (d1, d26, d84) and feeding order. Social status was based on the proportion of fights won during a 6-hr observation period between d0 and d2. Dominants (29%) were those who won more fights than they lost, Subdominants (25%) won fewer fights than they lost, Losers (23%) never won any fight in which they were involved while Avoiders (23%) were never involved in fights. Resident sows (70%) were already present in the group in the previous gestation while New sows (30%) were newly introduced at mixing. Subdominants and Dominants were highly involved in fights around mixing but this was more detrimental for Subdominants than Dominants, Losers and Avoiders since they had the highest body lesion scores at mixing. Avoiders received less non-reciprocal agonistic acts than Losers on d2 (P=0.0001) and had the lowest body lesion scores after mixing. However, Avoiders and Losers were more at risk in the long-term since they had the highest body lesions scores at d26 and d84. They were followed by Subdominants and then Dominants. New sows fought more (P<0.0001), tended to be involved in longer fights (P=0.075) around mixing and had more body lesions throughout gestation than Resident sows. Feeding order from one-month post-mixing was influenced both by the previous experience in the group and social status (P<0.0001). New sows, especially with a low social status, are more vulnerable throughout gestation and could serve as indicators of non-optimal conditions.
The contribution of leaf sulfur content to the leaf economics spectrum explained by plant adaptive strategies
Authors: Fratte Michele Dalle , Pierce Simon , Zanzottera Magda , Leone Cerabolini Bruno Enrico
Published: December 2021

Sulfur is an essential macronutrient for plant metabolism. Terrestrial ecosystems have faced extensive anthropogenic sulfur depositions during the 20thcentury, but currently decreasing trend of sulfur emissions suggest that it could become limiting, although its relationship with plant economics remains unclear.

We analysed leaf and nutrient traits for 740 vascular plant species growing in a wide range of environmental conditions. We aimed to determine whether leaf sulfur content (LSC) is associated with the leaf economics spectrum, and whether its distribution among functional types (life forms, leaf life span categories, and Grime’s CSR (Competitive, Stress-tolerant, Ruderal) strategies) could help to elucidate adaptive differences within plant taxa.

High LSC values corresponded mainly with R-, and to a lesser extent C-, strategy selection, hence the acquisitive extreme of plant economics. We found evidence of a relationship between nutrient stoichiometry and taxonomy, specifically at the acquisitive and conservative extremes of leaf economics. In general, LSC was significantly and positively correlated with leaf nitrogen content, but ruderal strategies in particular exhibited greater sulfur to nitrogen ratios.

Faced with a dearth of LSC data, leaf nitrogen content could thus be used as a coarse proxy of LSC within the context of plant economics. Different ratios among sulfur and nitrogen may be expected for ruderal species, suggesting that deeper insights from CSR strategies can provide a bridge between plant stoichiometry and ecology.
Machine learning approach to dynamic risk modeling of mortality in COVID-19: a UK Biobank study
Authors: Dabbah Mohammad A. , Reed Angus B. , Booth Adam T.C. , Yassaee Arrash , Despotovic Alex , Klasmer Benjamin , Binning Emily , Aral Mert , Plans David , Labrique Alain B. , Mohan Diwakar
Published: December 2021

The COVID-19 pandemic has created an urgent need for robust, scalable monitoring tools supporting stratification of high-risk patients. This research aims to develop and validate prediction models, using the UK Biobank, to estimate COVID-19 mortality risk in confirmed cases. From the 11,245 participants testing positive for COVID-19, we develop a data-driven random forest classification model with excellent performance (AUC: 0.91), using baseline characteristics, pre-existing conditions, symptoms, and vital signs, such that the score could dynamically assess mortality risk with disease deterioration. We also identify several significant novel predictors of COVID-19 mortality with equivalent or greater predictive value than established high-risk comorbidities, such as detailed anthropometrics and prior acute kidney failure, urinary tract infection, and pneumonias. The model design and feature selection enables utility in outpatient settings. Possible applications include supporting individual-level risk profiling and monitoring disease progression across patients with COVID-19 at-scale, especially in hospital-at-home settings.
Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals
Authors: Sano Kaori , Bhavsar Disha , Singh Gagandeep , Floda Daniel , Srivastava Komal , Gleason Charles ,   PARIS Study Group, Carreño Juan Manuel , Simon Viviana , Krammer Florian
Published: December 2021

Mucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.
Effects of midfoot joint mobilization on perceived ankle-foot function in chronic ankle instability. A crossover clinical trial
Authors: Jaffri Abbis , Fraser John J. , Koldenhoven Rachel M. , Hertel Jay
Published: December 2021

Background

Chronic ankle instability (CAI) is a complex clinical entity that commonly includes ankle-foot impairment.

Objective

To investigate the effects of midfoot joint mobilizations and a one-week home exercise program (HEP) compared to a sham intervention and HEP on pain, patient-reported outcomes (PROs), ankle-foot joint mobility, and neuromotor function in young adults with CAI.

Methods

Twenty participants with CAI were instructed in a stretching, strengthening, and balance HEP and were randomized a priori to receive midfoot joint mobilizations (forefoot supination, cuboid glide and plantar 1st tarsometatarsal) or a sham laying-of-hands. Changes in foot morphology, joint mobility, strength, dynamic balance, and PROs assessing pain, physical, and psychological function were assessed pre-to-post treatment and one-week following. Participants crossed-over to receive the alternate treatment and were assessed pre-to-post treatment and one-week following. Linear modelling was used to assess changes in outcomes.

Results

Participants who received midfoot mobilization demonstrated significantly greater perceived improvement immediately posttreatment in the single assessment numeric evaluation (Sham: 5.0±10.2%; Mobilization: 43.9±26.2%; β: 6.8 p<0.001, Adj R2:0.17) and Global Rating of Change (Sham: −0.1±1.1; Mobilization: 1.1±3.0; β: 1.8 p=0.01, Adj R2:0.12). Following the mobilization intervention, participants demonstrated greater improved rearfoot inversion mobility (Sham: 4.4±8.4°; Mobilization: −1.6±6.1°; β: −6.37, p=0.01, Adj R2:0.19), plantarflexion mobility (Sham: 2.7°±6.4; Mobilization: −1.7°±4.3; β: −4.36, p=0.02, Adj R2:0.07), and posteromedial dynamic balance (Sham: 2.4±5.9%; Mobilization: 6.0±5.4%; β: 3.88, p=0.04, Adj R2:0.10) compared to controls at 1-week post-treatment.

Conclusion

Participants with CAI who received midfoot joint mobilization had greater perceived improvement and physical signs that may benefit this clinical population.
Aerosol emission rates from playing wind instruments – Implications for COVID-19 transmission during music performance
Authors: Firle C. , Steinmetz A. , Stier O. , Stengel D. , Ekkernkamp A.
Published: December 2021

Background

The pandemic of COVID-19 led to exceeding restrictions especially in public life and music business. Airborne transmission of SARS-CoV-2 demands for risk assessment also in wind playing situations. Previous studies focused on short-range transmission, whereas long-range transmission has not been assessed so far.

Methods and findings

We measured resulting aerosol concentrations in a hermetically closed cabin of 20 m3in an operating theatre from 20 minutes standardized wind instrument playing (19 flute, 11 oboe, 1 clarinet, 1 trumpet players). Based on the data, we calculated total aerosol emission rates showing uniform distribution for both instrument groups (flute, oboe). Aerosol emission from wind instruments playing ranged from 7 ± 327 particles/second (P/s) up to 2583 ± 236 P/s, average rate ± standard deviation. The analysis of the aerosol particle size distribution showed that about 70 − 80% of emitted particles had a size ≤ 0.4 µm and thus being alveolar. Masking the bell with a surgical mask did not reduce aerosol emission. Aerosol emission rates were higher from wind instruments playing than from speaking and breathing. Differences between instrumental groups could not be found, but high interindividual variance as expressed by uniform distribution of aerosol emission rates.

Conclusions

Our findings indicate that aerosol emission depends on physiological factors and playing techniques rather than on the type of instrument, in contrast to some previous studies. Based on our results, we present risk calculations for long-range transmission of COVID-19 for three typical woodwind playing situations.
A standardized approach for case selection and genomic data analysis of maternal exomes for the diagnosis of oocyte maturation and early embryonic developmental arrest in IVF
Authors: Capalbo A. , Buonaiuto S. , Figliuzzi M. , Damaggio G. , Girardi L. , Caroselli S. , Poli M. , Patassini C. , Cetinkaya M. , Yuksel B. , Azad A. , Grøndahl M. L. , Hoffmann E. R. , Simón C. , Colonna V. , Kahraman S.
Published: December 2021

OBJECTIVE

To develop a methodology for case selection and whole-exome sequencing (WES) analysis in infertile women due to recurrent oocyte maturation defects(OOMD) and/or preimplantation embryo lethality (PREMBL).

DESIGN

Retrospective cohort study.

SETTING

IVF patients attending the Istanbul Memorial Hospital (2015-2021). WES and bioinformatics were performed at Igenomix and National Research Council, Italy.

PATIENTS

A statistical methodology for identification of infertile endophenotypes (recurrent low oocyte maturation rate, LMR, low fertilization rate, LFR, and preimplantation developmental arrest, PDA, was developed using a large IVF dataset (11,221 couples). 28 OOMD/PREMBL infertile women were subsequently enrolled for WES.

INTERVENTION

30X-WES was performed on women’s gDNA. Pathogenic variants were prioritized using a custom-made bioinformatic pipeline set to minimize false positive discoveries through resampling in control cohorts (i.e., HGDP and 1,343 WES from oocyte donors). Individual scRNAseq data from 18 human MII oocytes and antral granulosa cells(AGC) was used for genome-wide validation.

MAIN OUTCOME MEASURE

Identification of High-impact variants causative of OOMD/PREMBL endophenotypes.

RESULTS

Variant prioritization analysis identified 265 unique variants in 248 genes (average per sample 22.4). 87.8% of genes harbouring high-impact variants are expressed by MII oocytes and/or AGC, significantly higher compared to a random sample of controls. Seven of the 28 women (25%) are homozygous carriers of missense pathogenic variants in known candidate genes for OOMD/PREMBL, including PATL2, NLRP5 (N=2), TLE6,PADI6, TUBB8 and TRIP13. Furthermore, novel gene-disease associations were identified. One LMR woman was a homozygous carrier of high impact variants in ELSA, an essential gene for phopase I meiotic transition in mice, whereas three women carried biallelic pathogenic variants in CEP128 gene, participating in the formation of the spindle in mitosis and ciliogenesis.

CONCLUSIONS

This analytical framework revealed known and new genes associated with isolated recurrent OOMD/PREMBL, providing essential indications for scaling this strategy to larger studies.
Delta Variant SARS-CoV-2 infections in pediatric cases during the second wave in India
Authors: Yadav Pragya D. , Kumar Gunjan , Mukherjee Aparna , Nyayanit Dimpal A. , Shete Anita M. , Sahay Rima R. , Kumar Abhinendra , Majumdar Triparna , Patil Savita , Pandit Priyanka , Joshi Yash , Dudhmal Manisha , Panda Samiran , Sharma Lokesh Kumar , Kala Yadav ML , Shastri Jayanthi , Gangwar Mayank , Munivenkattapa Ashok , Potdar Varsha , Nagamani K , Goyal Kapil , Gadepalli Ravisekhar , Thomas Maria , Shukla Suruchi , Nagraj P , Gupta Vivek , Dalela Gaurav , Umar Nawaz , Patel Sweety M
Published: December 2021

The aim of this study was to identify the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n=583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021.Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.
Nipah virus outbreak in Kerala state, India amidst of COVID-19 pandemic
Authors: Yadav Pragya D. , Sahay Rima R. , Anukumar B , Mohandas Sreelekshmy , Radhakrishnan Chandni , Gokhale Mangesh D , Balasubramaniam R , Abraham Priya , Gupta Nivedita , Sugunan AP , Khobragade Rajan , George Kalpana , Shete Anita , Patil Savita , Thankappan Ullas Padinjaremattathil , Dighe Hitesh , Koshy Jijo , Vijay Vivek , Gayathri R , Kumar P Jayesh , Rahim Asma , Naveen A. , Nair Sarala , Rajendran VR , Jayasree V , Majumdar Triparna , Jain Rajlaxmi , Vishwanathan Prasanth , Patil Deepak Y. , Kumar Abhinendra , Nyayanit Dimpal A. , Sarkale Prasad , Waghmare Ashwini , Baradkar Shrikant , Gawande Pranita , Bodake Poonam , Kalele Kaumudi , Yemul Jyoti , Dhaigude Sachin , Holepannawar Manjunath , Gopale Sanjay , Chopade Ganesh , Narayan Jitendra , Mathapati Basavaraj , Kadam Manoj , Kumar Abhimanyu , Suryawanshi Annasaheb , Jose Beena Philomina , Sivadas Saritha , Akash NP , Vimisha TV , Keerthi KV
Published: December 2021

Background

We report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India which had caused fatal encephalitis in an adolescent male and the outbreak response which led to the successful containment of the disease and the related investigations.

Methods

Quantitative real-time RT-PCR, ELISA based antibody detection and whole genome sequencing were performed to confirm the Nipah virus infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs and blood samples for Nipah virus screening by real time RT-PCR and anti-Nipah virus bat IgG ELISA. Plaque reduction neutralization test was performed for the detection of neutralizing antibodies.

Results

Nipah viral RNA and anti-NiV IgG antibodies were detected in the serum of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius and 37.73% of Rousettus leschenaultia. Neutralizing antibodies against NiV could be detected in P.medius.

Conclusions

Stringent surveillance and awareness campaigns needs to be implemented in the area to reduce human-bat interactions and minimize spill over events which can lead to sporadic outbreaks of NiV.
Prognostic association supports indexing size measures in echocardiography by body surface area
Authors: Fung Angus SY , Soundappan Dhnanjay , Loewenstein Daniel E , Playford David , Strange Geoffrey , Kozor Rebecca , Otton James , Ugander Martin
Published: December 2021

BACKGROUND

BSA is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (BMI<18.5 kg/m2or ≥30 kg/m2, respectively).

AIMS

We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than body surface area (BSA) regardless of body mass index (BMI).

METHODS

Adult patients with no prior valve replacement were selected from the National Echocardiography Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint.

RESULTS

Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n=230,109] and mass [n=224,244], left atrial area [n=90,596], aortic sinus diameter [n=90,805], right atrial area [n=59,516], right ventricular diameter [n=3,278], right ventricular outflow tract diameter [n=1,406]) by BSA had better prognostic performance vs unindexed measures (normal weight/overweight: average C-statistic 0.661 vs 0.620; underweight: C-statistic 0.650 vs 0.648; obese: C-statistic 0.627 vs 0.614). Indexation by other body size metrics (lean body mass, height, and/or weight raised to different powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤0.02), with smaller differences in other BMI subgroups.

CONCLUSIONS

Indexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.