bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steep repolarization time gradients in pig hearts cause distinct changes in composite electrocardiographic T‐wave parameters
Authors: van der Waal Jeanne , Bear Laura , Meijborg Veronique , Dubois Rémi , Cluitmans Matthijs , Coronel Ruben 
Published: August 2022

AbstractBackgroundThe T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T‐wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T‐wave markers to controlled drug‐induced regional RT gradients in intact pig hearts.MethodsRepolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff‐perfused hearts placed inside a torso tank. From the 12‐lead ECG on the torso tank, the mean, maximum, and dispersion (max–min) of QTtime, JTtime, Tpeak–end, Twidth, TQratio, dV/dtmax, Tarea, Tamp, and T‐upslope duration were determined, as well as upslope end difference between leads V1 and V6.ResultsTemporal T‐wave parameters Tpeak–end, Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T‐upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1–V6 upslope end difference were not significantly correlated with RT gradient.ConclusionComposite 12‐lead ECG T‐wave parameters Tpeak–end, Twidth, TQratio, upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T‐wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.
The role of extracorporeal membrane oxygenation in adult kidney transplant patients: A qualitative systematic review of literature
Authors: Reid Trista D. , Kratzke Ian , Dayal Diana , Raff Lauren , Serrano Pablo , Kumar Aman , Boddie Olivia , Zendel Alex , Gallaher Jared , Carlson Rebecca , Boone Joshua , Charles Anthony G. , Desai Chirag S. 
Published: August 2022

AbstractBackgroundA paucity of evidence exists regarding the risks and benefits of Extracorporeal Membrane Oxygenation (ECMO) in adult kidney transplantation.MethodsThis was a systematic review conducted from Jan 1, 2000 to April 24, 2020 of adult kidney transplant recipients (pre‐ or post‐ transplant) and donors who underwent veno‐arterial or veno‐venous ECMO cannulation. Death and graft function were the primary outcomes, with complications as secondary outcomes.ResultsTwenty‐three articles were identified that fit inclusion criteria. 461 donors were placed on ECMO, with an overall recipient 12‐month mortality rate of 1.3% and a complication rate of 61.5%, the majority of which was delayed graft function. Fourteen recipients were placed on ECMO intraoperatively or postoperatively, with infection as the most common indication for ECMO. The 90‐day mortality rate for recipients on ECMO was 42.9%, with multisystem organ failure and infection as the ubiquitous causes of death. 35.7% of patients experienced rejection within 6 months of decannulation, yet all were successfully treated.ConclusionsECMO use in adult kidney transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO mirrors that of recipients from standard criteria donors. The morbidity and mortality of recipients placed on ECMO are also similar to other patient populations requiring ECMO.
Social connectedness, emotional regulation, and health behaviors as correlates of distress during lockdown for COVID‐19: A diary study
Authors: Muñoz‐Martínez Amanda M. , Naismith Iona 
Published: August 2022

AbstractMass lockdowns are a powerful infection‐reduction strategy but are a significant stressor. This study aimed to explore whether various factors known to predict distress in normal contexts (e.g. social connectedness, emotional‐regulation strategies, and health‐related behaviors) are associated with daily distress under lockdown conditions. A time‐based diary study evaluated how perceived social connectedness, health‐promoting, and risk behaviors predicted within‐person and between‐person psychological distress. One hundred and nine adults completed surveys on these variables daily for 15 days while under stringent COVID‐19 lockdown in Colombia. Emotional suppression and reappraisal were measured at the start of the study to explore whether they predicted distress. Distress was lower on the days that people experienced greater social connectedness (within‐person analyses) but was not significantly predicted by between‐participant differences in emotional regulation. Health‐promoting behaviors such as exercising and meaningful activity were associated with lower distress, while watching COVID‐19 news and eating high‐calorie food were associated with higher distress. Looking at individual dynamics provides meaningful insights on daily behaviors associated with distress that might improve people's wellbeing during lockdown, such as social connectedness, meaningful activity, nutrition, exercise, and minimizing news exposure. Future research with alternative designs will enable causal conclusions to be drawn.
Integrated morphometric and molecular analyses indicate three male morphotypes in the freshwater prawn Macrobrachium olfersii (Decapoda, Palaemonidae) along the Brazilian neotropical region
Authors: Rossi Natália , Pantaleão João Alberto Farinelli , Mantelatto Fernando L. 
Published: August 2022

AbstractMales of Macrobrachium olfersii have a large cheliped (second pereiopod) with individual variations in shape and ornamentation, and they vary in size within and between populations. Some misidentification or doubts about taxonomic validity occur due to this morphological variability throughout their geographic distribution. We carried out a morphometric analysis to detect specific patterns and the potential occurrence of morphotypes in M. olfersii from different populations. Our data set included 52 females and 109 males collected in the Neotropical region, between the north and south limits of Brazilian territory, in coastal rivers from the states of Rio Grande do Norte, Bahia, Espírito Santo, Rio de Janeiro, São Paulo, Paraná and Santa Catarina. Body measurements were size standardized by allometric methods and explored by the principal component analysis (PCA) and non‐hierarchical analysis of K‐means clustering and canonical variate analysis (CVA). Our results suggested three distinct morphological groups (morphotypes) only for males in M. olfersii. Furthermore, the confirmation of monophyly of the different populations of M. olfersii was accomplished by sequences of 16S rDNA. Additional studies about relative growth in other populations and the analysis of the entire ontogenetic development of males in the laboratory will be important to complement the knowledge about morphotypes in this species.
Hospital pharmacists' opinions on a risk prediction tool for medication‐related harm in older people
Authors: Hussain Ahmed , Ali Khalid , Davies J. Graham , Stevenson Jennifer M. , Lippett Samantha , O'Malley Mairead , Parekh Nikesh , Rajkumar Chakravarthi 
Published: August 2022

AimOlder adults are particularly affected by medication‐related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk‐prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME‐RPT.MethodsTen hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case‐vignettes each with a calculated PRIME‐RPT score to help guide discussion. Case‐vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a “framework” approach.ResultsSeven themes emerged in relation to the PRIME‐RPT: (1) providing a medicine‐prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow‐up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations.ConclusionHospital pharmacists found the PRIME‐RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.
Preclinical efficacy in investigator's brochures: Stakeholders' views on measures to improve completeness and robustness
Authors: Haslberger Martin , Schorr Susanne Gabriele , Strech Daniel , Haven Tamarinde 
Published: August 2022

AimsResearch ethics committees and regulatory agencies assess whether the benefits of a proposed early‐stage clinical trial outweigh the risks based on preclinical studies reported in investigator's brochures (IBs). Recent studies have indicated that the reporting of preclinical evidence presented in IBs does not enable proper risk‐benefit assessment. We interviewed different stakeholders (regulators, research ethics committee members, preclinical and clinical researchers, ethicists, and metaresearchers) about their views on measures to increase the completeness and robustness of preclinical evidence reporting in IBs.MethodsThis study was preregistered (https://osf.io/nvzwy/). We used purposive sampling and invited stakeholders to participate in an online semistructured interview between March and June 2021. Themes were derived using inductive content analysis. We used a strengths, weaknesses, opportunities and threats matrix to categorize our findings.ResultsTwenty‐seven international stakeholders participated. The interviewees pointed to several strengths and opportunities to improve completeness and robustness, mainly more transparent and systematic justifications for the included studies. However, weaknesses and threats were mentioned that could undermine efforts to enable a more thorough assessment: The interviewees stressed that current review practices are sufficient to ensure the safe conduct of first‐in‐human trials. They feared that changes to the IB structure or review process could overburden stakeholders and slow drug development.ConclusionIn principle, more robust decision‐making processes align with the interests of all stakeholders and with many current initiatives to increase the translatability of preclinical research and limit uninformative or ill‐justified trials early in the development process. Further research should investigate measures that could be implemented to benefit all stakeholders.
Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study
Authors: Landis Megan N. , Arya Mark , Smith Stacy , Draelos Zoe , Usdan Lisa , Tarabar Sanela , Pradhan Vivek , Aggarwal Sudeepta , Banfield Christopher , Peeva Elena , Vincent Michael S. , Sikirica Vanja , Xenakis Jason , Beebe Jean S. 
Published: August 2022

Abstract

Background
Atopic dermatitis (AD) is a prevalent inflammatory, pruritic skin disease. The Janus kinase (JAK) pathway is a treatment target.

Objectives
To assess the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2 (TYK2)/JAK1 inhibitor, in participants with mild-to-moderate AD.

Methods
In this phase IIb, double-blind, dose-ranging study, participants were randomized to receive one of eight treatments for 6 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. The primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) total score at week 6. Adverse events (AEs) were monitored.

Results
Overall, 292 participants were enrolled and randomized. The brepocitinib 1% QD and 1% BID groups achieved statistically significantly greater (with multiplicity-adjusted P &lt; 0·05 due to Hochberg’s step-up method) percentage reductions from baseline in EASI total score at week 6 [least squares mean (90% confidence interval, CI): QD: –70·1 (–82·1 to –58·0); BID: –75·0 (–83·8 to –66·2)] compared with respective vehicle [QD: –44·4 (–57·3 to –31·6); BID: –47·6 (–57·5 to –37·7)]. There was not a dose-dependent trend in AE frequency, and there were no serious AEs or deaths.

Conclusions
Topical brepocitinib is effective and well tolerated in participants with mild-to-moderate AD.
What is already known about this topic? Janus kinase (JAK) inhibitors are in development for treatment of atopic dermatitis (AD).The tyrosine kinase 2 and JAK 1 inhibition by brepocitinib may bring a new profile for topical JAK inhibitors for treatment of mild-to-moderate AD.
What does this study add? Topical brepocitinib can provide rapid, effective symptom reduction, and could offer a novel alternative to current topical treatments for mild-to-moderate AD.
Exploring the promotion of youth voice in community‐based youth development programmes
Authors: Bloomer Rebecka , Harris Lesley M. , Brown Aishia A. , Crosby Shantel 
Published: August 2022

AbstractThis constructivist grounded theory study used semi‐structured interviews with 19 youth service providers in community‐based youth development programmes to develop a context‐specific framework of how and why youth voice promotion occurred. Factors external to the youth programmes, such as funder expectations, influenced the conceptualization of role for youth workers. The social process of meaning making in relation to role identity impacted how youth workers perceived self‐efficacy when working with youth, especially when engaged with behaviours falling outside programmatic expectations or norms. Workers prioritized fostering physical and psychological safe spaces for youth participants. When conflict occurred, perceptions of efficacy guided workers in taking positions that either promoted or restricted youth voice based on their perceptions of efficacy in resolving conflict safely. Youth programmes have the capacity to resist or replicate oppression present within the educational system. The adoption and adaptation of educational models of resistance offer a strategy for community‐based youth organizations to promote equity and thriving youth.
Predicting the Structure of a Lexical Environment from Properties of Verbal Working Memory
Authors: Tanida Yuki , Saito Satoru 
Published: August 2022

AbstractWe analyzed a Japanese lexical database to investigate the structure of the lexical environment based on the hypothesis that the lexical environment is optimized for the functioning of verbal working memory. Our prediction was that, as a consequence of the cultural transmission of language, low‐imageable meanings tend to be represented by frequent phonological patterns in the current vocabulary rather than infrequent phonological patterns. This prediction was based on two findings of previous laboratory studies on verbal working memory. (1) The quality of phonological (phonemic and accent) representations in verbal working memory depends on phonological regularity knowledge; therefore, short‐term phonological representations are less robust for words with infrequent phonological patterns. (2) Phonological representations are underpinned by contributions from semantic knowledge; therefore, phonological representations of highly imageable words are more robust than those for low‐imageable words. Our database analyses show that nouns with less imageable meanings tend to be associated with more frequent phonological patterns in Japanese vocabulary. This lexical structure can maintain the quality of phonological representations in verbal working memory through contributions of semantic and phonological regularity knowledge. Larger semantic contributions compensate for the less robust phonological representations of infrequent phonological forms. The quality of phonological representations is preserved by phonological regularity knowledge when larger semantic contributions are not expected.
Cystathionine β‐synthase is required for oocyte quality by ensuring proper meiotic spindle assembly
Authors: Cao Yan , Zhu Xinyu , Zhen Panpan , Tian Ying , Ji Dengyu , Xue Ke , Yan Wenjing , Chai Jiayin , Liu Huirong , Wang Wen 
Published: August 2022

AbstractObjectivesPoor oocyte quality is detrimental to fertilization and embryo development, which causes infertility. Cystathionine β‐synthase (CBS) is one of the key enzymes modulating the metabolism of homocysteine (Hcy). Studies have shown that CBS plays an important role in female reproduction. However, the role of CBS in regulating oocyte quality during meiotic maturation still needs further investigation.Materials and MethodsImmunohistochemistry, immunofluorescence, drug treatment, western blot, cRNA construct and in vitro transcription, microinjection of morpholino oligo and cRNA were performed for this study.ResultsWe found that CBS was expressed both in human and mouse oocytes of follicles. In mouse oocytes, CBS was distributed in the nucleus at germinal vesicle (GV) stage and localized to spindle from germinal vesicle breakdown (GVBD) to metaphase II (MII). The expression of CBS was reduced in ovaries and oocytes of aged mice. CBS depletion resulted in meiotic arrest, spindle abnormality and chromosome misalignment, disrupted kinetochore‐microtubule attachments and provoked spindle assembly checkpoint (SAC). CBS was disassembled when microtubules were disrupted with nocodazole, and co‐localized with the stabilized microtubules after taxol treatment. Furthermore, CBS depletion decreased the acetylation of α‐tubulin.ConclusionsThese results reveal that CBS is required for the acetylation of α‐tubulin to ensure proper spindle assembly in regulating oocyte quality during meiotic maturation.
Senescent cells: A therapeutic target for osteoporosis
Authors: Wang Tiantian , Huang Shishu , He Chengqi 
Published: August 2022

AbstractBackgroundOsteoporosis (OP) is a prevalent disorder characterized by the loss of bone mass and the deterioration of bone microarchitecture. OP is attributed to various factors, including menopause (primary), ageing (primary) and the adverse effects of medications (secondary). Recently, cellular senescence has been shown to have a crucial role in the maintenance of cellular homeostasis and organ function. The purpose of this review is to summarize recent findings regarding the roles of bone cellular senescence and senescence‐associated secretory phenotype (SASP) in OP.MethodsA comprehensive search of the PubMed database from inception to July 2022 was performed regarding the molecular mechanism of bone cell senescence in OP progression.ResultsWe describe the pathophysiology of senescent bone cells and SASP, and how each contributes to OP. We also provide new options for treating OP by targeting cellular senescence pathways.ConclusionCellular senescence plays an important role in bone homeostasis, with variations based on the different types of OP. These variations are associated with pathogenic factors, bone turnover rate and systemic metabolism. Understanding the molecular relationship between bone cells and senescence provides for the possible targeting of senescence as a means by which to treat OP.
Genetic patterns in three South African specialist antelope species: Threats, conservation management and their implications
Authors: Phukuntsi Metlholo Andries , Dalton Desire Lee , Mwale Monica , Selier Jeanetta , Cebekhulu Thando , Sethusa Mamadi Theresa 
Published: August 2022

AbstractGenetic diversity is a fundamental measure of a populations ability to adapt to future environmental change. Subpopulations may carry unique genetic lineages that contribute to fitness and genetic diversity of species across their distribution range. Therefore, considerations, or lack thereof, of genetic diversity in wildlife management practices may result in either population persistence or extinction over time. Some management tools may pose a greater risk to a species' survival than others when populations are impacted. In South Africa, there has been great interest to translocate animals, sometimes with little consideration to the potential impacts on the species and/or populations survival. Thus, there is a need to collate scientific information to better inform decision‐making and review these management practices and their effects on populations. Here, we focus on three antelope species, the blue duiker (Philantomba monticola), oribi (Ourebia ourebi), and tsessebe (Damaliscus lunatus). We review the genetic status of each species across South Africa, with regards to taxonomy, genetic diversity and population structure, threats that may compromise the genetic diversity within species and across populations, conservation management actions and how they may compromise or benefit the genetic status and lastly make recommendations on possible alternative management actions and future research to inform conservation policy and sustainable management practice.
Alternative splicing for germ cell‐specific Mga transcript can be eliminated without compromising mouse viability or fertility
Authors: Kitamura Yuka , Suzuki Ayumu , Uranishi Kousuke , Nishimoto Masazumi , Mizuno Seiya , Takahashi Satoru , Okuda Akihiko 
Published: August 2022

AbstractThe stimulated by retinoic acid gene 8 (STRA8)/MEIOSIN complex and polycomb repressive complex (PRC) 1.6, a PRC1 subtype, are believed to be positive and negative regulators of meiotic onset, respectively. During meiotic initiation, the transcription repressive activity of PRC1.6 must be attenuated so that meiosis‐related genes can be effectively activated by the STRA8/MEIOSIN complex. However, the molecular mechanisms that control the impairment of PRC1.6 function remain unclear. We recently demonstrated that the Mga gene, which encodes a scaffolding component of PRC1.6, produces variant mRNA by alternative splicing specifically during meiosis. Furthermore, the anomalous MGA protein encoded by the variant mRNA bears an intrinsic ability to function as a dominant negative regulator against the construction of PRC1.6 and is therefore assumed to be, at least in part, involved in impairment of the complex. Therefore, to unequivocally evaluate the physiological significance of Mga variant mRNA production in gametogenesis, we examined the consequences of a genetic manipulation that renders mice unable to produce Mga variant mRNA. Our data revealed that mutant mice were equivalent to wild‐type mice in terms of viability and fertility. Our detailed examination of spermatogenesis also revealed that this genetic alteration is not associated with any apparent abnormalities in testis size, spermatogenic cycle, timing of meiotic onset, or marker gene expression of spermatogonia and spermatocytes. Taken together, these data indicate that the production of germ cell‐specific Mga variant mRNA is dispensable not only for viability but also for gametogenesis.