bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Thick Filament Activation Suggests a Molecular Basis for Force Depression
Authors: Liu Shuyue , Marang Chris , Woodward Mike , Joumaa Venus , Leonard Tim , Scott Brent , Debold Edward , Herzog Walter , Walcott Sam 
Published: September 2023

ABSTRACTMultiscale models aiming to connect muscle’s molecular and cellular function have been difficult to develop, in part, due to a lack of self-consistent multiscale data. To address this gap, we measured the force response from single skinned rabbit psoas muscle fibers to ramp shortenings and step stretches performed on the plateau region of the force-length relationship. We isolated myosin from the same muscles and, under similar conditions, performed single molecule and ensemble measurements of myosin’s ATP-dependent interaction with actin using laser trapping and in vitro motility assays. We fit the fiber data by developing a partial differential equation model that includes thick filament activation, whereby an increase in force on the thick filament pulls myosin out of an inhibited state. The model also includes a series elastic element and a parallel elastic element. This parallel elastic element models a titin-actin interaction proposed to account for the increase in isometric force following stretch (residual force enhancement). By optimizing the model fit to a subset of our fiber measurements, we specified seven unknown parameters. The model then successfully predicted the remainder of our fiber measurements and also our molecular measurements from the laser trap and in vitro motility. The success of the model suggests that our multiscale data are self-consistent and can serve as a testbed for other multiscale models. Moreover, the model captures the decrease in isometric force observed in our muscle fibers after active shortening (force depression), suggesting a molecular mechanism for force depression, whereby a parallel elastic element combines with thick filament activation to decrease the number of cycling cross-bridges.SIGNIFICANCEConnecting the molecular and cellular scales of muscle contraction would assist in, e.g., the treatment of genetic muscle diseases, the development of heart drugs, and the design of prostheses. The history dependence of muscle contraction, having no clear molecular basis, has remained an obstacle in making this connection for the seventy years since its discovery. We measured the force- and motion-generating capacity of rabbit psoas muscle from the scale of single molecules to single cells. We developed a mathematical model that, when fit to some of the cellular measurements, predicted the remaining cellular measurements and also the molecular measurements. The model’s ability to capture muscle’s history dependence suggests a unified description of muscle contraction from the molecular to cellular scale.
Usage of Mineralocorticoids and Isotonic Crystalloids in Subarachnoid Hemorrhage Patients in the United States
Authors: Mistry Akshitkumar M. , Naidugari Janki , Craven Jocelyn , Williams Logan , Beall Jonathan , Khatri Pooja , Broderick Joseph P. , Rice Todd W. , Kamel Hooman , Mack William 
Published: September 2023

ABSTRACTBackgroundThe usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown.MethodsWe surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20% of all acute inpatient care in the United States.ResultsAlthough mineralocorticoids are used by 70% of the NINDS StrokeNet sites in aSAH patients, it is used in less than 25% of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41% and 45%, respectively.ConclusionsThe use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving outcomes for aSAH patients must be rigorously tested in randomized clinical trials.
The Role of ACT Score in Mepolizumab Discontinuation
Authors: Solanki Neha , Beck Brittany , Labadia Monica , Smith Kevin , Peterson Laura , King Stephanie , Micklewright Sarah , Pennington Emily , Farooq Sobia , Zhang Peng , Aronica Mark , Zein Joe , Khatri Sumita , Comhair Suzy , Erzurum Serpil 
Published: September 2023

AbstractBackgroundMepolizumab is a therapy for severe asthma. However, studies on mepolizumab with external validity and diverse population from the US are lacking. There is little knowledge of the characteristics of people that discontinue mepolizumab in clinical care.ObjectiveTo investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that there are characteristics that distinguish which patients would remain on mepolizumab and which patients would discontinue the medication.MethodsBetween 2016 and 2022, patients who started on mepolizumab consented to be assessed over 18 months. At baseline, a questionnaire including demographic and medical history was collected. Laboratory findings such as ACT score, FENO (Fractional Excretion of Nitric Oxide), and spirometry were recorded. At the conclusion of the observation period, the participants were divided into two categories: Group A and Group B.ResultsGroup B [N=28] discontinued mepolizumab (P< 0.05) at an average of 5.8 months (SD 4.2 months). Group A [N=129] stayed on the therapy for at least 1 year. A participant with an ACT score less than 13 has an odds ratio of 6.64 (95% CI, 2.1 – 26.0) of discontinuing mepolizumab therapy. For a male, the odds of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1 – 11.2).ConclusionIn this real-world study, we find that high eosinophil count may not be adequate in screening which individuals will benefit from mepolizumab. Up to 17% of patients fail therapy within 6 months, with male sex and low ACT score increasing risk of mepolizumab discontinuation at Cleveland Clinic.
Efficient inhibition of fusion inhibitor HY3000 peptide to SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants
Authors: Wu Lili , Zheng Anqi , Tang Yangming , Wang Xiaoyun , Gao Yue , Lei Wenwen , Wu Guizhen , Wang Qihui , Gao George Fu 
Published: September 2023

AbstractSARS-CoV-2 continues to evolve and spread. Recently, the Omicron EG.5 lineage, bearing an additional F456L mutation in spike (S) protein compared to its ancestor XBB.1.9.2, and its sub-variant EG.5.1, which carries a further Q52H mutation, have raised concerns due to their increased prevalence and extended immune escape properties. Additionally, an alarming variant, BA.2.86, has also garnered global concern because it contains over 30 amino acid mutations in its S protein compared to BA.2, including more than 10 changes in receptor-binding domain (RBD), reminiscent of the appearance of the Omicron variant in late 2021. Therefore, there is an urgent need to assess the effectiveness of current vaccines and therapeutics against EG.5, EG.5.1 and BA.2.86. In our previous work, we reported the design and broad-spectrum antiviral activity of a peptide fusion inhibitor HY3000 against SARS-CoV-2 and its variants including XBB.1.5. Here, we continued to evaluate the inhibitory potency of the HY3000 peptide against the prevailing EG.5 and EG.5.1, as well as XBB.1.16, FL.1.5.1, FY.3 and BA.2.86. Our data indicated that the peptide retained its potent inhibitory activities against these variants, indicating its potential as a good virus fusion inhibitor with broad-spectrum therapeutic effect against current and future SARS-CoV-2 variants. Currently, the HY3000 has been finished in Phase II clinical trial in China and has also been approved to conduct clinical investigation by U.S. Food and Drug Administration (FDA), suggesting a good application prospect against the ongoing COVID-19.
Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination
Authors: Chambers Emma S , Cai Weigang , Vivaldi Giulia , Jolliffe David A , Perdek Natalia , Li Wenhao , Faustini Sian E , Gibbons Joseph M. , Pade Corinna , Richter Alex G. , Cousens Anna K , Martineau Adrian R 
Published: September 2023

AbstractVaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre- vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination.Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines.Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
Association between insecticide-treated bed net use and Burkitt lymphoma incidence in children in sub-Saharan Africa: a systematic review and population-level analysis
Authors: Schmit Nora , Kaur Jeevan , Aglago Elom K. 
Published: September 2023

AbstractBackgroundBurkitt lymphoma (BL) is one of the most common childhood cancers in sub-Saharan Africa and aetiologically linked to malaria. However, evidence for an effect of malaria interventions on BL is limited. The aim of this study was to investigate the potential population-level association between large-scale rollout of insecticide-treated bednets (ITNs) in sub-Saharan Africa in the 2000s and BL incidence.MethodsWe conducted a systematic review in Embase, Global Health and MEDLINE to assemble all available data on BL incidence rates in children aged 0-15 years in malaria-endemic sub-Saharan African countries between Jan 1, 1990 and Feb 27, 2023. We calculated pooled estimates of BL incidence in sub-Saharan Africa for the time periods before and after ITN introduction. We used model estimates of sub-national ITN use to assess the association between average population ITN use and childhood BL incidence rates in a negative binomial regression model.ResultsWe included 23 studies comprising 66 datapoints on BL incidence based on 5,226 cancer cases from locations with large-scale ITN use in 17 countries. BL rates were 44% (95% CI 12-64%) lower in the time period after ITN introduction compared to before. The pooled incidence rate of BL was 1.36 (95% CI 0.88-2.10) and 0.76 (95% CI 0.50-1.16) per 100,000 person-years before and after introduction of ITNs, respectively. After adjusting for potential confounders, a 1% increase in average ITN use in the population in the 10 years before BL data collection was associated with a 2% (95% CI 1-4%) reduction in BL incidence.ConclusionThese findings suggest that large-scale rollout of ITNs in the 2000s was associated with a reduction in childhood BL burden in sub-Saharan Africa. Although published data may not be representative of all incidence rates across sub-Saharan Africa, our study highlights a potential additional benefit of malaria control programmes.
The relationship of artificial intelligence (AI) with fake news detection (FND): a systematic literature review
Authors: Iqbal Abid , Shahzad Khurram , Khan Shakeel Ahmad , Chaudhry Muhammad Shahzad 
Published: September 2023

Purpose
The purpose of this study is to identify the relationship between artificial intelligence (AI) and fake news detection. It also intended to explore the negative effects of fake news on society and to find out trending techniques for fake news detection.

Design/methodology/approach
“Preferred Reporting Items for the Systematic Review and Meta-Analysis” were applied as a research methodology for conducting the study. Twenty-five peer-reviewed, most relevant core studies were included to carry out a systematic literature review.

Findings
Findings illustrated that AI has a strong positive relationship with the detection of fake news. The study displayed that fake news caused emotional problems, threats to important institutions of the state and a bad impact on culture. Results of the study also revealed that big data analytics, fact-checking websites, automatic detection tools and digital literacy proved fruitful in identifying fake news.

Originality/value
The study offers theoretical implications for the researchers to further explore the area of AI in relation to fake news detection. It also provides managerial implications for educationists, IT experts and policymakers. This study is an important benchmark to control the generation and dissemination of fake news on social media platforms.
Cultivating a culture of inquiry: exploring the factors influencing the integration of research and teaching in higher education institutions
Authors: Devesh Sonal , Nanjundaswamy Abhishek 
Published: September 2023

PurposeTo determine the factors influencing the perception of undergraduate students toward research–teaching nexus and also to examine its impact on the attitude of the students.Design/methodology/approachThe study used a quantitative design to examine the perceptions of students in higher education institutions in India. Descriptive and inferential statistics were used to describe the data and test the hypothesis. The data was collected using a structured questionnaire for a sample of 188 students from higher education institutions (HEIs). Further, in line with the purpose of the study and to test the hypotheses, the study used descriptive statistics, exploratory factor analysis and multivariate regression analysis.FindingsThe study demonstrates that the factors influencing the perception of undergraduate students toward research teaching nexus were identified using principal component analysis (PCA) with varimax rotation, conducted on 27 measurement items. In addition, the results of the multivariate regression analysis indicated that research-based, research-tutored and research motivation dimensions, significantly impact the graduate students' perception of research–teaching nexus.Practical implicationsThe outcomes of this research may become valid input to HEI regulators, researchers and teachers while framing the policies and implementation of the same about the pertinent issues discussed in the paper. Further, it contributes to the existing theory that teaching–research quality and level of motivation are also the predominant factors influencing the teaching–research nexus among students. In addition, the outcome of this paper also supports HEIs to achieve the United Nations Sustainable Development Goals (UNSDGs) at large.Originality/valueThis study contributes to the ongoing debate and scarce literature on research–teaching nexus at the higher education level. The factors derived in this paper propose a framework for aligning teaching and research in academic programs to create high-quality human resource in the nation.
Evolution of laparoscopic pancreaticoduodenectomy at Westmead Hospital
Authors: Chen Ji , Pham Helen , Li Crystal , Nahm Christopher B. , Johnston Emma , Hollands Michael John , Pang Tony , Pleass Henry , Lam Vincent , Richardson Arthur , Yuen Lawrence 
Published: September 2023

AbstractBackgroundDespite its proposed benefits, laparoscopic pancreaticoduodenectomy (LPD) has not been widely adopted due to its technical complexity and steep learning curve. The aim of this study was to report a single surgeon's experience in the stepwise implementation of LPD and evolution of technique over a nine‐year period in a moderate‐high volume unit.MethodsCarefully selected patients underwent LPD initially by hybrid approach (laparoscopic resection and open reconstruction), which evolved into a total LPD (laparoscopic resection and reconstruction). Data was prospectively collected to include patient characteristics, intraoperative data, evolution of technique and postoperative outcomes.ResultsA total of 25 patients underwent hybrid LPD (HLPD) and 20 patients underwent total LPD (TLPD). There was no 90‐day mortality. Three patients developed a postoperative pancreatic fistula (POPF), all of which occurred in patients undergoing HLPD. There was no POPF in 20 consecutive TLPD. There was no evidence of anastomotic strictures in the hepaticojejunostomy in patients undergoing TLPD at long term follow up.ConclusionA gradual and cautious progression from HLPD to TLPD is essential to ensure safe implementation into a unit. LPD should only be considered in carefully selected patients, with outcomes subjected to regular and rigorous independent audit.
Efficacy and safety of esketamine nasal spray in addition to standard of care in patients with major depressive disorder who have active suicidal ideation with intent: A subgroup analysis of the Asian cohort of ASPIRE I (a randomized, double‐blind, placebo‐controlled study)
Authors: Hong Jin Pyo , Malek Akramul Zikri Abd , Li Cheng‐Ta , Paik Jong‐Woo , Sulaiman Ahmad Hatim , Madriaga Gilbert , Zhuo Jianmin , Siggins Sarah , Fu Dong‐Jing , Ju Po‐Chung 
Published: September 2023

AbstractThis post‐hoc analysis evaluated the efficacy and safety of intranasal esketamine in the Asian subgroup from ASPIRE I. Patients with major depressive disorder and suicidal ideation with intent received intranasal esketamine (n = 26) or placebo (n = 27), plus standard of care for 25 days. The primary endpoint was the change in Montgomery‐Åsberg Depression Rating Scale (MADRS) total score from baseline to Day 2. The MADRS score improved in favor of esketamine (least squares mean difference: −3.8). No unexpected safety concerns were noted. The Asian subgroup showed a similar efficacy and safety profile as the total ASPIRE I cohort.
An Alternative View of Sri Lanka's Debt Crisis
Authors: Nicholas Howard , Nicholas Bram 
Published: September 2023

ABSTRACTThis article questions the validity of widely promulgated claims that Sri Lanka's debt crisis is the result of a combination of Chinese debt diplomacy and economic mismanagement in the form of fiscal and monetary excesses. The authors argue that if Sri Lanka has fallen into any kind of debt trap, it is an international sovereign bond debt trap. They further argue that the fundamental cause of the country's debt crisis is the failure of successive Sri Lankan administrations to transition towards an export‐oriented manufacturing economy focused on producing increasingly technologically sophisticated manufactured products, and lay the blame for this failure on a combination of external and domestic forces operating in tandem with one another. Since the remedial action taken by the Sri Lankan government in the context of an extended fund facility arrangement with the International Monetary Fund is premised on the contention that the source of the crisis is the protracted fiscal and monetary excesses of successive Sri Lankan administrations, this action is unlikely to offer a permanent solution to Sri Lanka's debt problem — just as similar attempts to remedy previous debt and currency crises have failed.
Beyond genocide: Towards an improved analysis and understanding of the Syrian regime's mass atrocity crimes in the Syrian Civil War
Authors: Bakkour Samer 
Published: September 2023

AbstractIn the course of the Syrian Civil War, prominent former Syrian Regime politicians, human rights observers, and foreign observers have accused the Syrian Regime of committing genocide against the country's Sunni majority. This article views these accusations as part of a wider politicization of genocide, and instead progresses beyond them to outline the case for an alternative “framing” of large‐scale atrocities committed against civilians. It accordingly proposes strategic displacement, or the deliberate large‐scale uprooting and dispersal of established communities for tactical and strategic purposes, as a preferable and more sustainable framework of engagement and analysis, and seeks to more clearly distinguish it from “ethnic cleansing” with the aim of demonstrating and underlining its unique contribution to the analysis and understanding of violent conflict. This has two benefits—first, it provides a different basis for conceptual and theoretical engagement that makes it possible to view mass atrocity as a tactical innovation in response to conflict exigencies; and second, it draws attention to internal displacement, an aspect of the conflict that has been repeatedly overlooked by international observers.
Mutations in alpha‐B‐crystallin cause autosomal dominant axonal Charcot–Marie–Tooth disease with congenital cataracts
Authors: Cortese Andrea , Currò Riccardo , Ronco Riccardo , Blake Julian , Rossor Alex M. , Bugiardini Enrico , Laurà Matilde , Warner Tom , Yousry Tarek , Poh Roy , Polke James , Rebelo Adriana , Dohrn Maike F. , Saporta Mario , Houlden Henry , Zuchner Stephan , Reilly Mary M. 
Published: September 2023

AbstractBackground and purposeMutations in the alpha‐B‐crystallin (CRYAB) gene have initially been associated with myofibrillar myopathy, dilated cardiomyopathy and cataracts. For the first time, peripheral neuropathy is reported here as a novel phenotype associated with CRYAB.MethodsWhole‐exome sequencing was performed in two unrelated families with genetically unsolved axonal Charcot–Marie–Tooth disease (CMT2), assessing clinical, neurophysiological and radiological features.ResultsThe pathogenic CRYAB variant c.358A>G;p.Arg120Gly was segregated in all affected patients from two unrelated families. The disease presented as late onset CMT2 (onset over 40 years) with distal sensory and motor impairment and congenital cataracts. Muscle involvement was probably associated in cases showing mild axial and diaphragmatic weakness. In all cases, nerve conduction studies demonstrated the presence of an axonal sensorimotor neuropathy along with chronic neurogenic changes on needle examination.DiscussionIn cases with late onset autosomal dominant CMT2 and congenital cataracts, it is recommended that CRYAB is considered for genetic testing. The identification of CRYAB mutations causing CMT2 further supports a continuous spectrum of expressivity, from myopathic to neuropathic and mixed forms, of a growing number of genes involved in protein degradation and chaperone‐assisted autophagy.