bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor β1 impairs the transcriptomic response to contraction in myotubes from women with polycystic ovary syndrome
Authors: McIlvenna Luke C. , Altıntaş Ali , Patten Rhiannon K , McAinch Andrew J. , Rodgers Raymond J. , Stepto Nigel K. , Barrès Romain , Moreno‐Asso Alba 
Published: June 2022

AbstractPolycystic ovary syndrome (PCOS) is characterised by a hormonal imbalance affecting the reproductive and metabolic health of reproductive‐aged women. Exercise is recommended as a first‐line therapy for women with PCOS to improve their overall health; however, women with PCOS are resistant to the metabolic benefits of exercise training. Here, we aimed to gain insight into the mechanisms responsible for such resistance to exercise in PCOS. We employed an in vitro approach with electrical pulse stimulation (EPS) of cultured skeletal muscle cells to explore whether myotubes from women with PCOS have an altered gene expression signature in response to contraction. Following EPS, 4719 genes were differentially expressed (false discovery rate <0.05) in myotubes from women with PCOS compared to 173 in healthy women. Both groups included genes involved in skeletal muscle contraction. We also determined the effect of two transforming growth factor β (TGFβ) ligands that are elevated in plasma of women with PCOS, TGFβ1 and anti‐Müllerian hormone (AMH), alone and on the EPS‐induced response. While AMH (30 ng/ml) had no effect, TGFβ1 (5 ng/ml) induced the expression of extracellular matrix genes and impaired the exercise‐like transcriptional signature in myotubes from women with and without PCOS in response to EPS by interfering with key processes related to muscle contraction, calcium transport and actin filament. Our findings suggest that while the fundamental gene expression responses of skeletal muscle to contraction is intact in PCOS, circulating factors like TGFβ1 may be responsible for the impaired adaptation to exercise in women with PCOS.
imageKey points
Gene expression responses to in vitro contraction (electrical pulse stimulation, EPS) are altered in myotubes from women with polycystic ovary syndrome (PCOS) compared to healthy controls, with an increased expression of genes related to pro‐inflammatory pathways.
Transforming growth factor β1 (TGFβ1) upregulates genes related to extracellular matrix remodelling and reduces the expression of contractile genes in myotubes, regardless of the donor's health status.
TGFβ1 alters the gene expression response to EPS, providing a possible mechanism for the impaired exercise adaptations in women with PCOS.
Almost half of people on long term antidepressants can stop without relapsing
Authors: Saul Helen , Gursul Deniz , Cassidy Samantha , Duffy Larisa , Lewis Gemma , Lewis Glyn 
Published: June 2022

The studyDuffy L, Clarke CS, Lewis G, et al. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess 2021;25:69.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/almost-half-people-long-term-antidepressants-stop-without-relapse/
Uncovering the burden of hidden ciliopathies in the 100 000 Genomes Project: a reverse phenotyping approach
Authors: Best Sunayna , Yu Jing , Lord Jenny , Roche Matthew , Watson Christopher Mark , Bevers Roel P J , Stuckey Alex , Madhusudhan Savita , Jewell Rosalyn , Sisodiya Sanjay M , Lin Siying , Turner Stephen , Robinson Hannah , Leslie Joseph S , Baple Emma ,   Genomics England Research Consortium, Toomes Carmel , Inglehearn Chris , Wheway Gabrielle , Johnson Colin A 
Published: June 2022

BackgroundThe 100 000 Genomes Project (100K) recruited National Health Service patients with eligible rare diseases and cancer between 2016 and 2018. PanelApp virtual gene panels were applied to whole genome sequencing data according to Human Phenotyping Ontology (HPO) terms entered by recruiting clinicians to guide focused analysis.MethodsWe developed a reverse phenotyping strategy to identify 100K participants with pathogenic variants in nine prioritised disease genes (BBS1, BBS10, ALMS1, OFD1, DYNC2H1, WDR34, NPHP1, TMEM67, CEP290), representative of the full phenotypic spectrum of multisystemic primary ciliopathies. We mapped genotype data ‘backwards’ onto available clinical data to assess potential matches against phenotypes. Participants with novel molecular diagnoses and key clinical features compatible with the identified disease gene were reported to recruiting clinicians.ResultsWe identified 62 reportable molecular diagnoses with variants in these nine ciliopathy genes. Forty-four have been reported by 100K, 5 were previously unreported and 13 are new diagnoses. We identified 11 participants with unreportable, novel molecular diagnoses, who lacked key clinical features to justify reporting to recruiting clinicians. Two participants had likely pathogenic structural variants and one a deep intronic predicted splice variant. These variants would not be prioritised for review by standard 100K diagnostic pipelines.ConclusionReverse phenotyping improves the rate of successful molecular diagnosis for unsolved 100K participants with primary ciliopathies. Previous analyses likely missed these diagnoses because incomplete HPO term entry led to incorrect gene panel choice, meaning that pathogenic variants were not prioritised. Better phenotyping data are therefore essential for accurate variant interpretation and improved patient benefit.
An Interactive Nursing Knowledge System Based on Artificial Intelligence and Its Implications for Neonatal Care Management
Authors: Su Juanjuan , Zhao Suqin 
Published: June 2022

Nowadays, people are paying greater attention to the concept of childcare, and the healthy development of children is humanity’s hope for the future. The newborn stage is the most critical stage of a child’s development, and learning and mastering neonatal care is the first important lesson for parents. To meet the needs of today’s learners and to break the traditional teaching model, this paper develops a set of interactive newborn nursing knowledge system that composes the content of trivial nursing knowledge, reconstructs the knowledge structure system, and provides new teaching methods such as text browsing, 3D animation presentation, picture presentation, video presentation, interactive games, and tests for newborns. Text browsing, 3D animation, image demonstration, video demonstration, and interactive games and tests, among other new teaching methods, give a new teaching mode and method for neonatal nursing education. The study included 158 infants from local hospital. The study was divided into two groups, each with 80 cases: a control group (conventional care) and a study group (quality care management). The outcomes were contrasted and compared. The results revealed that the study group had a lower incidence of nursing defects than the control group, and the difference was statistically significant (

P

0.05

); the study group had a lower incidence of diseases than the control group, and the difference was statistically significant (

P
<
0.05

). The study goes over the complete process of incorporating the instructional display into the interactive newborn care knowledge system. Multimedia techniques and applications were researched throughout the design and production process in order to blend intrinsic knowledge material with digital technology to produce new educational ideas.
Acupuncture and Moxibustion in the Treatment of Adult Diarrhea Irritable Bowel Syndrome: A Network Meta-analysis
Authors: Jiang Xiaoxue , Guo Xiutian , Zhou Jianhua , Ye Sunsong 
Published: June 2022

Objective. This study was aimed at comparing the clinical efficacy of acupuncture and moxibustion on irritable bowel syndrome complicated with diarrhea (IBS-D) in adults and providing guidance for clinical treatment. Methods. PubMed, The Cochrane Library, Embase, CBM, CNKI, and VIP and Wanfang databases were searched to obtain clinical randomized controlled trials (RCTs) on acupuncture and moxibustion in the treatment of IBS-D published from establishment of the database to August 5, 2021. Relevant data were extracted to assess the risk of bias in the included studies, and statistical software Stata 16.0 was used for meta-analysis. Results. Twenty-one studies were eventually included in the network meta-analysis (NMA), including 1626 patients with IBS-D and 8 therapeutic measures. NMA showed that acupuncture [

OR
=
0.35

,

95
%
CI

0.25
,
0.49

,

P
<
0.05

], warming needle moxibustion [

OR
=
6.34

,

95
%
CI

2.83
,
14.21

,

P
<
0.05

], acupuncture+sandwiched moxibustion [

OR
=
12.83

,

95
%
CI

4.49
,
36.64

,

P
<
0.05

], acupuncture+heat-sensitive moxibustion [

OR
=
9.86

,

95
%
CI

1.77
,
55.00

,

P
<
0.05

] were more effective than pinaverium bromide in the treatment of IBS-D. Cumulative ranking probability (SUCRA) showed that the comprehensive efficacy of acupuncture and moxibustion (86.8%) and quality of life (QOL) (70.4%) was the best, while the comprehensive efficacy of pinaverium bromide (2.1%) and QOL (16.3%) was the worst. GV20, GV29, ST 25, ST37, ST36, SP6, LR3, and CV12 were used frequently. Conclusion. Acupuncture+sandwiched moxibustion has the best effect on improving the efficacy and QOL of IBS-D patients. Limited by the number and quality of studies, we still need a large sample, multicenter, and high-quality clinical trials to confirm our findings.
FOXM1 Variant Contributes to Gefitinib Resistance via Activating Wnt/β-Catenin Signal Pathway in Patients with Non–Small Cell Lung Cancer
Authors: Guan Shaoxing , Chen Xi , Chen Youhao , Xie Wen , Liang Heng , Zhu Xia , Yang Yunpeng , Fang Wenfeng , Huang Yan , Zhao Hongyun , Zhuang Wei , Liu Shu , Huang Min , Wang Xueding , Zhang Li 
Published: June 2022

Abstract

Purpose:
Although gefitinib prolonged the progression-free survival (PFS) of patients with non–small cell lung cancer (NSCLC), unpredictable resistance limited its clinical efficacy. Novel predictive biomarkers with explicit mechanisms are urgently needed.

Experimental Design:
A total of 282 patients with NSCLC with gefitinib treatment were randomly assigned in a 7:3 ratio to exploratory (n = 192) and validation (n = 90) cohorts. The candidate polymorphisms were selected with Haploview4.2 in Hapmap and genotyped by a MassARRAY system, and the feature variables were identified through Randomforest Survival analysis. Tanswell and clonogenic assays, base editing and cell-derived tumor xenograft model were performed to uncover the underlying mechanism.

Results:
We found that the germline missense polymorphism rs3742076 (A&gt;G, S628P), located in transactivation domain of FOXM1, was associated with PFS in exploratory (median PFS: GG vs. GA&AA, 9.20 vs. 13.37 months, P = 0.00039, HR = 2.399) and validation (median PFS: GG vs. GA&AA, 8.13 vs. 13.80 months, P = 0.048, HR = 2.628) cohorts. We elucidated that rs3742076_G conferred resistance to gefitinib by increasing protein stability of FOXM1 and facilitating an aggressive phenotype in vitro and in vivo through activating wnt/β-catenin signaling pathway. Meanwhile, FOXM1 level was highly associated with prognosis in patients with EGFR-mutant NSCLC. Mechanistically, FOXM1 rs3742076_G upregulated wnt/β-catenin activity by directly binding to β-catenin in cytoplasm and promoting transcription of β-catenin in nucleus. Remarkably, inhibition of β-catenin markedly reversed rs3742076_G-induced gefitinib resistance and aggressive phenotypes.

Conclusions:
These findings characterized rs3742076_G as a gain-of-function polymorphism in mediating gefitinib resistance and tumor aggressiveness, and highlighted the variant as a predictive biomarker in guiding gefitinib treatment.
Pentecostalism and the Arts of Insistence: Examples from Botswana
Authors: van Dijk Rijk , Molenaar Kim 
Published: June 2022

Abstract
This contribution explores the significance of religious practices that put emphasis on encouraging people to hold their position when others question the ideological or dogmatic elements of their faith. Applying the term ‘religious insistence’, it investigates these practices with a view to the ways in which Pentecostals take a position vis-à-vis the challenges they confront in the sociopolitical domain. Contributing to the study of religious activism, we show that practices of insistence are neither fully resistant nor fully acquiescent with regard to the existing situation. We argue that these practices of holding one’s ground, which we subsume under the term ‘insistence’, represent a specific modality of formulating one’s identity in regard to others that is neither about provoking structural change, as a resistance perspective would emphasise, nor about condoning a structural situation as is and remaining fully acquiescent with it. While in Pentecostal contexts insistence does not take up-front political protest as its main focus, it can still be interpreted as a form of religious activism since it often entails some form of critical response toward a given sociopolitical order or process. By drawing attention to how religious insistence manifests itself in and through Pentecostalism, this contribution proposes to enrich the study of religious activism in Africa and opens up a perspective that addresses assertiveness as a register of expression that differs from resistance and acquiescence.
Ibn al-Jawzī’s Critique of Sufism in Talbīs Iblīs: A Re-Examination
Authors: Held Pascal 
Published: June 2022

Abstract
This study seeks to re-examine Ibn al-Jawzī’s (d. 597/1201) censure of Sufism in his Talbīs Iblīs, a widely-known and frequently cited, but rarely carefully considered work. The article finds that Talbīs Iblīs’ chapter devoted to Sufism does indeed constitute a scathing condemnation of the Sufi tradition, which is however by no means comprehensive and requires moreover certain specifications and clarifications. For example, is Ibn al-Jawzī’s criticism mostly limited to Sufi conduct and practice, especially in public, rather than their ideas and beliefs, and likewise does he use his criticism to highlight commendable forms of piety and mysticism, revealing that he held on to a notion of pristine ascetical and mystical piety himself, which should nonetheless not be mistaken for Sufism. In any case, whether and to what degree one is able to immerse oneself in such forms of piety is according to Talbīs Iblīs to a large extent determined by one’s natural circumstances.
Kitāb al-Ḥujjah ʿAlā Ahl al-Madīnah and the Transition from Regional Schools to Personal
Authors: Melchert Christopher 
Published: June 2022

Abstract
K. al-Ḥujjah ʿalā ahl al-Madīnah by Muḥammad ibn al-Ḥasan al-Shaybānī (d. 189/804-5) is a witness to the state of the regional school of Medina before it had been absorbed by (survived only in) the Mālikī personal school. Schacht asserts that each regional school had its characteristic authorities among the Followers, and the Ḥujjah confirms that, sometimes appealing to Kufan Followers against Medinese, sometimes complaining that the Medinese are not staying loyal to their own Medinese Followers. Sometimes also the Ḥujjah testifies to Mālik’s pre-eminence among the Medinese of his time, sometimes by appealing to him as ‘your faqīh’, with whom the Medinese ought to agree but do not, but mainly as their pre-eminent traditionist. Schacht observed that Shaybānī adduced hadith more often than Abū Yūsuf, and the Ḥujjah often adduces hadith in its arguments against the Medinese. Most often, however, it adduces logical consistency against Medinese positions. Altogether, it suggests that personal schools evolved out of regional by accentuation of the personal element already present in the tradition of regional authorities. By adducing hadith from a wider range of authorities than the Muwaṭṭaʾ, it implicitly argues that Ḥanafi law is superior because it represents the jurisprudence of the whole Empire, not just one centre.
Under the Influence
Authors: Harris Ben 
Published: June 2022

Abstract
This article presents evidence to support an entirely new approach to uncovering the literary structure of the Gospel of Luke and the Acts of the Apostles, a subject which continues to attract attention and divide opinion. It draws on a field of Classical Studies that, although abundant in terms of written sources, remains understudied: ancient pharmacology. At its heart is the established four-part definition of the structural features of medical recipes for composite drugs, and an attempt to demonstrate their influence on the compositional model employed by the author of Luke–Acts. The model is first defined with reference to medical writing in antiquity, before its practical outworking is explored in the Gospel proem (i.e. the formal presentation of the work to its audience). The application of the model in individual pericopes, as well as its extension across two series of pericopes, is then examined within the narrative of the work itself.
An Optimal Atmospheric Circulation Mode in the Arctic Favoring Strong Summertime Sea Ice Melting and Ice–Albedo Feedback
Authors: Baxter Ian , Ding Qinghua 
Published: June 2022

Abstract
The rapid decline of summer Arctic sea ice over the past few decades has been driven by a combination of increasing greenhouse gases and internal variability of the climate system. However, uncertainties remain regarding spatial and temporal characteristics of the optimal internal atmospheric mode that most favors summer sea ice melting on low-frequency time scales. To pinpoint this mode, we conduct a suite of simulations in which atmospheric circulation is constrained by nudging tropospheric Arctic (60°–90°N) winds within the Community Earth System Model, version 1 (CESM1), to those from reanalysis. Each reanalysis year is repeated for over 10 model years using fixed greenhouse gas concentrations and the same initial conditions. Composites show the strongest September sea ice losses are closely preceded by a common June–August (JJA) barotropic anticyclonic circulation in the Arctic favoring shortwave absorption at the surface. Successive years of strong wind-driven melting also enhance declines in Arctic sea ice through enhancement of the ice–albedo feedback, reaching a quasi-equilibrium response after repeated wind forcing for over 5–6 years, as the effectiveness of the wind-driven ice–albedo feedback becomes saturated. Strong melting favored by a similar wind pattern as observations is detected in a long preindustrial simulation and 400-yr paleoclimate reanalysis, suggesting that a summer barotropic anticyclonic wind pattern represents the optimal internal atmospheric mode maximizing sea ice melting in both the model and natural world over a range of time scales. Considering strong contributions of this mode to changes in Arctic climate, a better understanding of its origin and maintenance is vital to improving future projections of Arctic sea ice.
Nationwide Analysis of Biomechanics of Motor Vehicle Collisions Involving Passenger Vehicle and Associated Outcomes: Towards Improving Vehicle Safety Standards and Regulations
Authors: Concepcion Jennifer , Newsome Kevin , Alfaro Sophie , Selvakumar Sruthi , Sen-Crowe Brendon , Vallejo Kevin , Andrade Ryan , Yeager Matthew , Kornblith Lucy , Bilski Tracy , Elkbuli Adel 
Published: June 2022

Background Motor vehicle collisions (MVCs) pose significant mortality and economic burden on the United States. Biomechanics research may guide future vehicle innovation. The objective of this study is to investigate the biomechanics of two-vehicle MVCs involving passenger vehicle (PV) to evaluate associated injury patterns and outcomes including mortality. Methods A retrospective cohort study of cases from the Crash Injury Research Engineering Network database was performed to evaluate the biomechanics (angle of impact, seatbelt use, and airbag deployment) of two-vehicle MVCs involving at least one PV from 2005-2015. Results Out of 629 MVCs evaluated, lateral collisions were most common (49.5%), followed by head-on (41.3%) and rear-end (9.2%) collisions. Thoracic injuries accounted for 30.1%, 31.4%, and 31.1% of injuries in lateral, head-on, and rear-end collisions, respectively, and were the most common body region injured for all collision types. Seatbelt use was associated with shorter ICU stay (10.9 vs 19.1 days, P = .036) and mortality (Cramer’s V = .224, P < .001), but a greater average number of injuries (10.2 injuries vs 8.6 injuries, P = .011). Conclusion Passenger vehicle are commonly involved in MVCs nationwide and efforts are needed to prevent occupant injuries and fatalities. The incorporation of energy-absorbing material into common points of contact within the vehicle interior may decrease the severity of these injuries. Seatbelt use remains a protective factor against MVC-fatalities but is associated with collateral injuries and should be a focus of further innovation.
A Peer Data Benchmarking Intervention to Reduce Opioid Overprescribing: A Randomized Controlled Trial
Authors: Dun Chen , Overton Heidi N. , Walsh Christi M. , Hennayake Sanuri , Wang Peiqi , Fahim Christine , Bicket Mark C. , Makary Martin A. 
Published: June 2022

Background Driving physician behavior change has been an elusive goal for quality improvement efforts aimed at reducing low-value care. We proposed the use of “nudge” interventions at the surgeon level in order to reduce post-surgical opioid overprescribing in accordance with consensus guidelines. Methods We used 2017 Medicare data to identify outlier surgeons. A peer data benchmarking report that showed each surgeon the average number of opioid tablets they prescribed for an open inguinal hernia repair procedure from January 1, 2017 to December 31, 2017. We conducted a 1:1 randomized controlled trial providing outlier surgeons a report of their opioid prescribing patterns for a standard operation compared to the national average and prescribing guidelines. Results There were 489 surgeons randomized to the intervention, of which 180 (36.8%) had data in the post-intervention period. Data was available for 87 surgeons in the intervention group and 93 surgeons in the control group. 97.7% of surgeons in the intervention group reduced their opioid prescribing pattern compared to 95.7% in the control group. Surgeons who received the data benchmarking report intervention prescribed 14.3% less opioids than surgeons in the control group (10.54 (SD 5.34) vs. 12.30 (SD 6.02), P = .04). The intervention was associated with a 1.83 lower mean number of opioid tablets prescribed per patient in the multivariable linear regression model after controlling for other factors (Intervention group vs. control group 95% CI [−3.61, −.04], P = .04). Discussion The implementation of a peer data benchmarking intervention can drive physician behavior change towards high-value care.
Impact of Family Background on Cognitive Skills: An Empirical Investigation
Authors: Sarkar Sreemanta , Chaudhury Anjan Ray , Sinha Madhabendra 
Published: June 2022

This study desires to look at the impact of family background on cognitive skills of the children. On the basis of primary survey of two districts of West Bengal—namely Bankura and Nadia—and using the fathers’ education, occupation and per capita household income as the proxies for family background we have employed multinomial probit and ordered logit regression model for this analysis. The findings reveal that there exists a significant positive association between family background and cognitive skills of the child indicating the existence of poor intergenerational mobility in education in the surveyed region. JEL Codes: I20, I24, I28