bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis
Authors: Giles Jon T , Ogdie Alexis , Gomez-Reino Juan J , Helliwell Philip S , Germino Rebecca , Stockert Lori , Young Pamela , Joseph Wael , Mundayat Rajiv , Graham Daniela , Ritchlin Christopher 
Published: January 2021

ObjectivesThis post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).MethodsData were pooled from two phase 3 studies (NCT01877668;NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg two times a day or placebo, stratified by baseline BMI: <25 kg/m2, ≥25–<30 kg/m2, ≥30–<35 kg/m2or ≥35 kg/m2. Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported.ResultsAnalysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m2). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m2versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m2receiving tofacitinib 5 mg but not 10 mg two times a day.ConclusionTofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m2. Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m2was inconclusive.
A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation
Authors: Lo Yuan-Hung , Kolahi Kevin S. , Du Yuhong , Chang Chiung-Ying , Krokhotin Andrey , Nair Ajay , Sobba Walter D. , Karlsson Kasper , Jones Sunny J. , Longacre Teri A. , Mah Amanda T. , Tercan Bahar , Sockell Alexandra , Xu Hang , Seoane Jose A. , Chen Jin , Shmulevich Ilya , Weissman Jonathan S. , Curtis Christina , Califano Andrea , Fu Haian , Crabtree Gerald R. , Kuo Calvin J. 
Published: January 2021

Abstract

Mutations in ARID1A rank among the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated ARID1A knockout (KO) in primary TP53−/− human gastric organoids induced morphologic dysplasia, tumorigenicity, and mucinous differentiation. Genetic WNT/β-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of ARID1A KO-mediated transformation. ARID1A mutation induced transcriptional regulatory modules characteristic of microsatellite instability and Epstein–Barr virus–associated subtype human gastric cancer, including FOXM1-associated mitotic genes and BIRC5/survivin. Convergently, high-throughput compound screening indicated selective vulnerability of ARID1A-deficient organoids to inhibition of BIRC5/survivin, functionally implicating this pathway as an essential mediator of ARID1A KO-dependent early-stage gastric tumorigenesis. Overall, we define distinct pathways downstream of oncogenic ARID1A mutation, with nonessential WNT-inhibited mucinous differentiation in parallel with essential transcriptional FOXM1/BIRC5-stimulated proliferation, illustrating the general utility of organoid-based forward genetic cancer analysis in human cells.

Significance:
We establish the first human forward genetic modeling of a commonly mutated tumor suppressor gene, ARID1A. Our study integrates diverse modalities including CRISPR/Cas9 genome editing, organoid culture, systems biology, and small-molecule screening to derive novel insights into early transformation mechanisms of ARID1A-deficient gastric cancers.
See related commentary by Zafra and Dow, p. 1327.
This article is highlighted in the In This Issue feature, p. 1307
At the Crossroads: COVID-19 and Immune-Checkpoint Blockade for Cancer
Authors: Garassino Marina Chiara , Ribas Antoni 
Published: January 2021

Abstract
The immunomodulatory effects of immune-checkpoint blockade (ICB) therapy for cancer may act at the crossroads between the need to increase antiviral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease the inflammatory responses in severe cases of coronavirus disease 2019 (COVID-19). There is evidence from preclinical models that blocking programmed death receptor 1 (PD1) protects against RNA virus infections, which suggests that patients with cancer receiving ICB may have lower rates of viral infection. However, given the heterogeneity of patient characteristics, this would be difficult to demonstrate using population-based registries or in clinical trials. Most studies of the impact of ICB therapy on the course of COVID-19 have centered on studying its potential detrimental impact on the course of the COVID-19 infection, in particular on the development of the most severe inflammatory complications. This is a logical concern as it is becoming clear that complications of COVID-19 such as severe respiratory distress syndrome are related to interferon signaling, which is the pathway that leads to expression of the PD1 ligand PD-L1. Therefore, PD1/PD-L1 ICB could potentially increase inflammatory processes, worsening the disease course for patients. However, review of the current evidence does not support the notion that ICB therapy worsens complications from COVID-19, and we conclude that it supports the continued use of ICB therapy during the COVID-19 pandemic provided that we now collect data on the effects of such therapy on COVID-19 vaccination.
Effect of concentration of DHA nutrient-enhanced Artemia on the growth and physiology of the ridgetail white prawn, Exopalaemon carinicauda (Decapoda, Caridea, Palaemonidae)
Authors: Wang Yu , Li Guangguang , Han Zhen , Hu Guangwei , Yan Binlun , Zhang Qingqi , Gao Huan 
Published: January 2021

Abstract
Prawns of the species Exopalaemon carinicauda were fed with Artemia that had been enriched by either 1, or 3, or 5 g/l DHA powder. The feeding dose of Artemia offered to E. carinicauda was calculated according to the water volume, and maintained at 1-3 individuals/ml. After nutritional enrichment, the ratio of DHA content to total fatty acid content in Artemia was the highest (3.32%) after being fed 3 g/l DHA powder. The ratio of DHA content to total fatty acid content in the muscle tissue of E. carinicauda prawns fed with Artemia enhanced with 3 g/l DHA powder was also the highest (4.40%) achieved. Furthermore, when the concentration of fish oil DHA powder was 3 g/l, the survival rate of the prawns was significantly higher than in the control group, with the specific growth rate and weight gain reaching 11.39%/day, and 95.74%, respectively. In addition, the DHA-enhanced Artemia, at different concentrations, increased the non-specific immunity of individuals. The enzyme activity of T-AOC, SOD and AKP in the respective feeding groups of prawns was significantly higher, compared to the control group. Thus, Artemia enriched by 3 g/l DHA powder is proposed as an optimal choice for the offspring breeding of E. carinicauda.
The Centrality and Interpretation of Psalms in Judaism prior to and during Medieval Times: Approaches, Authorship, Genre, and Polemics
Authors: Kalimi Isaac 
Published: January 2021

Abstract
This study discusses the centrality of the book of Psalms among the Jews and in Judaism. It outlines the seven most important and influential rabbinic exegetical works on Psalms, in the period before and during the medieval age: Targum Psalms and Midrash Psalms Shocher Tov, from some time in the Talmudic period; and five prominent medieval commentaries: Saadia Gaon, Moses haCohen ibn Gikatilla, Rashi, Abraham ibn Ezra, and David Kimchi. I briefly introduce each interpretative work and focus on selected aspects: The commentators’ distinct exegetical methods, their approaches to the questions of the authorship and genre of Psalms, and polemics with inside (e.g., Karaites) and outside (e.g., Christians) opponents. The result is to analysis and synthesis their approaches and to show the various trends that rabbinic Psalms interpretation took in these periods.
Reconsideration of Proper Remedies in Investment Arbitration in Light of Recent Cases: Should the Remedy Follow the Primary Obligation?
Authors: Demirkol Berk 
Published: January 2021

Abstract
Remedies available within a particular system are closely connected with the types and diversity of disputes brought to, and with the purpose and the structure of, the special dispute settlement mechanism. Investment arbitration is a mechanism for settlement of disputes between States and foreign investors who have made by definition mid- to long-term projects in the State concerned. Such claims are brought for the protection of private interests of investors, but they are mostly based on public international law obligations and subject to State responsibility principles. Institutional and procedural rules, as well as systemic features of investment arbitration play an important role in the determination of which remedies are available and provide suitable relief within this dispute settlement mechanism. The main argument of this article is that substantive characteristics of primary obligations should be taken into account, along with procedural considerations, in the determination of which remedies are available in investment treaty arbitration.
When Data Transformations are Appropriate or Even Necessary: A Response to Cohen-Shikora, Suh and Bugg (2019)
Authors: Schmidt James R. 
Published: January 2021

Abstract
In this paper, I argue that common data transformations used for statistical modelling are not inherently problematic. Depending on the research question, transformation can be appropriate or even necessary. The paper also discusses the often-overlooked impact of decision-related processes (e.g., rhythmic timing) on behaviour and how such biases can often unintentionally confound research designs. More narrowly, the current paper considers a recent debate about the list-level proportion congruent (llpc) effect, which is the finding that congruency effects (e.g., in the Stroop task) are reduced when most trials are incongruent relative to when most trials are congruent. The llpc effect is typically interpreted as evidence for conflict-driven attentional control (conflict monitoring). However, another view proposes that a rhythmic responding bias (temporal-learning) explains the effect. In a recent article, Cohen-Shikora, Suh, and Bugg (2019) challenged some of the evidence for the latter account. One key question they raise is whether it is appropriate to inverse transform (essentially: de-skew) response times when using linear mixed effect modelling. The authors argued that this transform is problematic and presented a series of analyses that they argued demonstrate both (a) that there are minimal concerns about temporal-learning confounds, and (b) that conflict monitoring clearly contributes to the llpc effect. The present article presents new analyses and demonstrates that neither of these two key conclusions of Cohen-Shikora and colleagues are justified. More global implications for linear mixed effect modelling are discussed, including an analysis of when data transformations should or should not be used.
An Absence of a Relationship between Overt Attention and Emotional Distortions to Time: an Eye Movement Study
Authors: Ogden Ruth S. , Turner Frederieke , Pawling Ralph 
Published: January 2021

Abstract
Emotional distortions to time are consistently reported in laboratory studies; however, their underlying causes remain unclear. One suggestion is that emotion-induced changes in attentional processes may contribute to emotional distortions to time. The current study tested this possibility by examining the relationship between eye movement and perceptions of the duration of emotional events. Participants completed a verbal estimation task in which they estimated the duration of positively, negatively and neutrally valenced images from the International Affective Picture System images. Time to first fixation and dwell time were recorded throughout. The results showed no significant relationships between measures of eye movement and measures of emotional distortion to time, despite the emotion manipulation successfully influencing the time before the participants first fixated on the to-be-timed stimulus. This suggests that for suprasecond intervals emotion-induced changes in overt attention processing do not contribute towards emotional distortions to time.
Impact of 4D-Var Data Assimilation on Performance of the Coupled Land–Atmosphere Model WRF–TOPX: A Case Study of a Flood Event in the Wangjiaba Watershed, China
Authors: Yi Lu , Yong Bin , Chen Junxu , Zheng Ziyan , Li Ling 
Published: January 2021

AbstractTo assess the impact of four-dimensional variational (4D-Var) data assimilation on the performance of a land–atmosphere coupled model, the satellite precipitation of the Integrated Multisatellite Retrievals for Global Precipitation Measurement (IMERG) was assimilated into the Weather Research Forecast (WRF) Model, and the WRF was coupled to the hydrological model TOPX. Precipitation and evaporation were both investigated as connecting elements in the coupled model WRF–TOPX. Differing in whether the 4D-Var data assimilation and evaporation were applied, one control experiment and four experiments were performed to simulate a historical flood event that happened in the Wangjiaba watershed in eastern China. The key hydrological variables of precipitation, potential evaporation, soil moisture, and discharge in the studied flood process were evaluated. The results showed that 1) the 4D-Var data assimilation with the IMERG could reduce both the overestimations of the WRF-predicted precipitation and potential evaporation; 2) the applied 4D-Var data assimilation could improve considerably the accuracy of the soil moisture and discharges from the coupled model WRF–TOPX; and 3) evaporation was also an important factor to influence the net precipitation to affect the performance of the coupled land–atmosphere model. With the two connecting elements of precipitation and evaporation, the 4D-Var assimilation based on IMERG could improve the Nash–Sutcliffe coefficient of the coupled model WRF–TOPX from 0.483 to 0.521 at the hourly scale. These investigations can provide important implications for the land–atmosphere coupling with both the precipitation and evaporation and using the 4D-Var data assimilation with IMERG for flood simulation at a large scale.
Inter-firm power relations and working conditions under new production models
Authors: Paz María J , Rísquez Mario , Ruiz-Gálvez María E 
Published: January 2021

AbstractIn investigating recent changes to the automotive industry production process, such as modularisation, our work emphasises the process of fragmentation of production as a configuring element of inter-firm power relationships, and as an explanatory element in working conditions. From a theoretical framework focused on power relations, we analyse by way of a selected case study how the capabilities of companies and their network positions, together with the agency of labour, shape the power relations that influence the evolution of working conditions. The study does indeed find relevant changes to inter-firm relationships, for example, within networks of assemblers and suppliers, but without a consequent re-balancing of power. This finding serves to explain differences in the evolution of working conditions between distinct companies, these conditions being fully functional to a strategy for profitability and thus difficult to reverse.
Student outcomes of an international learning collaborative to develop patient safety and quality competencies in nursing
Authors: Sanford Julie , Argenbright Christine , Sherwood Gwen , Jordan Portia J , Jiménez-Herrera Maria F , Bengtsson Mariette , Moriyama Michiko , Peng Lui Lee , McDonald Maria 
Published: January 2021

Background Patient harm is a global crisis fueling negative outcomes for patients around the world. Working together in an international learning collaborative fostered learning with, from and about each other to develop evidence-based strategies for developing quality and safety competencies in nursing. Aims To report student outcomes from an international learning collaborative focused on patient safety using the Quality and Safety Education for Nurses competency framework. Methods A global consortium of nursing faculty created an international learning collaborative and designed educational strategies for an online pre-workshop and a 10-day in-person experience for 21 undergraduate and graduate nursing students from six countries. A retrospective pre-test post-test survey measured participants’ confidence levels of patient safety competence using the health professional education in patient safety survey and content analysis of daily reflective writings. Results Statistical analysis revealed student confidence levels improved across all eight areas of safe practice comparing-pre and post-education (significance, alpha of P < 0.05). Two overarching themes, reactions to shared learning experiences and shared areas of learning and development, reflected Quality and Safety Education for Nurses competencies and a new cultural understanding. Conclusions The international learning collaborative demonstrated that cross-border learning opportunities can foster global development of quality and safety outcome goals.
Assessing the impact of a new central venous access device training progam for nurses: A quasi-experimental evaluation study
Authors: Burt Wendy , Spowart Lucy 
Published: January 2021

Background: Central venous access devices (CVAD) are widely used for both long- and short-term purposes within healthcare and are suitable for both hospital and community management. Training is essential in the prevention of complications such as infection. Objectives: To assess the impact of a new standardised education programme on clinical practice and patient care. The new education programme was introduced to all registered nurses working in one care group within an acute healthcare Trust with the aim of improving knowledge and skills and reduce CVAD-related complications. Methods: This retrospective quasi-experimental evaluation study analyses the impact of the programme on direct patient care. Secondary data sources such as infection incidence rates and CVAD clinical audits were used to identify and measure the relationship between staff confidence, infection incidence and care audit results. Data spanning a two-year period were used to capture an accurate representation of the patient group. Results: Improvements in audited care elements and a reduction of infection incidences were evident during and after implementation of the education programme. This was reflective of the self-reported increased confidence and knowledge and skill acquisition from staff who attended the programme. Discussion: Recommendations have been made including a review of the education content to target all key elements and promotion of an end goal with regular feedback to staff reinforcing the importance. The challenge of using secondary data sources also highlighted the need for quality improvements in the current care audit process.
Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis
Authors: Tang Jinshuo , Liu Tong , Wen Xinggui , Zhou Zhongsheng , Yan Jingtong , Gao Jianpeng , Zuo Jianlin 
Published: January 2021

AbstractOsteoarthritis (OA) is a chronic inflammatory disease that is associated with articular cartilage destruction, subchondral bone alterations, synovitis, and even joint deformity and the loss of joint function. Although current basic research on the pathogenesis of OA has made remarkable progress, our understanding of this disease still needs to be further improved. Recent studies have shown that the estrogen-related receptor (ERR) family members ERRα and ERRγ may play significant roles in the pathogenesis of OA. In this review, we refer to the latest research on ERRs and the pathogenesis of OA, elucidate the structure and physiopathological functions of the ERR orphan nuclear receptor family, and systematically examine the relationship between ERRs and OA at the molecular level. Moreover, we also discuss and predict the capacity of ERRs as potential targets in the clinical treatment of OA.
Relationships between inappropriate eating habits and problematic alcohol use, cigarette and waterpipe dependence among male adolescents in Lebanon
Authors: Berro Jana , Akel Marwan , Hallit Souheil , Obeid Sahar 
Published: January 2021

Abstract
Background
it is important to investigate the relationship between disordered eating in male adolescents and smoking and alcohol consumption as they are risk factors to other diseases as well. For example, high levels of alcohol accompanied by the acidic damage and nutritional deficit exhibited in people with disordered eating habits - due to induced vomiting - has been shown to increase risk of esophageal cancer. Considering the very few studies done on disordered eating prevailing in males and the prevalence of smoking and drinking habits, our study aims to investigate the correlation between inappropriate eating habits and one’s dependence on cigarettes, waterpipes, and alcohol all the while focusing on male adolescents.

Methods
This was a cross-sectional observational study that enrolled 389 male students (13–17 years of age) drawn from five Lebanese schools between October and December 2019.

Results
The MANCOVA analysis was performed taking the addiction scales as the dependent variables and the EAT-26 score as an independent variable, adjusting for the covariates (age, BMI and household crowding index). Higher EAT-26 scores (more inappropriate eating attitudes) were significantly associated with higher waterpipe dependence (B = 0.11; CI 0.06–0.17) and more problematic alcohol use (B = 0.08; CI 0.04–0.12), but not cigarette dependence.

Conclusions
This study revealed an association between inappropriate eating and increased drinking and smoking the waterpipe, but not cigarettes. The manifestation of inappropriate eating habits was found to be significant among male adolescents; in the literature, this is also true for female adolescents. In Lebanon, the engagement of adolescents in alcohol drinking and waterpipe smoking is frequent as they are accessible due to the lack of law enforcement and supervision in the country. In addition, while this study found an association between inappropriate eating habits and dependency on smoking and drinking, further investigation should be done on the role of one’s psychology in their exhibition of disordered eating as means to prevent the manifestation of these habits.