bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of filgotinib for Japanese patients with RA and inadequate response to MTX: FINCH 1 52-week results and FINCH 4 48-week results
Authors: Tanaka Yoshiya , Matsubara Tsukasa , Atsumi Tatsuya , Amano Koichi , Ishiguro Naoki , Sugiyama Eiji , Yamaoka Kunihiro , Combe Bernard G , Kivitz Alan J , Bae Sang-Cheol , Keystone Edward C , Nash Peter , Genovese Mark , Matzkies Franziska , Bartok Beatrix , Pechonkina Alena , Kondo Akira , Ye Lei , Gong Qi , Tasset Chantal , Takeuchi Tsutomu 
Published: August 2022

ABSTRACT

Objectives
To present safety and efficacy of the JAK1 preferential inhibitor filgotinib in Japanese patients with prior inadequate response (IR) to methotrexate (MTX) from a 52-week randomised controlled parent study (PS) and long-term extension (LTE) through June 2020.

Methods
The PS (NCT02889796) randomised MTX-IR patients to filgotinib 200 (FIL200) or 100 mg (FIL100), adalimumab (ADA) 40 mg, or placebo; all took stable background MTX. At week (W) 24, placebo patients were rerandomised to FIL200 or FIL100. The primary endpoint was W12 American College of Rheumatology 20% improvement; safety was assessed by adverse event (AE) reporting. For the LTE (NCT03025308), eligible filgotinib patients continued FIL200/FIL100; ADA patients were rerandomised (blinded) to FIL200 or FIL100; all continued MTX.

Results
In all, 114/147 Japanese patients completed the PS, 115 enrolled in LTE, and 103 remained on study in June 2020. In the PS, AEs were consistent with the overall population, and W24 efficacy was maintained or improved through W52, comparable with the overall population. LTE AE incidences were similar between doses; filgotinib efficacy was consistent from baseline to W48 and similar between PS ADA and filgotinib patients.

Conclusions
Among MTX-IR Japanese patients, filgotinib maintained efficacy over 1 year; LTE safety was consistent with the PS.
Robust counterselection and advanced λRed recombineering enable markerless chromosomal integration of large heterologous constructs
Authors: Bubnov Dmitrii M , Yuzbashev Tigran V , Khozov Andrey A , Melkina Olga E , Vybornaya Tatiana V , Stan Guy-Bart , Sineoky Sergey P 
Published: August 2022

Abstract
Despite advances in bacterial genome engineering, delivery of large synthetic constructs remains challenging in practice. In this study, we propose a straightforward and robust approach for the markerless integration of DNA fragments encoding whole metabolic pathways into the genome. This approach relies on the replacement of a counterselection marker with cargo DNA cassettes via λRed recombineering. We employed a counterselection strategy involving a genetic circuit based on the CI repressor of λ phage. Our design ensures elimination of most spontaneous mutants, and thus provides a counterselection stringency close to the maximum possible. We improved the efficiency of integrating long PCR-generated cassettes by exploiting the Ocr antirestriction function of T7 phage, which completely prevents degradation of unmethylated DNA by restriction endonucleases in wild-type bacteria. The employment of highly restrictive counterselection and ocr-assisted λRed recombineering allowed markerless integration of operon-sized cassettes into arbitrary genomic loci of four enterobacterial species with an efficiency of 50–100%. In the case of Escherichia coli, our strategy ensures simple combination of markerless mutations in a single strain via P1 transduction. Overall, the proposed approach can serve as a general tool for synthetic biology and metabolic engineering in a range of bacterial hosts.
Molecular basis of anti-CRISPR operon repression by Aca10
Authors: Lee So Yeon , Birkholz Nils , Fineran Peter C , Park Hyun Ho 
Published: August 2022

Abstract
CRISPR-Cas systems are bacterial defense systems for fighting against invaders such as bacteriophages and mobile genetic elements. To escape destruction by these bacterial immune systems, phages have co-evolved multiple anti-CRISPR (Acr) proteins, which inhibit CRISPR-Cas function. Many acr genes form an operon with genes encoding transcriptional regulators, called anti-CRISPR-associated (Aca) proteins. Aca10 is the most recently discovered Aca family that is encoded within an operon containing acrIC7 and acrIC6 in Pseudomonas citronellolis. Here, we report the high-resolution crystal structure of an Aca10 protein to unveil the molecular basis of transcriptional repressor role of Aca10 in the acrIC7-acrIC6-aca10 operon. We identified that Aca10 forms a dimer in solution, which is critical for binding specific DNA. We also showed that Aca10 directly recognizes a 21 bp palindromic sequence in the promoter of the acr operon. Finally, we revealed that R44 of Aca10 is a critical residue involved in the DNA binding, which likely results in a high degree of DNA bending.
Mining bacterial NGS data vastly expands the complete genomes of temperate phages
Authors: Zhang Xianglilan , Wang Ruohan , Xie Xiangcheng , Hu Yunjia , Wang Jianping , Sun Qiang , Feng Xikang , Lin Wei , Tong Shanwei , Yan Wei , Wen Huiqi , Wang Mengyao , Zhai Shixiang , Sun Cheng , Wang Fangyi , Niu Qi , Kropinski Andrew M , Cui Yujun , Jiang Xiaofang , Peng Shaoliang , Li Shuaicheng , Tong Yigang 
Published: August 2022

Abstract
Temperate phages (active prophages induced from bacteria) help control pathogenicity, modulate community structure, and maintain gut homeostasis. Complete phage genome sequences are indispensable for understanding phage biology. Traditional plaque techniques are inapplicable to temperate phages due to their lysogenicity, curbing their identification and characterization. Existing bioinformatics tools for prophage prediction usually fail to detect accurate and complete temperate phage genomes. This study proposes a novel computational temperate phage detection method (TemPhD) mining both the integrated active prophages and their spontaneously induced forms (temperate phages) from next-generation sequencing raw data. Applying the method to the available dataset resulted in 192 326 complete temperate phage genomes with different host species, expanding the existing number of complete temperate phage genomes by more than 100-fold. The wet-lab experiments demonstrated that TemPhD can accurately determine the complete genome sequences of the temperate phages, with exact flanking sites, outperforming other state-of-the-art prophage prediction methods. Our analysis indicates that temperate phages are likely to function in the microbial evolution by (i) cross-infecting different bacterial host species; (ii) transferring antibiotic resistance and virulence genes and (iii) interacting with hosts through restriction-modification and CRISPR/anti-CRISPR systems. This work provides a comprehensively complete temperate phage genome database and relevant information, which can serve as a valuable resource for phage research.
Incidence and survival of choroid plexus tumors in the United States
Authors: Takaoka Kailey , Cioffi Gino , Waite Kristin A , Finlay Jonathan L , Landi Daniel , Greppin Kaitlyn , Kruchko Carol , Ostrom Quinn T , Barnholtz-Sloan Jill S 
Published: August 2022

Abstract

Background
There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States.

Methods
Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDC’s National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016.

Results
CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033–0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008–0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005–0.006). Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged. Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR: 5.23, 95% CI: 4.05–7.54, P &lt; .001).

Conclusions
This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis.
Prevalence of Medical Contraindications to Nirmatrelvir/Ritonavir in a Cohort of Hospitalized and Nonhospitalized Patients With COVID-19
Authors: Lim Sarah , Tignanelli Christopher J , Hoertel Nicolas , Boulware David R , Usher Michael G 
Published: August 2022

Abstract
This analysis describes the prevalence of contraindications to nirmatrelvir/ritonavir among 66 007 patients with coronavirus disease 2019 in a large health care system. A possible contradiction was present in 9830 patients (14.8%), with the prevalence of contraindications increasing with higher acuity of illness.
Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation
Authors: Handley Guy 
Published: August 2022

AbstractHuman herpesvirus 6 (HHV-6) frequently reactivates after allogeneic stem cell transplantation (SCT). Most patients are asymptomatic and viremia often resolves without therapy; however, transplant-related complications may be associated with reactivation. Multiple presentations have been attributed to HHV-6 reactivation after SCT including encephalitis. Several strategies have been trialed to reduce such risks or complications. Challenges exist with prospective monitoring strategies, and established thresholds of high-level reactivation may be limited. Three published guidelines and extensive trials focusing on preemptive and prophylactic strategies are reviewed. Future areas of investigation and high-risk populations are described. Existing trials and testing platforms have significant limitations, and to date no clear benefit for a preemptive or prophylactic intervention has been demonstrated.
Estimating the impact of menstrual poverty on adolescents in Nova Scotia
Authors: Lukindo Mary , Price Victoria , Pike Meghan 
Published: August 2022

Abstract

Background
Menstrual poverty is defined as the inability of people who menstruate to obtain menstrual products due to financial burden. The impact of menstrual poverty is not well studied in developed countries.

Objectives
This study aims to estimate the impact of menstrual poverty on adolescents who reside in Nova Scotia (NS), Canada.

Methods
A web-based, 25-item questionnaire, the adolescent Menstrual Poverty Questionnaire (aMPQ), was developed and distributed via social media. Adolescents less than 18 years of age, English-speaking and living in NS were eligible to complete the questionnaire. Data were analysed using descriptive analysis.

Results
Four hundred and twenty adolescents completed the questionnaire, with a mean age of 16.1 years (14.4–17.9 years). Results revealed that 65% of respondents do not always have enough money to buy menstrual products. This led to unsafe menstrual hygiene practices including using alternatives for menstrual products (e.g., rags), washing disposable menstrual products, and/or wearing products for longer than intended. Forty percent of respondents reported lack of affordability of menstrual products as a cause for school absenteeism and lack of participation in sport/social activities. Seventy percent of respondents felt embarrassed to ask for products even when they are provided for free, and almost all supported the idea of having freely available menstrual products in public washrooms.

Conclusions
This study determined that menstrual poverty impacts adolescents in Nova Scotia. To address menstrual poverty, menstrual products should be freely available in all public washrooms, as this will provide unrestricted access to menstruators and promote their full participation in society.
Food insecurity in households of children receiving care at a paediatric obesity management clinic in Montreal: Overall prevalence and changes associated with the COVID-19 pandemic
Authors: Cyrenne-Dussault Marie , Sirois Maude , St-Pierre Julie , Drouin-Chartier Jean-Philippe 
Published: August 2022

Abstract

Objectives
Food insecurity and paediatric obesity are two major public health issues in Canada that may have been exacerbated by the COVID-19 pandemic. We assessed food insecurity and its correlates among households of children receiving care at a paediatric obesity management clinic in Montreal. We also assessed whether the prevalence of food insecurity among households of children who received care during the COVID-19 pandemic differed from those who received care before it.

Methods
This is a retrospective, cross-sectional analysis of medical records of children (2 to 17 years) who received care at a paediatric obesity management clinic in Montreal (Maison de santé prévention – Approche 180 [MSP-180]). Children’s household food security status was assessed using Health Canada’s Household Food Security Survey Module.

Results
Among the 253 children included in the study, 102 (40.3%) lived in households with moderate (n=89; 35.2%) or severe food insecurity (n=13; 5.1%). Food insecurity was more prevalent in households of children who were first- or second-generation immigrants compared with those who were third generation or more (48.3% versus 30.1%; P=0.03). Prevalence of food insecurity among households of children who received care during the COVID-19 pandemic was 5.5% higher than among those who received care before the pandemic, but the difference was not statistically significant (39.6% versus 45.1%; P=0.65).

Conclusions
Forty per cent of children treated at this paediatric obesity clinic lived in a food insecure household. This prevalence may have increased during the first year of the COVID-19 pandemic, but statistical power was insufficient to confirm it.
Effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with juvenile-onset inflammatory rheumatic diseases
Authors: Ziv Amit , Heshin-Bekenstein Merav , Haviv Ruby , Kivity Shaye , Netzer Doron , Yaron Shlomit , Schur Yoav , Egert Tsipi , Egert Yona , Sela Yaron , Hashkes Philip J , Uziel Yosef 
Published: August 2022

AbstractObjectivesThe effectiveness of the BNT162b2 mRNA COVID-19 vaccine for adolescents with juvenile-onset inflammatory or immune rheumatic diseases (IRDs) is unknown. Several studies have suggested attenuated immunogenicity in patients with IRD. This study evaluated the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing COVID-19 infection in adolescents with juvenile-onset IRD compared with controls without immune rheumatic disease.MethodsWe used data from Clalit Health Services, the largest health-care organization in Israel, to conduct an observational cohort study from February to December 2021, involving 12–18 year-old adolescents diagnosed with IRD. Study outcomes included documented COVID-19 infection in relation to vaccination status and immunomodulatory therapy. We estimated vaccine effectiveness as one minus the risk ratio. Adolescents aged 12–18 years without immune rheumatic disease served as controls.ResultsA total of 1639 adolescents with IRD (juvenile idiopathic arthritis, SLE, or familial Mediterranean fever) were included and compared with 524 471 adolescents in the same age range without IRD. There was no difference in COVID-19 infection rates after the second dose of vaccine between those with IRD and controls (2.1% vs 2.1% respectively, P = 0.99). The estimated vaccine effectiveness for adolescents with IRD was 76.3% after the first dose, 94.8% after the second and 99.2% after the third dose.ConclusionWe found that the BNT162b2 mRNA vaccine was similarly effective against COVID-19 infection in adolescents with and without IRD. Immunomodulatory therapy did not affect its effectiveness. These results can encourage adolescents with IRD to get vaccinated against COVID-19.
Mothers’ and daughters’ employment in Europe. A comparative analysis
Authors: Berloffa Gabriella , Matteazzi Eleonora , Şandor Alina , Villa Paola 
Published: August 2022

Abstract
This article analyzes the intergenerational correlation of employment between young women (at about 30 years of age) and their mothers (when their daughters were about 14 years old), using 2011 European Union Survey on Income and Living Conditions data. It examines the extent to which this correlation varies across 19 European countries and is associated with the socioeconomic context at the national level. Having grown up with a working mother is associated with a sizeable increase in the daughters’ employment probability in almost all countries, with greater effect for women with children. For this group, the intergenerational correlation is smaller in countries where the policy context is less favorable to maternal employment. It is crucial to promote gender equality, challenging individuals’ gender stereotypes through education and in society at large, and create conditions that allow young women’s preferences for work to be realized, enhancing policies that favor a balanced sharing of unpaid work.
When Pandemic Interferes with Work: Psychological Capital and Mental Health of Social Workers during COVID-19
Authors: Ho Henry C Y , Chui On Sang , Chan Ying Chuen 
Published: August 2022

Abstract
The impact of the COVID-19 pandemic is not only limited to physical health but also extends to various aspects of everyday life. The present study proposes that the prolonged pandemic can lead to pandemic–work conflict (PWC). The article examines how the pandemic interferes with work, the association between PWC and mental health, and the underlying mechanism of this process. A total of 303 full-time social workers in Hong Kong responded to measures on PWC, psychological capital (PsyCap), and anxiety and depressive symptoms. Data were collected between February and April 2020, when the COVID-19 outbreak was beginning to worsen; 15.8 percent and 14.9 percent of the participants reported mild to severe anxiety and depression, respectively. Time-based PWC was positively associated and strain-based PWC was negatively associated with PsyCap, which was in turn negatively associated with anxiety and depressive symptoms. PsyCap was a significant mediator of these relationships. The findings suggest that the relationship between strain-based PWC and psychological distress can be explained by PsyCap, whereby the depletion of psychological resources may contribute to anxiety and depressive symptoms. Positive psychological resources may be an intervening point for promoting mental health among the social services workforce.
Principal forms of commercial trusts in the UK and the rethinking of traditional approaches
Authors: Zhang Ruiqiao 
Published: August 2022

Abstract
Trusts, which originated in common law and are used to protect family landholdings over generations, have developed into a vehicle that is more often used for commercial purposes. This shift has occurred without any systematic understanding of in what form and to what extent trusts can be adopted in a commercial context. Furthermore, few have considered whether existing trust law can adequately govern commercial trusts; that is, whether or not the commercial use of trusts requires a redeveloped trust law regime, distinguished from traditional approaches. This article offers a critical analysis of these issues, identifying and categorising the principal forms of commercial trusts that are currently employed in the UK. It argues that, given the different settings and contexts in which commercial trusts are found, trust law should be developed to serve the way in which trusts are now used in a commercial context.
Monensin supplementation during late gestation of beef cows alters maternal plasma concentrations of insulin-like growth factors 1 and 2 and enhances offspring preweaning growth
Authors: Vedovatto Marcelo , Izquierdo Vinicius , Palmer Elizabeth , Oliveira Rhaiza A , Silva Hiran M , Vendramini João M B , Moriel Philipe 
Published: August 2022

AbstractThis study evaluated the effects of maternal prepartum supplementation of dried distillers grains (DDG), with or without monensin addition, on maternal performance and physiology and offspring preweaning growth. On day 0 (approximately 197 ± 4 d prepartum), 150 multiparous, Brangus crossbred beef cows were ranked by their initial body weight (BW; 524 ± 51 kg) and body condition score (BCS; 5.0 ± 0.63), and then randomly assigned into one of 15 bahiagrass (Paspalum notatum) pastures (10 cows and 8.1 ha/pasture). Maternal treatments were randomly assigned to pastures (5 pastures/treatment) and consisted of no prepartum supplementation of DDG (NOSUP) or supplementation of DDG at 1 kg/cow/d (dry matter basis; DM) added with 0 mg (SUP) or 200 mg/d of monensin (SUPMO) from days 0 to 77. Effects of maternal treatment and maternal treatment × day of the study were not detected (P ≥ 0.63) for any forage data. Cow BCS on day 35 and near calving (day 77) did not differ (P ≥ 0.19) between SUP and SUPMO cows but both groups had greater (P ≤ 0.001) BCS compared with NOSUP cows. Cow BCS at the start of the breeding season (day 142) and on day 168 were the greatest (P &lt; 0.0001) for SUPMO cows, least for NOSUP cows, and intermediate (P ≤ 0.02) for SUP cows. Maternal plasma concentrations of glucose did not differ (P ≥ 0.25) among treatments. Plasma concentrations of insulin-like growth factor 1 (IGF-1) on day 77 were the least for NOSUP cows (P ≤ 0.05) and did not differ (P = 0.66) between SUP and SUPMO cows, whereas plasma concentrations of IGF-2 on days 35 and 77 were greatest (P ≤ 0.05) for SUPMO cows and did not differ (P ≥ 0.60) between NOSUP and SUP cows. Birth BW of first offspring did not differ (P = 0.77) between SUP and SUPMO calves but NOSUP calves were lighter at birth (P ≤ 0.05) compared with SUP and SUPMO calves. Percentage of cows pregnant with a second offspring did not differ (P = 0.72) between SUP and SUPMO cows and were the least for NOSUP cows (P ≤ 0.05). First offspring BW at weaning (day 325) was greatest (P ≤ 0.05) for SUPMO calves, least for NOSUP calves, and intermediate for SUP calves. Therefore, adding monensin into prepartum DDG supplements for Bos indicus-influenced beef cows did not increase cow prepartum BCS but led to greatest offspring preweaning growth, likely by modulating maternal plasma concentrations of IGF-1 and IGF-2 during gestation.