bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of BCG_2432c from the Bacillus Calmette‐Guérin vaccine enhances autophagy‐mediated immunity against tuberculosis
Authors: Wu Yaqi , Tian Maopeng , Zhang Yandi , Peng Huiming , Lei Qing , Yuan Xuefeng , Liu Shijie , Xiong Yulong , Lin Xiaosong , Jo‐Lewis Banga Ndzouboukou , Yao Zongjie , Fu Hui , Fan Xionglin 
Published: October 2021

AbstractBackgroundMycobacterium bovis bacillus Calmette‐Guérin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent M. bovis strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy.MethodsThree genes, BCG_3174, BCG_1782, and BCG_2432c, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of M. bovis and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo.ResultsOf the three identified genes, only the disruption of BCG_2432c, namely ΔBCG_2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. ΔBCG_2432c showed a stronger ability to trigger intracellular ROS‐mediated complete autophagic flux in infected THP‐1 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN‐γ+ CD4+ TEM and IL‐2+CD4+TCM cells in the spleens and lungs of ΔBCG_2432c‐vaccinated mice.ConclusionsThe insufficient efficacy of the BCG vaccine is attributable to the important autophagy‐inhibition gene BCG_2432c that blocks the autophagosome‐lysosome pathway of antigen presentation. ΔBCG_2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB.
External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia
Authors: Corral Alaejos Álvaro , Zarzuelo Castañeda Aránzazu , Jiménez Cabrera Silvia , Sánchez‐Guijo Fermín , Otero María José , Pérez‐Blanco Jonás Samuel 
Published: October 2021

AimsImatinib is considered the standard first‐line treatment in newly diagnosed patients with chronic‐phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model‐based predictions through Bayesian forecasting computed by each model at different treatment occasions.MethodsA literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction‐ and simulated‐based diagnostics together with Bayesian forecasting analysis.ResultsFourteen imatinib popPK studies were included for model‐performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady‐state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction‐based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter‐occasion variability contributed to reducing bias and improving individual model‐based predictions.ConclusionsImatinib popPK studies developed in Caucasian subjects including α1‐acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model‐based individual prediction performance trough Bayesian forecasting.
Effect of renal impairment on the pharmacokinetics and safety of dorzagliatin, a novel dual‐acting glucokinase activator
Authors: Miao Jia , Fu Ping , Ren Shuang , Hu Chao , Wang Ying , Jiao Chengfeng , Li Ping , zhao Yu , Tang Cui , Qian Yuli , Yang Rong , Dong Yanli , Rong Jing , Wang Yaohui , Jin Xiaowei , Sun Yu , Chen Li 
Published: October 2021

AbstractDorzagliatin is a novel allosteric glucokinase activator targeting both pancreatic and hepatic glucokinase currently under clinical investigation for treatment of type 2 diabetes (T2D). This study aimed to investigate the effect of renal impairment (RI) on dorzagliatin’s pharmacokinetics (PKs) and safety, and to guide appropriate clinical dosing in patients with diabetic kidney disease, including end‐stage renal disease (ESRD). Based on the results from physiologically‐based pharmacokinetic modeling, the predicted outcome of RI on dorzagliatin PK property would be minimum that the plasma exposure area under concentration (AUC) of dorzagliatin in patients with ESRD would increase at about 30% with minimal change in peak concentration (Cmax) comparing to those in healthy volunteers (HVs). To definitively confirm the prediction, a two‐part RI study was designed and conducted based on regulatory guidance starting with the patients with ESRD matched with HVs. Results of the RI study showed minimum difference between patients with ESRD and HVs with respect to dorzagliatin exposure with geometric mean ratio of ESRD to HV at 0.81 for Cmax and 1.11 for AUC. The elimination half‐life, volume of distribution, and systemic clearance for dorzagliatin were similar between the two groups. Dorzagliatin was well‐tolerated in patients with ESRD during the study. Therefore, RI showed no significant impact on dorzagliatin PK, suggesting that dorzagliatin can be readily used in patients with T2D at all stages of RI without need for dose adjustment.
Neurodevelopmental profile of HIVEP2‐related disorder
Authors: Mo Alisa , Snyder Leeanne G , Babington Owen , Chung Wendy K , Sahin Mustafa , Srivastava Siddharth 
Published: October 2021

AimTo characterize the neurodevelopmental profile and systemic features of HIVEP2‐related disorder.MethodThis study used retrospective medical history and standardized assessment data from Simons Searchlight to describe the clinical characteristics of 12 individuals (eight males, four females; age range 3y 3mo–12y 8mo; mean age [SD] 7y 7mo [2y 11mo]) with pathogenic HIVEP2 variants, focusing on their levels of adaptive functioning, autism symptomology, and emotional and behavioral characteristics.ResultsCommon features included neonatal complications, hypotonia, developmental delay, intellectual disability, language impairment, gastroesophageal reflux, and strabismus. A minority of individuals had epilepsy, microcephaly, or a movement disorder. Based on the Vineland Adaptive Behavior Scales, Second Edition, affected individuals showed impairments in adaptive behavior (mean composite standard score [SD] 56.4 [10.2]; n=8). The cohort also had significant impairments in social problems, as measured by the Social Responsiveness Scale, Second Edition (mean total score [SD] 76.4 [11.3]; n=10) and clinically significant emotional and behavioral difficulties, as measured by the Child Behavior Checklist for ages 6–18 (mean total T score [SD] 66.9 [8.2]; n=8).InterpretationThese results show that individuals with HIVEP2‐related disorder have impairments in adaptive and social‐related behaviors as well as difficulties in emotional and behavioral symptoms.
Revisiting global imbalances: A comparative analysis of income and consumption inequality
Authors: Sheng Li , Zhang Zhaoyong 
Published: October 2021

AbstractThis article presents a simple model that reveals the reverse relation of the ratio of current account balance to inequality in income and consumption. Consumption smoothing schemes have been aggregated, among which the linchpin is a policy intervention that mitigates the worsening consumption inequality problem. However, in the long run, short‐sighted policies could have a corresponding impact on current accounts.
Using intersectionality to explore social inequalities amongst Christian family migrants in China
Authors: Gao Quan , Hopkins Peter 
Published: October 2021

AbstractIn this paper, we explore how an intersectional frame offers new insights into the issue of social inequalities in relation to family migration. We bring research about family migration and intersectionality into conversation with one another by empirically examining the experiences of rural Christian family migrants in Shenzhen, China. We consider how neoliberal labour regimes and the Chinese state's project of building a secular and modernised state operates through an intersectional process of de‐familiarisation that turns rural migrants into gendered, class‐based, atomised labouring subjects. We argue that a more nuanced analysis of social inequalities in family migration could usefully focus on the intersectional processes within and among migrant families.
Turning Big Brother upside down: Revisiting surveillance from Latin America
Authors: Ragas José 
Published: October 2021

AbstractThis essay discusses the emergence of a vibrant body of research embracing surveillance in Modern Latin America. By focusing on a specific yet complex region, scholars have expanded the original framework associated with the term, applying this new lens to periods ranging from after the Wars of Independence to contemporary episodes. Moreover, the examination of surveillance in this region reveals how researchers have engaged not only with trending research but their willingness to respond to the social, political, and technological phenomena that have become more visible since the 9/11 terrorist attacks and the implementation of a new paradigm based on state security. This concern has become augmented with the revelations on the role of the National Security Agency and social media companies obtaining data from citizens. I conclude by suggesting new avenues for this nascent scholarship to move away from its rigid Orwellian nature and turn surveillance into a more flexible analytical tool.
ENDOGENOUS LABOR MARKET CYCLES
Authors: Li Yunan , Wang Cheng 
Published: October 2021

AbstractWe offer a new way of thinking about labor market fluctuations. In a perfectly stationary physical environment of the labor market, moral hazard and competition in long‐term contracting generate cycles in market tightness, which may induce job creation and destruction, and two‐period and longer cycles in wages and employment. Long‐term contracts use termination as an incentive device. Underlying the cycles is an intertemporal negative externality. In prescribing a larger (smaller) probability of termination, each current period long‐term contract puts pressure on all next period long‐term contracts to prescribe a smaller (larger) probability of termination, by affecting the tightness of the market for long‐term contracts in the next period.
Analysis of clinical characteristics, prognosis and antibody pathogenicity of pemphigus patients positive for anti‐desmoglein IgG autoantibodies in remission: a retrospective cohort study
Authors: Zhao W.L. , Ishii K. , Egami S. , Xu Z. , Funakoshi T. , Takahashi H. , Tanikawa A. , Ishiko A. , Amagai M. , Yamagami J. 
Published: October 2021

AbstractBackgroundThe detection of serum anti‐desmoglein (Dsg) IgG autoantibodies has been reported to be useful for assessment of disease activity in pemphigus. However, previous studies have reported that anti‐Dsg autoantibodies remain detectable in some patients without active pemphigus lesions.ObjectivesTo investigate the clinical characteristics and antibody pathogenicity of pemphigus patients positive for anti‐Dsg IgG autoantibodies in remission.MethodsWe retrospectively investigated pemphigus patients with a history of clinical remission who visited the Department of Dermatology of Keio University during 2019 and 2020. The antibody pathogenicity was assessed by bead aggregation assay.ResultsWhen patients were recognized as having entered remission (PDAI = 0 and PSL ≦ 10 mg/day for 2 months), serum autoantibodies against Dsg were detected in 72 of 132 patients (54.5%, positive group; PG), but were not detected in 60 patients (45.5%, negative group; NG). Anti‐Dsg antibody titres in remission declined from the active phase in 33 patients in the PG for whom data were available. There were no differences in the chance of reducing PSL to 5 mg/day (P = 0.885) and rate of relapse (P = 0.279) between PG and NG, but fewer patients in PG discontinued corticosteroids (P = 0.004). The ability of patients' sera to block aggregation of Dsg/desmocollin beads was significantly reduced in remission compared to the active phase. However, our results revealed that whole sera in remission still had pathogenic activity in seven of nine patients, and the approximately equal amounts of anti‐Dsg antibodies in active phase and remission showed similar pathogenicity.ConclusionsThis study will provide guidance in cases where autoantibodies are found to be positive in pemphigus patients during remission or steroid reduction.
Adherence to self‐management in patients with multimorbidity and associated factors: A cross‐sectional study in primary health care
Authors: Paukkonen Leila , Oikarinen Anne , Kähkönen Outi , Kyngäs Helvi 
Published: October 2021

AbstractAimThe aim of the study was to explore the adherence to self‐management of patients with multimorbidity, identify associated factors, and determine explanatory factors of their adherence to self‐management in terms of the Theory of Adherence of People with Chronic Disease.BackgroundAdherence to self‐management is essential for successful care of multimorbid patients, but multimorbidity poses challenges for both patients and practitioners due to its care complexity and broad impact on patients’ lives.DesignA cross‐sectional, descriptive exploratory design with the STROBE reporting checklist was applied.MethodsAdult multimorbid patients who attended primary healthcare consultations in Finland were surveyed using self‐administered questionnaires with several instruments including the Adherence of People with Chronic Disease Instrument, Kasari's FIT Index, and Alcohol Use Disorders Identification test. Responses of 124 patients were analysed using descriptive statistics, Spearman correlations, binary logistic regression analysis, and Chi‐squared, or corresponding, tests.ResultsMost patients’ responses indicated good or adequate adherence to care regimens and medications. However, adherence to self‐management for a healthy lifestyle was more frequently inadequate. Adherence was significantly associated with several patient‐related factors, including demographic and health‐related factors, perceived adequacy of loved ones, and patient activation. Significant explanatory factors for adherence included energy and willpower, motivation, results of care, sense of normality, fear of complications and additional diseases, and support from nurses, from physicians, and from family and friends. Various factors were relevant for specific aspects of self‐management.ConclusionsMultimorbid patients’ adherence to self‐management is not an ‘all or none phenomenon, but a multifaceted process with numerous associated and explanatory factors.Relevance to clinical practiceThe findings highlight needs for an individualised whole‐person approach in multimorbid patients’ care to provide the required support for good adherence to self‐management. Healthcare professionals, especially nurses working in primary health care, are well‐positioned to meet this need.
Annual report of the Women's Healthcare Committee, Japan Society of Obstetrics and Gynecology, 2021
Authors: Kato Kiyoko , Terauchi Masakazu 
Published: October 2021

AbstractOur committee was founded in 2010 with the goal of improving women's health. This academic year we focused on the following five activities for the second consecutive year: cooperation between the department of pediatric surgery and the department of obstetrics and gynecology for the treatment of persistent cloaca and Mayer–Rokitansky–Küster–Hauser syndrome in Japan; assessment of the educational training of women's healthcare advisers; increasing screening for breast and cervical cancer; conducting the Nationwide Survey of Prescribing Practices for the Treatment of Menopausal Symptoms; and preventing osteoporosis in survivors of gynecologic cancer. The activities of each subcommittee are detailed below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2021;73(6):684–699).
In vitro ruminal fermentation, methane production and nutrient degradability as affected by fruit and vegetable pomaces in differing concentrations
Authors: Giller Katrin , Bossut Laura , Eggerschwiler Lukas , Terranova Melissa 
Published: October 2021

AbstractPomaces are food industry by‐products and may serve as animal feed to increase sustainability of meat and milk production. The aim of the present study was to evaluate fermentation characteristics of dried fruit and vegetable pomaces in a short‐term in vitro experiment using the Hohenheim Gas Test. A selection of six fruit (apple, aronia, orange, pomegranate, red, white grape) and three vegetable (beetroot, carrot, tomato) pomaces was tested in three concentrations (150, 300, 500 g kg−1 of dry matter (DM)) as supplement to the basal diet (hay, used as control). Three runs were performed, using rumen fluid from one of three different rumen‐cannulated cows in each run. Per run, each compound was tested in duplicate. After 24 h incubation, total gas production, methane and CO2 concentration, short‐chain fatty acids, in vitro organic matter digestibility as well as microbial counts were determined. In addition, the pomaces' polyphenol content including the fractions non‐tannin phenols, condensed tannins and hydrolysable tannins were analysed. Most pomaces did not significantly affect rumen fermentation characteristics in any of the tested dosages and may thus be applied in ruminant nutrition without adverse effects. Aronia significantly decreased (−14.5%) the organic matter digestibility in the highest concentration whereas apple (+12%), carrot (+10%) and beetroot (+8%) increased gas formation related to digestible organic matter. The 500 g kg−1 dosage of pomegranate significantly decreased methane formation by about 28% without impairing digestibility. Pomegranate was the only pomace of those high in total tannins that contained exceptionally high amounts of hydrolysable (90% of total tannins) and proportionally low amounts of condensed tannins (10% of total tannins), indicating that the hydrolysable tannins most likely reduced the methane production. Therefore, pomegranate pomace may be an interesting option for a methane mitigating feed supplement in ruminants and should be considered for following in vivo testing.
Reproductive water supply is prioritized during drought in tomato
Authors: Harrison Day Beatrice L. , Carins‐Murphy Madeline R. , Brodribb Timothy J. 
Published: October 2021

AbstractReproductive success largely defines the fitness of plant species. Understanding how heat and drought affect plant reproduction is thus key to predicting future plant fitness under rising global temperatures. Recent work suggests reproductive tissues are highly vulnerable to water stress in perennial plants where reproductive sacrifice could preserve plant survival. However, most crop species are annuals where such a strategy would theoretically reduce fitness. We examined the reproductive strategy of tomato (Solanum lycopersicum var. Rheinlands Ruhm) to determine whether water supply to fruits is prioritized above vegetative tissues during drought. Using optical methods, we mapped xylem cavitation and tissue shrinkage in vegetative and reproductive organs during dehydration to determine the priority of water flow under acute water stress. Stems and peduncles of tomato showed significantly greater xylem cavitation resistance than leaves. This maintenance of intact water supply enabled tomato fruit to continue to expand during acute water stress, utilizing xylem water made available by tissue collapse and early cavitation of leaves. Here, tomato plants prioritize water supply to reproductive tissues, maintaining fruit development under drought conditions. These results emphasize the critical role of water transport in shaping life history and suggest a broad relevance of hydraulic prioritization in plant ecology.
Management of refractory chylothorax in the neonatal intensive care unit: A 22‐year experience
Authors: Takahashi Yoshiaki , Kinoshita Yoshiaki , Kobayashi Takashi , Arai Yuhki , Ohyama Toshiyuki , Yokota Naoki , Saito Koichi , Sugai Yu , Takano Shoichi 
Published: October 2021

AbstractBackgroundThe aim was to assess the therapeutic strategy of patients with chylothorax in a neonatal intensive care unit.MethodsTwenty‐eight infants with chylothorax were included in this study. Their clinical characteristics and outcomes were reviewed retrospectively.ResultsThe male‐to‐female ratio was 1:1. The mean gestational age and birthweight were 35.1 ± 3.5 weeks and 2,692 ± 791 g, respectively. Eighteen patients were diagnosed with congenital chylothorax; chylothorax occurred postoperatively in 10 patients. Chromosomal anomalies were diagnosed in 8 patients. Six patients received surgical therapy, such as pleurodesis, thoracic duct ligation, or lymphaticovenous anastomosis. Two patients required surgery due to resistance to pleurodesis. In surgically managed patients, the daily maximum amount of pleural effusion (mL)/bodyweight (kg) ratio was significantly larger than in non‐surgically managed patients: 229.0 ± 180.5 versus 59.7 ± 49.2 mL/kg. In the receiver operating characteristic analysis of the daily maximum amount of pleural effusion/bodyweight ratio, the area under the curve was 0.889 when the cut‐off value was 101 mL/kg, and the sensitivity was 0.8333 and the specificity was 0.8095 (P = 0.0059).ConclusionsPleurodesis using OK432 could become a surgical first‐line therapy for chylothorax even for neonates. It was important to initiate pleurodesis for refractory chylothorax at an earlier stage. A daily chylous effusion/bodyweight ratio of >101 mL/kg was a good predictor and seemed to be a useful parameter for prompt surgical intervention.