bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population
Authors: Senda Noriko , Kawaguchi‐Sakita Nobuko , Kawashima Masahiro , Inagaki‐Kawata Yukiko , Yoshida Kenichi , Takada Masahiro , Kataoka Masako , Torii Masae , Nishimura Tomomi , Kawaguchi Kosuke , Suzuki Eiji , Kataoka Yuki , Matsumoto Yoshiaki , Yoshibayashi Hiroshi , Yamagami Kazuhiko , Tsuyuki Shigeru , Takahara Sachiko , Yamauchi Akira , Shinkura Nobuhiko , Kato Hironori , Moriguchi Yoshio , Okamura Ryuji , Kan Norimichi , Suwa Hirofumi , Sakata Shingo , Mashima Susumu , Yotsumoto Fumiaki , Tachibana Tsuyoshi , Tanaka Mitsuru , Togashi Kaori , Haga Hironori , Yamada Takahiro , Kosugi Shinji , Inamoto Takashi , Sugimoto Masahiro , Ogawa Seishi , Toi Masakazu 
Published: May 2021

AbstractPredicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer‐Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target‐capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third‐degree relatives), triple‐negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69‐0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high‐risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction.
A chaotic grey wolf optimizer for constrained optimization problems
Authors: Rodrigues Leonardo Ramos 
Published: May 2021

AbstractBio‐inspired algorithms have become popular due to their capability of finding good solutions for complex optimization problems in an acceptable computational time. The Grey Wolf Optimizer is a nature‐inspired, population‐based metaheuristic that simulates the social hierarchy and the hunting strategy observed in a grey wolf pack. Although the Grey Wolf Optimizer has been successfully applied to solve different optimization problems, it may suffer from premature convergence and get stuck in local optima. In order to overcome these drawbacks, this paper proposes a chaotic version of the Grey Wolf Optimizer that differs from the original algorithm and previously published modified versions because it does not add a chaotic variable in the parameters that control the execution of the algorithm. Instead, the proposed model uses a chaotic variable to define the wolves in the pack that will be used to guide the hunting process in each iteration of the algorithm. Numerical experiments using 20 benchmark functions are carried out. The performance of the proposed model is compared with the performance of the original Grey Wolf Optimizer and other well‐known algorithms, namely the Particle Swarm Optimization, the Genetic Algorithm, the Symbiotic Organisms Search, and the Teaching‐Learning Based Optimization. Nine chaotic maps reported in the literature are tested. The results show that the proposed algorithm has a very competitive performance, and the Chebyshev map presented the best performance among the chaotic maps simulated. The proposed algorithm can be integrated into other modified versions of the Grey Wolf Optimizer in a straightforward way.
The Alliance–Outcome Association in Couple Therapy: A Common Fate Model
Authors: Quirk Kelley , Drinane Joanna M. , Edelman Anna , Chow Daryl , Lim Joline , Chandra Diana , Miller Scott , Owen Jesse 
Published: May 2021

AbstractThe working alliance has been shown to be a robust predictor of couple therapy outcomes. However, there are still questions regarding the best way to conceptualize and analyze the association between the alliance and outcomes in the couple therapy context. This study presents results from a relatively novel analytic approach for evaluating the alliance and therapy outcomes via the shared influence model (i.e., common fate statistical methodology) with 93 couples who had at least three sessions. Examining the alliance in couple therapy this way allows for nuance in conceptualizing the process of the alliance among partners and the therapist in couple therapy. Empirically, the question that remains is whether the shared experience of the alliance between partners is a stronger predictor of therapy outcome as compared to the unique individual experiences of the alliance. This approach has not yet been utilized to model the couple alliance–outcome association. Results revealed that the shared influence model demonstrated a significant association between the alliance and therapy outcome. Specifically, the couple‐level alliance construct was adequately represented from the partners’ alliance ratings with the therapist, and couples that report higher shared alliance experiences were also likely to have better therapy outcomes. These findings suggest that conceptualizing and analyzing the alliance at the couple level may be strongly advantageous. Implications for research and practice are provided.
Identification of microRNA‐96‐5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma
Authors: Matsui Takeshi , Hamada‐Tsutsumi Susumu , Naito Yutaka , Nojima Masanori , Iio Etsuko , Tamori Akihiro , Kubo Shoji , Ide Tatsuya , Kondo Yasuteru , Eguchi Yuichiro , Komori Atsumasa , Morine Yuji , Shimada Mitsuo , Utsunomiya Tohru , Shirabe Ken , Kimura Koichi , Hiasa Yoichi , Chuaypen Natthaya , Tangkijvanich Pisit , Naiki‐Ito Aya , Takahashi Satoru , Ochiya Takahiro , Tanaka Yasuhito 
Published: May 2021

AbstractAimThe microRNA (miR) clusters miR‐183/96/182 and miR‐217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC‐HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC‐HCC and analyze the antitumor effects of miR‐96‐5p.MethodsThe association between recurrence‐free survival of 111 NBNC‐HCC patients and the levels of miR‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, miR‐216a‐5p, and miR‐216b‐5p in tumor and adjacent tissues was investigated. The impact of miR‐96‐5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively.ResultsMicroRNA‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, and miR‐216b‐5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR‐182‐5p (p = 0.007) and miR‐217‐5p (p = 0.008) were associated with poor recurrence‐free survival. In contrast, a low tumor/adjacent ratio of miR‐96‐5p (p < 0.001) was associated with poor recurrence‐free survival. It suggested that further upregulation of miR‐96‐5p in tumors might have an inhibitory effect on recurrence. Transfection of miR‐96‐5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA‐96‐5p also suppressed proliferation and invasion, which inhibited epithelial‐to‐mesenchymal transition of HCC cells.ConclusionMicroRNA‐96‐5p as a tumor suppressor would be valuable to stratify NBNC‐HCC patients at high risk of recurrence.
Systemic and mucosal mobilization of granulocyte subsets during lentiviral infection
Authors: Jones Rhianna , Manickam Cordelia , Ram Daniel R. , Kroll Kyle , Hueber Brady , Woolley Griffin , Shah Spandan V. , Smith Scott , Varner Valerie , Reeves R. Keith 
Published: May 2021

AbstractGranulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver and whole blood from experimentally naïve and chronically SHIVsf162p3‐infected RM were analysed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils—CD45+ CD66+ CD49d+; neutrophils—CD45+ CD66+ CD14+; and basophils—CD45+ CD123+ FcRε+. Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged from 25·4% to 81·5% neutrophils, 0·59% to 13·3% eosinophils and 0·059% to 1·8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils and colorectal eosinophils were all observed in chronic lentiviral disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils and vaginal eosinophils of SHIVsf162p3‐infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentiviral infection, most notably in the gastrointestinal mucosae where a significant inflammation and disruption occurs in lentivirus‐induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention.
In‐Situ Displacement: Institutional Practices and the Making of the Hindu Other
Authors: Feldman Shelley 
Published: May 2021

AbstractThis paper introduces the concept of in‐situ displacement‐displacement without mobility‐as an analytic for understanding the place of Hindus in Muslim majority East Bengal, East Pakistan, and Bangladesh, a national formation that is best defined as one of a changing identification with Pakistan and India, and, subsequently, as a sovereign country in South Asia. Elaborating the contributions of Corrigan and Sayer on state formation and law, the paper highlights the importance of the judiciary as constitutive of the meanings that attend to belonging in the body politic. Evidence for this argument comes from court cases in the Dacca Law Review.
Clinical benefits of TNF‐α inhibitors in Chinese adult patients with NLRP3‐associated autoinflammatory disease
Authors: Wu N. , Wu D. , Zhao M. , Miao J. , Yu W. , Wang Y. , Shen M. 
Published: May 2021

AbstractBackgroundNucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3)‐associated autoinflammatory disease (NLRP3‐AID) is a rare, heterogeneous disease entity associated with mutations in NLRP3. Biologic therapy for NLRP3‐AID yields diverse results.ObjectivesWe aimed to evaluate the clinical features and outcomes of Chinese adult patients with NLRP3‐AID who were treated with tumour necrosis factor (TNF)‐α inhibitors.MethodsFive patients with NLRP3‐AID were diagnosed and treated with TNF‐α inhibitors at Peking Union Medical College Hospital between 2017 and 2020 and were followed up for 6 to 12 months. All patients were systematically studied for treatment outcomes, including clinical manifestations and inflammatory markers.ResultsAll five adult NLRP3‐AID patients were Chinese Han, and four patients were males. The mean age at disease onset was 4.2 ± 4.1 years, and the mean time of diagnosis delay was 19.8 ± 6 years. All patients received TNF‐α inhibitors with or without methotrexate/prednisone. During follow‐up, all patients achieved remarkable clinical remission of skin lesions and polyarthritis and showed improvements in acute‐phase reactants, inflammatory cytokines, patient visual analogue scale, physician global assessment and 36‐item Short Form (SF‐36).ConclusionsEarly diagnosis and effective therapy for NLRP3‐AID are essential for avoiding irreversible organ damage. TNF‐α inhibitors might serve as a therapeutic alternative for patients with NLRP3‐AID who have unsatisfactory responses or no access to interleukin‐1 inhibitors.
Community use of paracetamol and ibuprofen in children with fever
Authors: Kloeden Bethany , Tham Doris , Oakley Ed , Cheek John 
Published: May 2021

ObjectiveTo establish, in children aged from 3 months to less than 13 years with a febrile illness, caregiver medication usage patterns and drivers. Secondary objectives assessed caregiver knowledge and concern about fever.MethodologyThis was a prospective, observational study of a convenience sample of 147 children presenting to a tertiary Paediatric Emergency Department, where the caregivers reported a concern of fever within the preceding 48 h. A paper‐based survey was completed by the caregivers, and the results analysed both qualitatively and quantitatively.ResultsCaregivers of 92.4% had administered medication for fever in the 48 h prior to presentation. Dual therapy of paracetamol and ibuprofen was used by 45.8%, with paracetamol used more frequently as monotherapy (35.4%). Almost one‐third of caregivers woke their child to administer medication. Just over one‐third of respondents stated that a temperature of less than 38.0°C is a fever. The majority of caregivers (67.6%) said that fever is bad for their child, with 97.9% being concerned by fever. Almost half the children (46.8%) were given medication purely to treat the degree of the temperature. General practitioners were reported as the strongest influence on medication decision (60%).ConclusionsThis study provides insight into current knowledge and practices of parents regarding fever and its treatment. The results of this study may be used to direct future interventions to educate caregivers on this topic.
Current Australian clinical practice in use of botulinum toxin‐A to manage paediatric hypertonicity
Authors: O'Flaherty Stephen J , Stewart Kirsty 
Published: May 2021

AimTo describe current rehabilitation paediatricians' use of intramuscular botulinum toxin‐A (BoNT‐A) to manage hypertonicity.MethodsCross‐sectional survey.ResultsIn late 2019, 32 of the 35 identified Australian rehabilitation paediatricians who use BoNT‐A to manage paediatric hypertonicity completed the survey. Annually, they administer just over 3750 courses of BoNT‐A to manage hypertonicity with a mean of 11 years of clinical experience. Sedation was used by all but 1 clinician who used a number of other strategies during the procedure. Mean (and median) maximum dose of OnabotulinumtoxinA (Botox) was 400 Units (range 300–450 Units). Only three clinicians indicated that they used AbobotulinumtoxinA (Dysport) – the other BoNT‐A preparation approved for children available in Australia; analysis of its use was not performed. Dose modifications were made by clinicians according to a patient's response to a previous course of BoNT‐A (88% of respondents); patient experience of a previous adverse event (78%); history of aspiration or dysphagia (65 and 63%, respectively); and the presence of dystonia; and where the patient was GMFCS level V (53% each). Intervals between courses ranged from 3 to 24 months with the variation due to clinical circumstances.ConclusionClinical practice in BoNT‐A management of paediatric hypertonicity was largely consistent in regard to maximum doses of OnabotulinumtoxinA (Botox) used. Dose modification and time between injection courses varied according to individual clinical presentation. Procedural sedation was used extensively.
Evaluation of training, patient and practitioner perspectives on community‐based monitoring of patients with stable age‐related macular degeneration compared to hospital‐based care: The FENETRE study report no. 1
Authors: Read Simon , Lawrenson John G , Harper Robert A , Hanley Thomas , Balaskas Konstantinos , Waterman Heather 
Published: May 2021

AbstractPurposeDescribe the development, delivery, acceptability and evaluation of a modular training programme for community‐based, non‐medical practitioners monitoring patients with quiescent neovascular age related macular degeneration (QnAMD). Also, report on a qualitative process evaluation conducted during the pilot phase of a randomised control trial (the FENETRE Study) exploring patient and practitioner acceptability of community‐based QnAMD care relative to hospital‐based care.MethodsLearning outcomes from The College of Optometrists’ Medical Retina higher qualifications and the Royal College of Ophthalmologists’ Common Clinical Competency Framework were used to develop a competency framework for QnAMD care. Training was delivered online, comprising six asynchronous lectures followed by two synchronous case‐based discussion webinars, with an accredited assessment of 24 case vignettes. An anonymous evaluation survey was conducted with the first two FENETRE cohorts (n = 38). Separately, we undertook a qualitative process evaluation, sampling purposively in four hospitals and five community‐based practices, interviewing nine patients and eight practitioners.ResultsSurvey responses (n = 26) showed community optometrists were very satisfied (n = 12; 46%) or satisfied (n = 14; 54%) with the training; feedback reflected by qualitative process evaluation data. Overall, optometrists also felt either confident (n = 15; 58%) or very confident (n = 8; 31%) in conducting AMD monitoring appointments following training, a finding also corroborated by interview data from optometrists participating in the initial pilot phase roll‐out. Optometrists identified patient convenience and alleviating pressures in hospital care as the primary reasons for acceptability of community pathways. Data from patients entering community practices suggested they largely found this at least as safe and convenient as hospital care, although some patients randomised to hospital care perceived that as safer.ConclusionThis pilot study has shown the development and implementation of a collaborative community monitoring model is feasible, with satisfaction from community optometrists for training and accreditation, and broad acceptance for the pathway by both patients and practitioners.
The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function
Authors: Jones Danial T. , Macdonald Jamie H. , Sandoo Aamer , Oliver Samuel J. , Rossetti Gabriella M. K. 
Published: May 2021

New Findings
What is the central question of this study?
The aim was primarily to determine the effect of hypoxia on microvascular function and secondarily whether superior cardiorespiratory fitness is protective against hypoxia‐induced impairment in vascular function.
What is the main finding and its importance?
Hypoxia reduced endothelium‐dependent but not endothelium‐independent microvascular function. The extent of impairment was twofold higher in the microcirculation compared with the large blood vessels. This study suggests that individuals with superior cardiorespiratory fitness might preserve microvascular function in hypoxia. These findings highlight the sensitivity of the microvascular circulation to hypoxia.

AbstractHypoxia is associated with diminished bioavailability of the endothelium‐derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia‐induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty‐nine healthy adults [24 (SD = 4 ) years of age] completed normoxic and hypoxic [inspired O2 fraction = 0.209] trials in this double‐blinded, counterbalanced crossover study. After 30 min, we assessed the laser Doppler imaging‐determined perfusion response to iontophoresis of ACh as a measure of endothelium‐dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium‐independent microvascular function. After 60 min, we assessed brachial flow‐mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium‐dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆) = −109% {interquartile range: 542.7}, P < 0.05), but not endothelium‐independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow‐mediated dilatation compared with normoxia ( [95% CI = −1.80, −0.58 (Confidence Intervals)]%, P < 0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r = 0.45, P = 0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium‐dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.
Optimization Design of an Efficient Evacuator for Gun Barrels
Authors: Sun Quanzhao , Chen Li , Zhang Jie , Song Yanming , Yang Guolai , Lu Baochun 
Published: May 2021

Abstract
Evacuators are key components of gun barrels, and their main function is to drain the gunpowder gas remaining in the gun bore from the muzzle by ejection. To design an efficient evacuator for the gun barrels, an optimization model with the mathematical expressions describing the working process of the evacuator was established. The four structural parameters that affect the efficiency of the evacuator, including the volume of the gas storage cylinder chamber, the distance of the nozzle from the muzzle end face, the cross-sectional area of the nozzles and the cross-sectional area of the valves, were optimized. The effective working time and reliability indicator of the optimized evacuator were improved. This work describes a framework for improving the design of highly efficient evacuators on gun barrels.
A unique archetype of conservation in Himachal Pradesh, western Himalaya, India
Authors: Sharma Rupali , Sharma Monika , Mathela Manisha , Bargali Himanshu , Kumar Amit 
Published: May 2021

Owing to numerous emerging threats to biodiversity, its conservation has been of paramount importance in today’s world. Interestingly, many modern practices have been followed globally for the conservation of natural resources, yet traditional conservation practices that could set an excellent example need to be explored worldwide. Keeping this in view, the current communication aims to highlight a unique conservation method that has been practiced in the remote and cold-arid region of the state of Himachal Pradesh in the western Himalaya. Locally known as ‘Praja Mandal’, this indigenous system of conservation needs to be addressed and adopted nationwide with an eye towards a sustainable ecosystem.