bluuebunny/crossref_metadata_2025 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

Predicting 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

Bio‐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

The 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.
Cancer cell metabolism connects epigenetic modifications to transcriptional regulation
Authors: Morrison Ashby J.
Published: May 2021

Adaptation of cellular function with the nutrient environment is essential for survival. Failure to adapt can lead to cell death and/or disease. Indeed, energy metabolism alterations are a major contributing factor for many pathologies, including cancer, cardiovascular disease, and diabetes. In particular, a primary characteristic of cancer cells is altered metabolism that promotes survival and proliferation even in the presence of limited nutrients. Interestingly, recent studies demonstrate that metabolic pathways produce intermediary metabolites that directly influence epigenetic modifications in the genome. Emerging evidence demonstrates that metabolic processes in cancer cells fuel malignant growth, in part, through epigenetic regulation of gene expression programs important for proliferation and adaptive survival. In this review, recent progress toward understanding the relationship of cancer cell metabolism, epigenetic modification, and transcriptional regulation will be discussed. Specifically, the need for adaptive cell metabolism and its modulation in cancer cells will be introduced. Current knowledge on the emerging field of metabolite production and epigenetic modification will also be reviewed. Alterations of DNA (de)methylation, histone modifications, such as (de)methylation and (de)acylation, as well as chromatin remodeling, will be discussed in the context of cancer cell metabolism. Finally, how these epigenetic alterations contribute to cancer cell phenotypes will be summarized. Collectively, these studies reveal that both metabolic and epigenetic pathways in cancer cells are closely linked, representing multiple opportunities to therapeutically target the unique features of malignant growth.
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

Aim

The 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.

Methods

The 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.

Results

MicroRNA‐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.

Conclusion

MicroRNA‐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

Granulocytes 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

This 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

Background

Nucleotide‐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.

Objectives

We 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.

Methods

Five 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.

Results

All 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).

Conclusions

Early 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

Objective

To 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.

Methodology

This 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.

Results

Caregivers 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%).

Conclusions

This 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

Aim

To describe current rehabilitation paediatricians' use of intramuscular botulinum toxin‐A (BoNT‐A) to manage hypertonicity.

Methods

Cross‐sectional survey.

Results

In 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.

Conclusion

Clinical 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

Purpose

Describe 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.

Methods

Learning 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.

Results

Survey 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.

Conclusion

This 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.
Corrigendum: On the cuspidal cohomology of S-arithmetic subgroups of reductive groups over number fields
Authors: Labesse Jean-Pierre , Schwermer Joachim
Published: May 2021

The aim of this corrigendum is to correct an error in Corollary 10.7 to Theorem 10.6, one of the main results in the paper ‘On the cuspidal cohomology of $S$-arithmetic subgroups of reductive groups over number fields’. This makes necessary a thorough investigation of the conditions under which a Cartan-type automorphism exists on $G_1=\mathrm {Res}_{\mathbb {C}/\mathbb {R}}G_0$, where $G_0$ is a connected semisimple algebraic group defined over $\mathbb {R}$.
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.

Hypoxia 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

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.
Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth
Authors: Li Fei , Du Xufei , Lan Fen , Li Na , Zhang Chao , Zhu Chen , Wang Xiaohui , He Yicheng , Shao Zhehua , Chen Haixia , Luo Man , Li Wen , Chen Zhihua , Ying Songmin , Shen Huahao
Published: May 2021

Eosinophils primarily secrete CCL6 to promote tumor cell migration and metastasis formation.
Deep exploration of random forest model boosts the interpretability of machine learning studies of complicated immune responses and lung burden of nanoparticles
Authors: Yu Fubo , Wei Changhong , Deng Peng , Peng Ting , Hu Xiangang
Published: May 2021

A proposed machine learning method capable of mining feature interactions reveals the mechanisms of bio-nano interactions.
BRD4 methylation by the methyltransferase SETD6 regulates selective transcription to control mRNA translation
Authors: Vershinin Zlata , Feldman Michal , Werner Thilo , Weil Lital Estrella , Kublanovsky Margarita , Abaev-Schneiderman Elina , Sklarz Menachem , Lam Enid Y. N. , Alasad Khawla , Picaud Sarah , Rotblat Barak , McAdam Ruth A. , Chalifa-Caspi Vered , Bantscheff Marcus , Chapman Trevor , Lewis Huw D. , Filippakopoulos Panagis , Dawson Mark A. , Grandi Paola , Prinjha Rab K. , Levy Dan
Published: May 2021

Lysine methylation of BRD4 selectively determines the recruitment of E2F1 to specific target genes to regulate mRNA translation.
A hindbrain dopaminergic neural circuit prevents weight gain by reinforcing food satiation
Authors: Han Yong , Xia Guobin , He Yanlin , He Yang , Farias Monica , Xu Yong , Wu Qi
Published: May 2021

A dopaminergic neural circuit projecting from the VTA to the hindbrain regulates feeding by transducing meal satiation signals.
Plaque assay of neonatal calf diarrhea virus and the neutralizing antibody in human sera
Authors: Matsuno S , Inouye S , Kono R
Published: May 2021

Neonatal calf diarrhea virus (a bovine rotavirus) formed distinct plaques in monolayers of MA-104 cells, an established macacus rhesus monkey kidney cell line, when diethylaminoethyl dextran and trypsin were included in the overlay medium. By using this plaque assay method, titration of neutralizing antibody to neonatal calf diarrhea virus was made feasible. It was demonstrated that some human sera contained neutralizing antibody to this agent.
Antibodies to hepatitis A virus: patterns by two procedures
Authors: Rakela J , Stevenson D , Edwards V M , Gordon I , Mosley J W
Published: May 2021

Antibody to hepatitis A virus demonstrable by immune electron microscopy appeared early but remained at low levels for several weeks. Antibody detectable by immune adherence hemagglutination was delayed.
Field evaluation of New York City medium in the biological environment-CO2 chamber in recovery of Neisseria gonorrhoeae and urogenital mycoplasmas
Authors: Faur Y C , Weisburd M H , Wilson M E , May P S
Published: May 2021

The biological environment-CO2 chamber containing New York City (NYC) medium was evaluated in a clinical field trial in comparison with Transgrow and NYC medium in plates for the recovery of Neisseria gonorrhoeae and with NYC medium for urogenital mycoplasmas. The results of the study indicated that the biological environment chamber-CO2 culturing system with NYC medium is an effective method for the handling, transport, and culture of N. gonorrhoeae, large-colony mycoplasmas, and T-mycoplasmas if the delay in transport and incubation does not exceed 24 h.
Characterization and identification of gram-negative, nonfermentative bacteria
Authors: Oberhofer T R , Rowen J W , Cunningham G F
Published: May 2021

The morphological and physiological characteristics of 593 strains of nonfermentative, gram-negative bacteria are described. A battery of 46 tests was used to identify and differentiate strains representing 8 genera and 31 species of named and group-designated bacteria. Seven selected amides and organic salts were closely examined to determine their usefulness, individually or as a battery, in characterizing and identifying the organisms. Of these, allantoin and acetamide showed the most promise in differentiating the more commonly occurring organisms from biochemically similar species. Susceptiblilty patterns to 12 antimicrobics also proved useful in differentiation, especially among atypical strains.
Yersinia enterocolitica: recovery and characterization of two unusual isolates from a case of acute enteritis
Authors: Bottone E J , Robin T
Published: May 2021

Enteritis caused by Yersinia enterocolitica appears to be an uncommon occurrence in the United States. Most of the reported cases have been caused by biochemically typical Y. enterocolitica serotype O:8, the most frequently encountered serotype in the United States. The present report describes the isolation of two biochemically and serologically unusual Y. enterocolitica isolates from a patient with acute enteritis. One strain was distinguished by the rapid fermentation of rhamnose and raffinose and by citrate utilization at 22 degrees C but not at 37 degrees C. The other isolate was sucrose negative, and at either temperature it lacked both the fermentative capability for rhamnose and raffinose and the ability to utilize sodium citrate. Neither strain was agglutinable with known Y. enterocolitica antisera. The rhamnose-positive isolate showed an increased resistance to ampicillin, cephalothin, colymycin, and penicillin when tested at 22 degrees C as compared to results obtained at 37 degrees C. The demonstration that one patient's serum contained agglutinins (1:64) against the sucrose-negative strain supports its etiological significance. The role of the rhamnose-positive strain in the patient's illness is speculative. It conceivably could have potentiated the pathogenicity of the sucrose-negative isolate.
Simplified media for isolating Neisseria gonorrhoeae
Authors: Sng E H , Rajan V S , Lim A L
Published: May 2021

Two simplified media for isolating Neisseria gonorrhoeae are described. They differ from the modified Thayer-Martin medium in the enrichment and antibiotics used for preparation. The enrichment for one, enrichment 4 medium, contains only four ingredients, and amphotericin B is used instead of nystatin. This medium is comparable to the modified Thayer-Martin medium for isolating N.gonorrhoeae. It is convenient to prepare and is only one-third the cost of Thayer Martin medium. It is a suitable alternative to the modified Thayer-Martin. The enrichment 5 medium is a hemoglobin-free version of enrichment 4 medium. It is somewhat more selective for contaminants but is also more inhibitory for N. gonorrhoeae.
Effects of Gaseous CO2 and bicarbonate on the growth of Neisseria gonorrhoeae
Authors: Jones R T , Talley R S
Published: May 2021

The quantitative and qualitative growth response of Neisseria gonorrhoeae strains was assessed under the following conditions: incubation in a candle jar (approximately 2.5% ambient CO2) on medium without bicarbonate, incubation in air on medium without bicarbonate, incubation in air on medium with bicarbonate, and incubation in air in a sealed jar on medium with bicarbonate. Incubation in the presence of ambient CO2 (candle jar) resulted in the highest plating efficiencies for the three laboratory strains 9, 62, and 2686. The addition of NaHCO3 to the medium enhanced the growth response in air of all three strains, particularly if incubation was carried out in a closed environment (sealed jar). The qualitative growth response of 34 clinical isolates and laboratory strains was assessed under the same conditions of incubation after the plating of an inoculum containing approximately 2 X 10(6) bacteria. The strains were divided into different classes based on their growth responses. About 40% of the strains grew as well on bicarbonate-containing medium incubated in air in sealed jars as they did on medium without bicarbonate incubated in a candle jar. Ten percent of the strains showed only slight growth on bicarbonate containing medium incubated in sealed jars and appeared to have an almost obligate requirement for ambient CO2. Twenty percent of the strains apparently had partially lost their requirement for gaseous C02 and showed slight growth in air on medium without bicarbonate and slight to moderate growth in air on medium containing NaHCO3.The remaining 30% seemed to have completely lost their requirement for gaseous C02 and/or the bicarbonate anion and grew almost as well in air on medium without bicarbonate as they did in either ambient C02 (candle jar) or on medium containing bicarbonate incubated in a sealed jar. These results suggest that N. gonorrhoeae strains may vary widely in their requirements for CO2 and/or the HCO3-anion. Incubation in the presence of ambient CO2 tends to maximize the growth response on solid medium of those strains, which require it for growth. The presence of ambient CO2 is particularly important if growth is to be obtained after the plating of small inocula. Medium conatining 0.1% NaHCO3, if incubated in a closed environment (sealed jar), apperas to be equivalent to medium without bicarbonate incubated in ambient CO2 in supporting the growth of some but not all strains of N. gonorrhoeae.
Detection of candida serum precipitins by counterimmunoelectrophoresis: an adjunct in determining significant candidiasis
Authors: Dee T H , Rytel M W
Published: May 2021

We report our experience with the use of counterimmunoelectrophoresis for the detection and quantitation of candida serum precipitins in 164 patients. Group I consisted of 24 patients with significant candidiasis; group II consisted of 97 patients with either colonization or transient candidemia; and group III consisted of 43 subjects with noncandida systemic mycoses, bacterial infections, and normal controls. Prospective studies were done in ten patients. Double immunodiffusion was performed in all cases. Ratios of counterimmunoelectrophoresis precipitin detection were significantly different between groups I and II and groups I and III (P less than 0.001). Precipitin titers of 1:8 or greater were found more often in group I as compared to group II or III (P less than 0.001). All prospectively studied patients who developed significant candidiasis had peak precipitin titers of greater than or equal to 1:8(greater than fourfold titer increase) during the period of observation. Quantitation of candida serum precipitins by counterimmunoelectrophoresis is helpful in diagnosing significant candidiasis.
New differential medium for the isolation of Corynebacterium vaginale
Authors: Mickelsen P A , McCarthy L R , Mangum M E
Published: May 2021

A new differential medium for isolation of Corynebacterium vaginale is described. This opaque medium containing 1% corn starch allows detection of C. vaginale by the zones of clearing developing around the colonies.
Comparative evaluation of three different commercial blood culture media for recovery of anaerobic organisms
Authors: Mangels J I , Lindberg L H , Vosti K L
Published: May 2021

A comparison of three different commercial media was made to assess their recovery of anaerobic organisms from the blood stream. The three media used were the 50-ml brain heart infusion broth with added CO2 (Pfizer), the 50-ml Thiol broth with added CO2 (Difco), and the 50-ml prereduced, supplemented peptone broth in a Vacutainer tube with added CO2 (Becton-Dickinson). During a period of 17 consecutive months, 12,216 specimens of blood were processed with each broth. Aerobic or anaerobic bacteria were recovered from 913 specimens (7%). Seventy-four specimens (8%) of the total positive cultures contained anaerobic organisms. When potential contaminants were removed from the totals, 7% of the positive cultures contained anaerobic organisms and 7% of the patients with positive cultures had bacteremia with anaerobic bacteria. Of the three commercial blood culture media studied, the prereduced, supplemented peptone broth recovered more anaerobic organisms than did either the brain heart infusion or Thiol broths.
Serodiagnosis of viral hepatitis A: detection of acute-phase immunoglobulin M anti-hepatitis A virus by radioimmunoassay
Authors: Bradley D W , Maynard J E , Hindman S H , Hornbeck C L , Fields H A , McCaustland K A , Cook E H
Published: May 2021

A modified micro solid-phase radioimmunoassay (RIA) for antibody to hepatitis A virus (anti-HAV) was developed. This double antibody procedure was performed by coating the surface of a polyvinyl microtiter plate "well" with 200 microliter of a 1:1,000 dilution of a patient's test serum. Purified HAV and 125I-labeled immunoglobulin G (IgG) anti-HAV were then sequentially added to form an antibody sandwich. The specificity and sensitivity of the RIA procedure for anti-HAV were verified by examination of coded human and chimpanzee serum specimens. Radioimmunoassay of early-acute-phase serum specimens from human cases of hepatitis A revealed the presence of anti-HAV activity. Differential examination by RIA of IgG and IgM fractions of acute-phase sera from experimentally infected chimpanzees demonstrated that IgM contained the bulk of the anti-HAV activity. A modification of the RIA procedure for anti-HAV (RIA-IgM blocking), incorporating an incubation step with anti-IgM (Mu chain specific), was further shown to differentiate acute- from convalescent-phase hepatitis A sera. This adapted RIA-IgM blocking procedure required less than 1 microliter of a single acute-phase serum specimen for the diagnosis of viral hepatitis A.
Syphla-Chek: a qualitative study
Authors: Dziuk P E , Black D A , Therrell B L
Published: May 2021

A qualitative evaluation of the newly marketed Syphla-Chek Test (Hyland, Div. of Travenol Laboratories, Inc., Costa Mesa, Calif.), a macroscopically read, nontreponemal card test, was undertaken in order to further evaluate the validity of this procedure as an aid in the diagnosis of syphilis. A total of 1,074 randomly selected sera submitted to the Texas Department of Health Resources for routine analysis, for confirmational analysis, and as a result of problems in analysis, were examined using the Venereal Disease Research Laboratory (VDRL) slide test, the Rapid Plasma Reagin (circle) Card Test (RPRCT), Syphla-Chek Test, and the fluorescent treponemal antibody absorption (FTA-ABS) test. Comparison of the reagin testing procedures studied versus the FTA-ABS procedure led to the following order of agreement with FTA-ABS reactive results: Syphla-Chek, 88.8%; RPRCT, 87.1%; and VDRL, 83.2%. Agreement with FTA-ABS nonreactive results was in order: RPRCT, 86.7%; Syphla-Chek, 79.6%; and VDRL, 78.7%. The relatively few minor procedural problems encountered with the Syphla-Chek Test during this study are also discussed.
Vibrio alginolyticus infections in Hawaii
Authors: Pien F , Lee K , Higa H
Published: May 2021

Clinical and bacteriological features of eight cases of Vibrio alginolyticus infections in Hawaii are presented. These isolates occurred in superficial sites, primarily related to infections caused by swimming.
Delayed manifestation of extensive COVID-19-associated coagulopathy in high-risk patient
Authors: Sharma Purva , Chakraborty Kanishka
Published: May 2021

COVID-19 is an infectious disease caused by the novel coronavirus. It presents as an acute respiratory illness, however, it also affects multiple other organ systems. One such unique manifestation is systemic coagulopathy involving arterial and venous systems. We present a 29-year-old woman with Hodgkin’s lymphoma, who was diagnosed with COVID-19 infection prior to initiating chemotherapy. Two months after resolution of symptoms and testing negative for COVID-19, she presented with multiple acute thromboembolic complications of the infection, including bilateral jugular venous thrombosis, right atrial clot and arterial emboli in the brain resulting in cerebrovascular injury. These were thought to be delayed manifestations of the systemic coagulopathy secondary to infection. Also, some of these thromboembolic phenomena occurred while the patient was on anticoagulation, which emphasises the extensive hyperinflammatory state caused by the virus. This case highlights the importance of thromboprophylaxis especially in high-risk patients with this infection.
Quality indicators for knee and hip osteoarthritis care: a systematic review
Authors: Arslan Ilgin G , Rozendaal Rianne M , van Middelkoop Marienke , Stitzinger Saskia A G , Van de Kerkhove Maarten-Paul , Voorbrood Vincent M I , Bindels Patrick J E , Bierma-Zeinstra Sita M A , Schiphof Dieuwke
Published: May 2021

To provide an overview of quality indicators (QIs) for knee and hip osteoarthritis (KHOA) care and to highlight differences in healthcare settings. A database search was conducted in MEDLINE (PubMed), EMBASE, CINAHL, Web of Science, Cochrane CENTRAL and Google Scholar, OpenGrey and Prospective Trial Register, up to March 2020. Studies developing or adapting existing QI(s) for patients with osteoarthritis were eligible for inclusion. Included studies were categorised into healthcare settings. QIs from included studies were categorised into structure, process and outcome of care. Within these categories, QIs were grouped into themes (eg, physical therapy). A narrative synthesis was used to describe differences and similarities between healthcare settings. We included 20 studies with a total of 196 QIs mostly related to the process of care in different healthcare settings. Few studies included patients’ perspectives. Rigorous methods for evidence synthesis to develop QIs were rarely used. Narrative analysis showed differences in QIs between healthcare settings with regard to exercise therapy, weight counselling, referral to laboratory tests and ‘do not do’ QIs. Differences within the same healthcare setting were identified on radiographic assessment. The heterogeneity in QIs emphasise the necessity to carefully select QIs for KHOA depending on the healthcare setting. This review provides an overview of QIs outlined to their healthcare settings to support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of KHOA care. We strongly recommend to review QIs against the most recent guidelines before implementing them into practice.
MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2
Authors: Wang Hong , Wang Shuqin , Huang Shanshan
Published: May 2021

Acute lung injury (ALI) is a severe respiratory disorder with a high rate of mortality, and is characterized by excessive cell apoptosis and inflammation. MicroRNAs (miRNAs) play pivotal roles in ALI. This study examined the biological function of miR-494-3p in cell apoptosis and inflammatory response in ALI. For this, mice were injected with lipopolysaccharide (LPS) to generate an in-vivo model of ALI (ALI mice), and WI-38 cells were stimulated with lipopolysaccharide (LPS) to generate an in-vitro model of ALI. We found that miR-494-3p was significantly downregulated in the ALI mice and in the in-vitro model. Overexpression of miR-494-3p inhibited inflammation and cell apoptosis in the LPS-induced WI-38 cells, and improved the symptoms of lung injury in the ALI mice. We then identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a novel target of miR-494-3p in the WI-38 cells. Furthermore, miR-494-3p suppressed cell apoptosis and the inflammatory response in LPS-treated WI-38 cells through targeting CMPK2. The NLRP3 inflammasome is reportedly responsible for the activation of inflammatory processes. In our study, CMPK2 was confirmed to activate the NLRP3 inflammasome in LPS-treated WI-38 cells. In conclusion, miR-494-3p attenuates ALI through inhibiting cell apoptosis and the inflammatory response by targeting CMPK2, which suggests the value of miR-494-3p as a target for the treatment for ALI.
Graph-based Multimodal Ranking Models for Multimodal Summarization
Authors: Zhu Junnan , Xiang Lu , Zhou Yu , Zhang Jiajun , Zong Chengqing
Published: May 2021

Multimodal summarization aims to extract the most important information from the multimedia input. It is becoming increasingly popular due to the rapid growth of multimedia data in recent years. There are various researches focusing on different multimodal summarization tasks. However, the existing methods can only generate single-modal output or multimodal output. In addition, most of them need a lot of annotated samples for training, which makes it difficult to be generalized to other tasks or domains. Motivated by this, we propose a unified framework for multimodal summarization that can cover both single-modal output summarization and multimodal output summarization. In our framework, we consider three different scenarios and propose the respective unsupervised graph-based multimodal summarization models without the requirement of any manually annotated document-summary pairs for training: (1) generic multimodal ranking, (2) modal-dominated multimodal ranking, and (3) non-redundant text-image multimodal ranking. Furthermore, an image-text similarity estimation model is introduced to measure the semantic similarity between image and text. Experiments show that our proposed models outperform the single-modal summarization methods on both automatic and human evaluation metrics. Besides, our models can also improve the single-modal summarization with the guidance of the multimedia information. This study can be applied as the benchmark for further study on multimodal summarization task.
Developing the Persian Wordnet of Verbs Using Supervised Learning
Authors: Mousavi Zahra , Faili Heshaam
Published: May 2021

Nowadays, wordnets are extensively used as a major resource in natural language processing and information retrieval tasks. Therefore, the accuracy of wordnets has a direct influence on the performance of the involved applications. This paper presents a fully-automated method for extending a previously developed Persian wordnet to cover more comprehensive and accurate verbal entries. At first, by using a bilingual dictionary, some Persian verbs are linked to Princeton WordNet synsets. A feature set related to the semantic behavior of compound verbs as the majority of Persian verbs is proposed. This feature set is employed in a supervised classification system to select the proper links for inclusion in the wordnet. We also benefit from a pre-existing Persian wordnet, FarsNet, and a similarity-based method to produce a training set. This is the largest automatically developed Persian wordnet with more than 27,000 words, 28,000 PWN synsets and 67,000 word-sense pairs that substantially outperforms the previous Persian wordnet with about 16,000 words, 22,000 PWN synsets and 38,000 word-sense pairs.