bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis
Authors: Gerstner Christina , Turcinov Sara , Hensvold Aase H , Chemin Karine , Uchtenhagen Hannes , Ramwadhdoebe Tamara H , Dubnovitsky Anatoly , Kozhukh Genadiy , Rönnblom Lars , Kwok William W , Achour Adnane , Catrina Anca I , Baarsen Lisa G. M. van , Malmström Vivianne 
Published: March 2020

Abstract
Background: HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterization of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described.
Results: Using multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-b, vimentin as well as cartilage intermediate layer protein (CILP).First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors (n=7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (n=14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (n=5) and early RA patients (n=5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (n=10) and found that the group of patients achieving minimum disease activity (DAS28 <2.6) at 6 months follow-up displayed a decrease in the frequency of citrulline-specific T cells.
Conclusions: Our study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterization of antigen-specific T cells in ex vivo patient samples including RA ‘at risk’ subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.
Factors Associated With Low Handgrip Strength in Older People: Data of the Study of Chronic Diseases (EDOC-I)
Authors: Amaral Cledir de Araújo , Amaral Thatiana Lameira Maciel , Monteiro Gina Torres Rego , de Vasconcellos Mauricio Teixeira Leite , Portela Margareth Crisostomo 
Published: March 2020

Abstract
Background Handgrip strength (HGS) is an important health biomarker whose low scores have been shown to be associated with the morbimortality. This study aimed to analyze the factors associated with low HGS in older people in Rio Branco, Acre, Brazil. Methods The study was carried out with data from the Study of Chronic Diseases (EDOC-I) – Older People, a cross-sectional household PAPI probability sample survey performed with 1,016 people aged over 60 residing in Rio Branco in 2014. The low HGS was defined by the 20 th percentile of the maximum HGS by sex and age group. Associations between variables of health status (psychological and physical) and low HGS, by sex, were estimated using logistic regression, expressed by adjusted ORs (aOR). Results Older individuals had lower median HGS than younger individuals (-6.0 kg among men and -2.6 kg among women). Women aged over 80 had, on average, the lower quintile of HGS compared to women of the previous age groups. Factors independently associated with low HGS in men and women, respectively, were low weigh in body mass index [(aOR = 2.80; 95%CI: 1.19, 6.61) and (aOR = 2.61; 95%CI: 1.46, 4.66)], anemia [(aOR= 4.15; 95%CI: 2.09, 8.21) and (aOR = 1.80; 95%CI: 1.06, 3.06)] and diabetes as a risk factor in men (aOR 1.95; 95%CI: 1.00, 3.81). There was a higher chance of low HGS in men with partners (aOR = 2.44; 95%CI: 1.32, 4.51), smokers or former smokers (aOR = 3.25; 95%CI: 1.25, 8.44), with current self-assessment of health worse than the 12 previous months (aOR = 2.21; 95%CI: 1.14, 4.30) and dependence in activities of daily living (aOR = 2.92; 95%CI: 1.35, 6.30). Only among women, there was an increased chance of low HGS associated with altered waist-to-hip ratio (aOR = 1.79; 95%CI: 1.02, 3.12), insomnia (aOR = 1.83; 95%CI: 1.10, 3.03) and physical activity from displacement/occupation (aOR = 1.75; 95%CI: 1.08, 2.84). Conclusion Factors associated with low HGS are not the same between sexes, and the inclusion of HGS as a component of health assessment seems to be a promising strategy for disease prevention and health promotion.
Fear-avoidance beliefs are associated with exercise adherence: Secondary analysis of a randomised controlled trial (RCT) among female healthcare workers with recurrent low back pain
Authors: Taulaniemi Annika , Kankaanpää Markku , Rinne Marjo , Tokola Kari , Parkkari Jari , Suni Jaana Helena 
Published: March 2020

Abstract
Background: Exercise is recommended for the treatment and management of low back pain (LBP) and the prevention of chronicity. Exercise adherence has been only modest in intervention studies among people with musculoskeletal pain. Fear-avoidance beliefs (FABs) are known to affect exercise adherence.The purpose was twofold: to examine which bio-psycho-social factors contributed to exercise adherence during a 6-month neuromuscular exercise intervention among female healthcare workers with recurrent LBP, and to investigate how exercising affects FABs at 6 and 12 months’ follow-up. Methods: Some 219 healthcare workers aged 30–55 years with mild-to-moderate re-current non-specific LBP were originally allocated into: 1) exercise, 2) counselling, 3) combined exercise and counselling, and 4) control groups. In the present secondary analysis, groups 1 and 3 (exercise only and exercise+counselling) were merged to be exercisers and groups 2 and 4 were merged to be non-exercisers. Baseline variables of the exercise compliers (≥24 times over 24 weeks; n=58) were compared to those of the non-compliers (<1 time/week, 0–23 times; n=52). The effects of the exercise programme on FABs were analysed by a generalised linear mixed model according to the intention-to-treat principle (exercisers; n= 110 vs non-exercisers; n=109) at three measurement points (baseline, 6, and 12 months). A per-protocol analysis compared the more exercised to the less exercised and non-exercisers. Results: A low education level (p=0.026), shift work (p=0.023), low aerobic (p=0.048) and musculoskeletal (p=0.043) fitness, and high baseline physical activity-related FABs (p=0.019) were related to low exercise adherence. The exercise programme reduced levels of both physical activity- and work-related FABs, and there was a dose response: FABs reduced more in persons who exercised ≥24 times compared to those who exercised 0-23 times.Conclusion: Healthcare workers who had lower education and fitness levels, worked shifts, and had high physical activity-related FABs had a lower adherence to the 6-month neuromuscular exercise programme. Exercising with good adherence reduced levels of FABs, which have been shown to be linked with prolonged LBP. Motivational strategies should be targeted at persons with low education and fitness levels and high FABs in order to achieve better exercise adherence.
Manuscript Tittle: Women's Experiences of Rectovaginal Fistula: An Ethno- Religious Experience
Authors: Nezhad Fatemeh Touhidi , Jalali Rostam , Karimi Fozieh 
Published: March 2020

Abstract
Background: Obstetric fistulas are one of the most tragic injuries that occur after difficult, prolonged childbirth without timely intervention. These fistulas cause discomfort to patients and result in emotional, social, and even physical suffering. The present study aimed to explore the experiences of women with rectovaginal fistula in Kamyaran city, in Kurdestan province, west of Iran.Methods: In a phenomenological study, 16 patients, healthcare personnel and patients' families were investigated. Purposive sampling was performed and Study participants were interviewed in-depth semi-structured interviews. All interviews were audio-recorded, transcribed verbatim (word by word) and analyzed by Colaizzi's method. To determine the validity of the study, Lincoln and Guba’s criteria, which include credibility, dependability, transferability, and confirmability, was considered.Results: Five general themes and ten sub-themes emerged after investigating interviews. Themes include religious harassment the sub-theme of being defiled), fail (sub-themes of loss and negative attitudes, disrupted sex (the sub-theme of sexual dissatisfaction), consequence (three sub-themes of sleep disturbance, mental crisis, and isolation), and ultimately panic (three sub-themes of humiliation, secrecy, and fear).Conclusion: The rectovaginal fistula is a complex and multifaceted problem with social, individual, familial, religious, and ethnic-environmental dimensions, so there is no simple solution to interact with this problem and there is a need to find a solution, considering the dimensions of the problem and plan for help these patients cope with their disease, and take steps to fully treat it.
The independent indicators for differentiating renal cell carcinoma from renal angiomyolipoma by contrast-enhanced ultrasound
Authors: Author) Hongli Cao(Former Corresponding , Fang Liang , Author) Lin Chen(New Corresponding , Zhan Jia , Diao Xuehong , Liu Yingchun , Lu Chen , Zhang Zhengwang , Chen Yue 
Published: March 2020

Abstract
Background: The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC.
Methods: A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed.
Results: There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML ( P <0.05 for all). Multivariate analysis indicated that perilesional rim-like enhancement ( P =0.035, odds ratio [OR]=9.907, 95% confidence interval [CI]: 1.169-83.971) and fast wash out ( P =0.001, OR =9.755, 95%[CI]: 2.497-38.115) were independent indicators for predicting RCC. The area under the receiver operating characteristic (ROC) curve (AUC) for perilesional rim-like enhancement was 0.838 (95% CI:0.774-0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI:0.768-0.885) with 74.7% sensitivity and 81.8% specificity.
Conclusions: This study indicated that CEUS has value in differentiating RCC and AML. Present perilesional rim-like enhancement and fast wash out may be important indicators for predicting RCC.
Key words: Renal cell carcinoma; angiomyolipoma; contrast-enhanced ultrasound; ultrasonography
The Application and Accuracy of Feature Matching on Automated Cephalometric Superimposition
Authors: Jiang Yiran , Song Guangying , Yu Xiaonan , Dou Yuanbo , Li Qingfeng , Liu Siqi , Han Bing , Xu Tianmin 
Published: March 2020

Abstract
Background: The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and to evaluate the accuracy of this method based on free-hand tracing.
Methods: Twenty-eight pairs of pre-treatment (T1 ) and post-treatment (T2 ) cephalograms were selected. Structural superimpositions of the cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching algorithm. To quantitatively evaluate the differences between the two methods, the hand superimposed patterns were digitized. After automated and hand superimposition of T2 cephalograms to T1 cephalometric templates, landmark distances between paired automated and hand T2 cephalometric landmarks were measured. Differences in hand superimposition among the operators were also calculated.
Results: The T2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between hand and automated superimposition (p > 0.05).
Conclusions: Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research.
Keywords: Digital imaging/radiology, Orthodontic(s), Cephalometric superimposition, Feature Matching, Accuracy
Microglia depletion fails to abrogate inflammation-induced sicknessin mice and rats
Authors: Vichaya Elisabeth G. , Malik Sajida , Sominsky Luba , Ford Bianca G. , Spencer Sarah J. , Dantzer Robert 
Published: March 2020

Abstract
Background: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation.Methods: Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonist of colony stimulating factor-1 receptor, and in rats by a knock-in model in which the diphtheria toxin receptor was expressed under the control of the endogenous fractalkine receptor (Cx3cr1) promoter sequence. After successful microglia depletion, mice and rats were injected with a sickness-inducing dose of lipopolysaccharide according to a 2 (depletion versus control) x 2 (LPS versus saline) factorial design. Sickness was measured by body weight loss and decreased locomotor activity in rats and mice, and reduced voluntary wheel running in mice. Results: Chronic administration of PLX5622 in mice and administration of diphtheria toxin to knock-in rats depleted microglia and peripheral tissue macrophages. However, it did not abrogate the inducible expression of proinflammatory cytokines in the brain in response to LPS and even exacerbated it for some of the cytokines. In accordance with these neuroimmune effects, LPS-induced sickness was not abrogated, rather it was exacerbated when measured by running wheel activity in mice. Conclusions: These findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.
Association of Polybrominated Diphenyl Ether (PBDE) Levels with Biomarkers of Placental Development and Disease during Mid-gestation
Authors: Varshavsky Julia , Robinson Joshua F. , Zhou Yan , Puckett Kenisha A. , Kwan Elaine , Buarpung Sirirak , Aburajab Rayyan , Gaw Stephanie L. , Sen Saunak , Smith Sabrina Crispo , Frankenfield Julie , Park June-Soo , Fisher Susan J. , Woodruff Tracey J. 
Published: March 2020

Abstract
Background

Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function.

Methods

To evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy ( n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion—integrin alpha-1 ( ITGA1) , vascular endothelial-cadherin ( CDH5 ), and metalloproteinase-1 ( MMP1 )–and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues–leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall’s tau correlation and linear regression methods.

Results

PBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE levels and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive).

Conclusions

We found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human granulosa cells by targeting FGD4
Authors: Lin Ji , Huang Huijuan , Lin Liheng , Li Weiwei , Huang Jianfen 
Published: March 2020

Abstract
Background MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in human granulosa cells. Results Downregulation of miR-23a was observed in in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human granulosa cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of ovarian granulosa cells through target FGD4, and may play a role in the pathophysiology of PCOS.
An interpretable machine learning method for detecting novel pathogens
Authors: Zhao Xiaoyong , Wang Ningning 
Published: March 2020

Abstract
Background: According to the World Health Organization (WHO), infectious diseases continue to one of the leading causes of death worldwide. Since the core microbiota flora of humans is largely diverse and horizontal gene transfer (HGT), it is very challenging to determine whether a particular bacterial strain is commensal or pathogenic to humans. With the latest advances in next-generation sequencing (NGS) technology, bioinformatics tools and techniques using NGS data have increasingly been used for the diagnosis and monitoring of infectious diseases. Even if the biological background is not available, the machine learning method can still infer the pathogenic phenotype from the NGS readings, independent of the database of known organisms, and being studied intensively.However, previous methods have not considered opportunistic pathogenic and interpretability of black box model, are not well suited for clinical requirements. Results :In this study, we proposed a novel interpretable machine learning approach (IMLA) to identify the pathogenicity of bacterial genomes: human pathogens (HP), opportunistic pathogenicity (OHP) or non-pathogenicity(NHP), then use the following model-agnostic interpretation methods to interpret model: feature importance, accumulated local effects and Shapley values, due to the model interpretability is essential for healthcare applications. To our knowledge, our paper is the first attempt to infer opportunistic pathogenicity and explain the model. Conclusions: According to the simulation results, our approach IMLA can be a great addition to detect novel pathogens.
The prevalence of type 2 diabetes in people with psychiatric disorders: an umbrella review protocol
Authors: Lindekilde Nanna , Scheuer Stine , Rutters Femke , Henriksen Jan Erik , Rubin Katrine Hass , Lasgaard Mathias , Andersen Gregers Stig , Pouwer Frans 
Published: March 2020

Abstract
Background: Many epidemiological studies have investigated the prevalence of type 2 diabetes in individuals with a psychiatric disorder. In an umbrella review, we aim to systematically summarize existing systematic reviews examining the prevalence of type 2 diabetes in people with a psychiatric disorder. When information is available in the identified systematic reviews, comparisons with control groups without a psychiatric disorder will be made. Furthermore, we aim to assess the quality of the included systematic reviews. Methods: The umbrella review will be based on a comprehensive systematic search of systematic reviews of observational (cross-sectional or longitudinal) studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. Four electronic databases (Embase, PsycINFO, PubMed and the Cochrane Database of Systematic Reviews) will be searched. Retrieved papers will be screened for eligibility by two independent reviewers. Furthermore, the reference lists of all included publications will be screened. Data will be extracted by using an a priori developed data extraction form and two independent reviewers will assess the risk of bias in the included systematic reviews using with the Risk of Bias in Systematic Reviews (ROBIS) tool. A narrative data-synthesis and a subsequent meta-analysis will be made. Discussion: For each psychiatric disorder, the data regarding the prevalence of type 2 diabetes will be summarized and discussed. When possible, comparisons with control groups will be reported and discussed. Finally, future implications and recommendations for clinical care will be presented. Systematic review registration: (registration number) Keywords: Type 2 diabetes, Psychiatric disorder, Prevalence, Umbrella review, Systematic review
An exploratory study of the acceptability of indoor residual spraying for malaria control in upper western Ghana
Authors: Suuron Vitalis Mwinyuri , Mwanri Lillian , Tsourtos George , Owusu-Addo Ebenezer 
Published: March 2020

Abstract
Background: Despite the implementation of the World Health Organisation’s recommended indoor residual spraying (IRS) intervention in the upper west region of Ghana to reduce malaria morbidity and mortality, the uptake of this intervention remains low. This study explores the facilitators and barriers to the acceptability and community uptake of indoor residual spraying in a highly endemic region of Ghana. Methods: The health belief model (HBM) and realist evaluation framework were used to inform the study. A qualitative enquiry was conducted between April to October 2016. Data were collected through focus group discussions and semi-structured interviews with program stakeholders including community members, AngloGold Ashanti malaria control (AGA Mal) spray operators, and AGA Mal officials. Results: A total of 101 people participated in the study. Considerable barriers to community acceptance of indoor residual spraying (IRS) were found, including, dislike of spray insecticides, inadequate information, religious and cultural beliefs, perceived low efficacy of IRS, difficulties with packing, unprofessional conduct of IRS spray operators, and other operational barriers to spraying. Facilitators of IRS uptake included a perceived effectiveness of IRS in preventing malaria and reducing mosquito bites, incidental benefits, respect for authority, training and capacity building, and sensitization activities. Conclusion: The numerous barriers to indoor residual spraying acceptance and implications show that acceptance levels could be improved. However, measures are required to address householders’ concerns and streamline operational barriers to increase community uptake of indoor residual spraying.