bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial
Authors: Reddy Amit K. , Miller D. Claire , Sura Amol A. , Rathinam SR , Gonzales John A , Thundikandy Radhika , Kanakath Anuradha , Murugan Bala , Vedhanayaki Rajesh , Lim Lyndell L. , Suhler Eric B. , Doan Thuy , Al-Dhibi Hassan A. , Goldstein Debra A. , Arellanes-Garcia Lourdes , Acharya Nisha R 
Published: June 2023

Abstract
Background
The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis.

Main body
This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF.

Conclusion
Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.
Deep learning-based classification model for GPR151 activator activity prediction
Authors: Xu Huangchao , Zhang Baohua , Liu Qian 
Published: June 2023

AbstractBackgroundGPR151 is a kind of protein belonging to G protein-coupled receptor family that is closely associated with a variety of physiological and pathological processes.The potential use of GPR151 as a therapeutic target for the management of metabolic disorders has been demonstrated in several studies, highlighting the demand to explore its activators further. Activity prediction serves as a vital preliminary step in drug discovery, which is both costly and time-consuming. Thus, the development of reliable activity classification model has become an essential way in the process of drug discovery, aiming to enhance the efficiency of virtual screening.ResultsWe propose a learning-based method based on feature extractor and deep neural network to predict the activity of GPR151 activators. We first introduce a new molecular feature extraction algorithm which utilizes the idea of bag-of-words model in natural language to densify the sparse fingerprint vector. Mol2vec method is also used to extract diverse features. Then, we construct three classical feature selection algorithms and three types of deep learning model to enhance the representational capacity of molecules and predict activity label by five different classifiers. We conduct experiments using our own dataset of GPR151 activators. The results demonstrate high classification accuracy and stability, with the optimal model Mol2vec-CNN significantly improving performance across multiple classifiers. The svm classifier achieves the best accuracy of 0.92 and F1 score of 0.76 which indicates promising applications for our method in the field of activity prediction.ConclusionThe results suggest that the experimental design of this study is appropriate and well-conceived. The deep learning-based feature extraction algorithm established in this study outperforms traditional feature selection algorithm for activity prediction. The model developed can be effectively utilized in the pre-screening stage of drug virtual screening.
Probing stress-regulated ordering of the plant cortical microtubule array via a computational approach
Authors: Li Jing , Szymanski Daniel B. , Kim Taeyoon 
Published: June 2023

Abstract
Background
Morphological properties of tissues and organs rely on cell growth. The growth of plant cells is determined by properties of a tough outer cell wall that deforms anisotropically in response to high turgor pressure. Cortical microtubules bias the mechanical anisotropy of a cell wall by affecting the trajectories of cellulose synthases in the wall that polymerize cellulose microfibrils. The microtubule cytoskeleton is often oriented in one direction at cellular length-scales to regulate growth direction, but the means by which cellular-scale microtubule patterns emerge has not been well understood. Correlations between the microtubule orientation and tensile forces in the cell wall have often been observed. However, the plausibility of stress as a determining factor for microtubule patterning has not been directly evaluated to date.

Results
Here, we simulated how different attributes of tensile forces in the cell wall can orient and pattern the microtubule array in the cortex. We implemented a discrete model with transient microtubule behaviors influenced by local mechanical stress in order to probe the mechanisms of stress-dependent patterning. Specifically, we varied the sensitivity of four types of dynamic behaviors observed on the plus end of microtubules – growth, shrinkage, catastrophe, and rescue – to local stress. Then, we evaluated the extent and rate of microtubule alignments in a two-dimensional computational domain that reflects the structural organization of the cortical array in plant cells.

Conclusion
Our modeling approaches reproduced microtubule patterns observed in simple cell types and demonstrated that a spatial variation in the magnitude and anisotropy of stress can mediate mechanical feedback between the wall and of the cortical microtubule array.
Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges
Authors: Sato Daisuke , Takami Hirokazu , Takayanagi Shunsaku , Taoka Kazuki , Tanaka Mariko , Matsuura Reiko , Tanaka Shota , Saito Nobuhito 
Published: June 2023

Abstract
Background
Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described.

Case presentation
A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and “other iatrogenic immunodeficiency-associated lymphoproliferative disorder” (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD.

Conclusions
This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.
The role of gender inequities in women's access to reproductive health services: a population-level study of Simiyu Region Tanzania
Authors: Tesha Jane , Fabian Agatha , Mkuwa Serafina , Misungwi Gaspery , Ngalesoni Frida 
Published: June 2023

Abstract
Background
Amref Health Africa, with support from Global Affairs Canada, examines if women's access to reproductive health services in Tanzania is affected by Gender social norms, decision-making power, roles and responsibility, and access to resources in relation to the utilization of reproductive Health Services in Tanzania. A Gender Need Assessment (GNA) was conducted in five districts in ' 'Tanzania Simiyu Region to improve the infrastructure, supply, quality, and demand for integrated Reproductive, Maternal, Newborn, and Child and Adolescent Health (RMNCAH), Nutrition, and Water, Sanitation, and Hygiene (WASH) services. The analysis identifies gender as a fundamental maternal and child health driver through existing gender inequality at the household and community levels that dictates women's status.

Methods
The qualitative assessment involved data collected from gender- and age-desegregated focus group discussions (FGDs) and in-depth interviews (IDIs) of key informants in three districts; Bariadi, Busega, and Meatu, in Simiyu region, Tanzania. Participants comprised 8-10 married women and men, unmarried women and men, and adolescent boys and girls. A total of 129 participants were involved in the FGDs.

Results
This paper reports the critical drivers influencing gender inequality in Simiyu by detailing how Gender inequality affected women's access to reproductive health care in relation to; gender social norms, decision-making power, access to resources at the household and community level, roles and responsibilities, including men's and 'boys' roles are more valued than the roles and responsibilities of women and girls resulted to limited free time to do things for themselves, such as visiting the health facilities for RMNCAH.

Conclusions
This paper explored gender-based enablers and/or barriers influencing women and girls' realization of their sexual and reproductive health and rights. It was found that social norms, decision-making powers, and lack of access to and control over resources presented as key barriers. In contrast, continuous community sensitization and increased scope of women's participation in decision-making served as enabling environment to overcome gender inequities that influence woman's use of RMNCAH services in Tanzania. Such insights will shape interventions geared towards valuing differences in a manner that overcome gender inequities that influence woman's use of RMNCAH services in Tanzania.
The predictors of unsuppressed viremia among PLHIV: a cross-sectional study in Ghana
Authors: Owusu Lydia Boampong , Ababio Christiana , Boahene Selina , Zakaria Abdul-Fatawu Suglo , Emikpe Abigael Omowumi , Dwumfour Catherine Kroamah , Appiagyei Kofi Antwi , Apiribu Felix 
Published: June 2023

Abstract
Background
Unsuppressed viremia in HIV infected patients is generally associated with increased rates of disease transmission and poor patient survival. This study assessed the socio-demographic determinants of People Living with HIV/AIDS, having viral load non-suppression and who are receiving antiretroviral therapy in a District Hospital in Ghana.

Methods
The study utilized the cross-sectional research design with both primary and secondary data conducted from September to October 2021 in Ghana. Data were collected from 331 PLHIV who were placed on Anti-Retroviral Therapy (ART) for more than 12 months at the ART centre at a District Hospital in Ghana. Unsuppressed viremia was defined as plasma viral load of ≥ 1000 copies/mL after 12 months on an ART with effective adherent support. A structured questionnaire was used to collect primary data on participants and a Secondary data was also collected from patients’ folders, hospital registers and the computerized health information systems at the study site. SPSS was used to analyse descriptive and inferential data. Pearson’s chi-square and Fisher’s exact test were used to assess the independent determinants of viral load non-suppression. Pearson’s chi-square test was used for tests giving ≤ 20% of expected cell counts less than five while Fisher’s exact test was used for tests giving > 20% of expected cell counts less than five. A p value of < 0.05 was considered statistically significant.

Results
Out of the 331 PLHIV who participated in the study, 174 (53%) were female and 157 (47%) were Male. The study found viral load non-suppression of 19% with age (p = 0.03), income (p = 0.02), employment (p = 0.04), means of transportation (p = 0.02), cost of transportation to the ART centre (p = 0.03) and level of medication adherence (p = 0.02) as determinants of viral load non-suppression.

Conclusion
There was a low level of viral load non-suppression among PLHIV after 12 months of active antiretroviral therapy with age, income, employment, means of transportation, cost of transportation and level of medication adherence influencing viral non-suppression. Thus, ART drugs and services should be decentralized to the community health workers’ level within the various localities of patients to decrease the economic consequences involved in accessing health care for PLHIV/AIDS. This will minimize defaulting, improve adherence and promote viral load suppression.
Single-use flexible bronchoscopes vs traditional reusable flexible bronchoscopes: a prospective controlled study
Authors: He Shuzhen , Xie Lihua , Liu Jianming , Zou Lijun 
Published: June 2023

Abstract
Background
Single-use flexible bronchoscopes(SFB) eliminate the risk of bronchoscopy-related infection compared with traditional reusable flexible bronchoscopes(RFB). At present, there is no comparative study between SFB and RFB in the aspects of biopsy and interventional therapy. This study aims to explore whether SFB can perform complex bronchoscopic procedures such as transbronchial biopsies just like RFB.

Methods
We conducted a prospective controlled study. A total of 45 patients who required bronchoscopic biopsy in our hospital from June 2022 to December 2022 were enrolled. The patients were divided into the SFB group and the RFB group, and routine bronchoscopy, bronchoalveolar lavage, and biopsy were performed respectively. Data on the time of routine bronchoscopy, the recovery rate of bronchoalveolar lavage fluid(BALF), biopsy time, and bleeding volume were collected. Then we used the two-sample t-test and the χ2 test to assess the performance differences between SFB and RFB. We also designed a questionnaire to compare the performance between SFB and RFB by different bronchoscope operators.

Results
The routine examination time of SFB and RFB was 3.40 ± 0.50 min and 3.55 ± 0.42 min, respectively. There was no significant difference between the two groups (P = 0.308). The recovery rate of BALF was (46.56 ± 8.22) % in the SFB group and (47.00 ± 8.07) in the RFB group, without a significant difference between the two groups(P = 0.863). The biopsy time was similar(4.67 ± 0.51 min VS 4.57 ± 0.45 min) in both groups, with no significant difference(P = 0.512). The positive biopsy rate was 100% in both groups, with no significant difference. Overall, the bronchoscope operators were generally satisfied with SFB.

Conclusion
SFBs are non-inferior to RFBs in routine bronchoscopy, bronchoalveolar lavage, and biopsy. It is suggested that SFBs have a wider clinical application.
Development and validation of a machine learning model to predict imminent new vertebral fractures after vertebral augmentation
Authors: Jiang Yang , Cai Jinhui , Zeng Yurong , Ye Haoyi , Yang Tingqian , Liu Zhifeng , Liu Qingyu 
Published: June 2023

Abstract
Background
Accurately predicting the occurrence of imminent new vertebral fractures (NVFs) in patients with osteoporotic vertebral compression fractures (OVCFs) undergoing vertebral augmentation (VA) is challenging with yet no effective approach. This study aim to examine a machine learning model based on radiomics signature and clinical factors in predicting imminent new vertebral fractures after vertebral augmentation.

Methods
A total of 235 eligible patients with OVCFs who underwent VA procedures were recruited from two independent institutions and categorized into three groups, including training set (n = 138), internal validation set (n = 59), and external validation set (n = 38). In the training set, radiomics features were computationally retrieved from L1 or adjacent vertebral body (T12 or L2) on T1-w MRI images, and a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm (LASSO). Predictive radiomics signature and clinical factors were fitted into two final prediction models using the random survival forest (RSF) algorithm or COX proportional hazard (CPH) analysis. Independent internal and external validation sets were used to validate the prediction models.

Results
The two prediction models were integrated with radiomics signature and intravertebral cleft (IVC). The RSF model with C-indices of 0.763, 0.773, and 0.731 and time-dependent AUC (2 years) of 0.855, 0.907, and 0.839 (p < 0.001 for all) was found to be better predictive than the CPH model in training, internal and external validation sets. The RSF model provided better calibration, larger net benefits (determined by decision curve analysis), and lower prediction error (time-dependent brier score of 0.156, 0.151, and 0.146, respectively) than the CPH model.

Conclusions
The integrated RSF model showed the potential to predict imminent NVFs following vertebral augmentation, which will aid in postoperative follow-up and treatment.
Investigating discrimination in the workplace. Translation and validation of the Everyday Discrimination Scale for nursing staff in Germany
Authors: Ulusoy Nazan , Nienhaus Albert , Brzoska Patrick 
Published: June 2023

Abstract
Background
The Everyday Discrimination Scale (EDS) is a frequently used questionnaire in the field of health and social psychology that aims to explore perceptions of discrimination, especially instances of injustice related to various diversity characteristics. No adaptation to health care staff exists. The present study translates and adapts the EDS to nursing staff in Germany and examines its reliability and factorial validity as well as its measurement equivalence between men and women and different age groups.

Methods
The study was based on an online survey conducted among health care staff of two hospitals and two inpatient care facilities in Germany. The EDS was translated using a forward-backward translation approach. Direct maximum likelihood confirmatory factor analysis (CFA) was conducted to examine the factorial validity of the adapted EDS. Differential item functioning (DIF) related to age and sex was investigated by means of multiple indicators, multiple causes (MIMIC) models.

Results
Data on 302 individuals was available, of whom 237 (78.5%) were women. The most commonly employed one-factor, 8-item baseline model of the adapted EDS showed a poor fit (RMSEA = 0.149; CFI = 0.812; TLI = 0.737; SRMR = 0.072). The model fit improved considerably after including three error covariances between items 1 and 2, items 4 and 5, and items 7 and 8 (RMSEA = 0.066; CFI = 0.969; TLI = 0.949; SRMR = 0.036). Item 4 showed DIF related to sex and age, item 6 showed DIF related to age. DIF was moderate in size and did not bias the comparison between men and women or between younger and older employees.

Conclusions
The EDS can be considered a valid instrument for the assessment of discrimination experiences among nursing staff. Given that the questionnaire, similar to other EDS adaptations, may be prone to DIF and also considering that some error covariances need to be parameterized, latent variable modelling should be used for the analysis of the questionnaire.
Regulation of dental consultations in primary health care and performance of services in dental speciality centers
Authors: da Silva Bárbara Campos , Buzinaro Giovana Soares , Cabral Jhenyffer Andrade Viana , da Cunha Inara Pereira , de Lacerda Valéria Rodrigues , Bomfim Rafael Aiello 
Published: June 2023

Abstract
Objective
This study analyzed the regulation of dental specialty centers (CEOs) coordinated exclusively by Primary Health Care (PHC) in four primary outcomes: access and dental consultation, reception services, bonding and responsibility, and social participation.

Methods
A cross-sectional study was carried out using secondary data from the National Program for the Improvement of Access and Quality of Dental Specialty Centers (PMAQ-CEO): second cycle, using multilevel logistic regression to calculate the odds ratio (OR) and individual covariates.

Results
The analytical sample consisted of 9,599 CEO users who had completed all the variables analyzed. Of these, 63.5% were referred to the CEO by PHC. Dental care regulated by PHC was related to better access (OR 1.36, CI 95% 1.10–1.68), better reception (OR 1.33, CI 95% 1.03–1.71), better bonding and responsibility (OR 1.36, CI 95% 0.91–2.04), and social participation (OR 1.13, CI 95% 0.93–1.35) compared to those not regulated by primary health care as the exclusive pathway.

Conclusion
The regulation of access to the CEO coordinated by PHC presented the best performance. It is suggested that this form of PHC regulation, as a route for dental specialty centers, can be established in the national oral health care policy for better service performance.
Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing
Authors: Singh Ashish Kumar , Talseth-Palmer Bente , Xavier Alexandre , Scott Rodney J. , Drabløs Finn , Sjursen Wenche 
Published: June 2023

AbstractBackgroundHereditary genetic mutations causing predisposition to colorectal cancer are accountable for approximately 30% of all colorectal cancer cases. However, only a small fraction of these are high penetrant mutations occurring in DNA mismatch repair genes, causing one of several types of familial colorectal cancer (CRC) syndromes. Most of the mutations are low-penetrant variants, contributing to an increased risk of familial colorectal cancer, and they are often found in additional genes and pathways not previously associated with CRC. The aim of this study was to identify such variants, both high-penetrant and low-penetrant ones.MethodsWe performed whole exome sequencing on constitutional DNA extracted from blood of 48 patients suspected of familial colorectal cancer and used multiple in silico prediction tools and available literature-based evidence to detect and investigate genetic variants.ResultsWe identified several causative and some potentially causative germline variants in genes known for their association with colorectal cancer. In addition, we identified several variants in genes not typically included in relevant gene panels for colorectal cancer, includingCFTR,PABPC1andTYRO3, which may be associated with an increased risk for cancer.ConclusionsIdentification of variants in additional genes that potentially can be associated with familial colorectal cancer indicates a larger genetic spectrum of this disease, not limited only to mismatch repair genes. Usage of multiple in silico tools based on different methods and combined through a consensus approach increases the sensitivity of predictions and narrows down a large list of variants to the ones that are most likely to be significant.