bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal immersive trail making-virtual reality paradigm to study cognitive-motor interactions
Authors: Plotnik Meir , Ben-Gal Oran , Doniger Glen M. , Gottlieb Amihai , Bahat Yotam , Cohen Maya , Kimel-Naor Shani , Zeilig Gabi , Beeri Michal Schnaider 
Published: May 2021

Abstract
Background
Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function.

Methods
Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance.

Results
Construct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants.

Conclusions
The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.
Comparison of SARS-CoV-2 indirect and direct RT-qPCR detection methods
Authors: Pearson Joel D. , Trcka Daniel , Lu Suying , Hyduk Sharon J. , Jen Mark , Aynaud Marie-Ming , Hernández J. Javier , Peidis Philippos , Barrios-Rodiles Miriam , Chan Kin , Woodgett Jim , Mazzulli Tony , Attisano Liliana , Pelletier Laurence , Cybulsky Myron I. , Wrana Jeffrey L. , Bremner Rod 
Published: May 2021

AbstractBackgroundSensitive, rapid, and accessible diagnostics continue to be critical to track the COVID-19 pandemic caused by the SARS-CoV-2 virus. RT-qPCR is the gold standard test, and comparison of methodologies and reagents, utilizing patient samples, is important to establish reliable diagnostic pipelines.MethodsHere, we assessed indirect methods that require RNA extraction with direct RT-qPCR on patient samples. Four different RNA extraction kits (Qiagen, Invitrogen, BGI and Norgen Biotek) were compared. For detection, we assessed two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). We also tested and optimized direct, extraction-free detection using these RT-qPCR systems and performed a cost analysis of the different methods evaluated here.ResultsMost RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system provided overall superior performance (lower detection limit, lower Ct values and higher sensitivity), generating comparable results to original clinical diagnostic data, and identifying samples ranging from 65 copies to 2.1 × 105copies of viral genome/μl. However, the BGI detection system is more expensive than other options tested here. With direct RT-qPCR, simply adding an RNase inhibitor greatly improved detection, without the need for any other treatments (e.g. lysis buffers or boiling). The best direct methods detected ~ 10 fold less virus than indirect methods, but this simplified approach reduced sample handling, as well as assay time and cost.ConclusionsWith extracted RNA, the BGI RT-qPCR detection system exhibited superior performance over the Norgen system, matching initial clinical diagnosis with the Seegene Allplex assay. The BGI system was also suitable for direct, extraction-free analysis, providing 78.4% sensitivity. The Norgen system, however, still accurately detected samples with a clinical Ct < 33 from extracted RNA, provided significant cost savings, and was superior to SYBR green assays that exhibited reduced specificity.
Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome
Authors: Liu Wei , Zheng Jian , Ren Xiaohu , Xie Yuxuan , Lin Dafeng , Li Peimao , Lv Yuan , Hoi Maggie Pui Man , Zhang Yanfang , Liu Jianjun 
Published: May 2021

Abstract
Background
Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value.

Methods
Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test.

Results
A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function.

Conclusion
These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.
Determinants of exclusive breastfeeding for the first six months in China: a cross-sectional study
Authors: Shi Huifeng , Yang Yumei , Yin Xiaohan , Li Jia , Fang Jin , Wang Xiaoli 
Published: May 2021

Abstract
Background
Breast milk is the best source of essential nutrients and bioactive components for infants under 6 months. However, little is known about what affects breastfeeding intentions and practices of Chinese mothers. With measures of individual, setting, and sociocultural factors, this study examined determinants of exclusive breastfeeding in the first 6 months of infancy in China.

Methods
Data were obtained from a national cross-sectional survey in China in 2018 that included 5237 infants under 6 months with available measurements of breastfeeding. A 24-h reported food recall method was applied to assess breastfeeding and complementary food intake in the past 24 h. Potential breastfeeding determinants categorized into six aspects were measured: (1) infant health, (2) maternal sociodemographic characteristics, (3) maternal health, (4) breastfeeding support from family, friends, and workplace, (5) social support for breastfeeding, and (6) maternal breastfeeding experiences and knowledge. Reasons for non-commencement or early cessation of breastfeeding were evaluated for non-breastfed infants. For breastfed infants, multivariate logistic regression was used to explore the determinants of exclusive breastfeeding.

Results
About 30 % (29.5%) of infants under 6 months were exclusively breastfed; 2.3% (2.3%) had never been breastfed and 3.2% had ceased breastfeeding. No breast milk (60.7%), maternal illness (13.9%), and infant illness (13.1%) were the top three reasons for non-commencement of breastfeeding. Insufficient breast milk was the reason given for ceasing breastfeeding early by almost two thirds of caregivers who had stopped breastfeeding. The following factors were associated with exclusive breastfeeding: maternal higher education, formal employment with ≥6 months of paid maternity leave, support of the husband and best friends for breastfeeding, a breastfeeding-supportive society, and better breastfeeding knowledge and experiences (a previous successful breastfeeding experience ≥6 months and early initiation of breastfeeding). Maternal age of ≥40 years, caesarean delivery, and infant disease history were associated with non-exclusive breastfeeding.

Conclusions
The exclusive breastfeeding rate is still very low in China. Multidimensional barriers contribute to this situation. A comprehensive intervention framework is needed to increase optimal breastfeeding and achieve substantial public health gains.
HIV testing and its associated factors among street-based female sex workers in Iran: results of a national rapid assessment and response survey
Authors: Ahmadi Sina , Khezri Mehrdad , Roshanfekr Payam , Karimi Salah Eddin , Vameghi Meroe , Ali Delaram , Ahounbar Elahe , Noroozi Mehdi , Shokoohi Mostafa 
Published: May 2021

Abstract
Background
Female sex workers (FSWs) are at a disproportionate risk of sexually transmitted infections and they may face significant barriers to HIV testing. This study aimed to examine HIV testing prevalence and its associated factors among street-based FSWs in Iran.

Method
A total of 898 FSWs were recruited from 414 venues across 19 major cities in Iran between October 2016 and March 2017. Eligible FSWs were women aged 18 years of age who had at least one commercial sexual intercourse in the previous year. HIV testing was defined as having tested for HIV in the lifetime. Bivariable and multivariable logistic regression were used to examine the correlates of HIV testing. We report adjusted odds ratios (aOR) and their 95% confidence intervals (CI).

Result
Overall, 57.8% (95%CI: 20.0, 88.0) of participants reported having tested for HIV, and HIV prevalence among FSWs who tested for HIV was 10.3% (95%CI: 7.5, 13.0). The multivariable model showed that unstable housing (aOR: 8.86, 95%CI: 2.68, 29.32) and drug use (aOR: 3.47, 95%CI: 1.33, 9.06) were associated with increased likelihood of HIV testing. However, FSWs with a higher level of income were less likely to be tested for HIV (aOR: 0.09, 95%CI: 0.02, 0.43).

Conclusion
Almost one in ten street-based FSWs had never tested for HIV. These findings suggest the need for evidence-based strategies such as outreach support and HIV self-testing to improve HIV testing in this marginalized population.
Ostial lesion of the anterior descending coronary artery treated via Szabo technique supported by stent boost imaging: a case report
Authors: Wang Guangliang , Wu Xuemei 
Published: May 2021

Abstract
Background
Stenosis at the opening and bifurcation of the anterior descending branch and circumflex branch around the end of the left main trunk is difficult to repair. Accurate positioning of a stent is the key problem.

Case presentations
Here we report the case of a 61-year-old man who suffered from paroxysmal chest pain for 1 year, without history of diabetes or hypertension. The coronary computed tomography showed mixed plaques in the proximal part of the anterior descending artery, with stenosis severe at 80–90%. The emergency coronary angiography showed occlusion of the anterior descending artery. During percutaneous coronary intervention, a drug-eluting stent was implanted into the anterior descending artery using the Szabo technique, supported by stent boost (StentBoost) imaging to pinpoint the location of the lesion. The patient’s paroxysmal chest pain was relieved after the procedure.

Conclusion
We used StentBoost to verify the accuracy of stent placement and the Szabo technique to rectify long-term coronary stenosis, which achieved satisfactory results. Combining the Szabo technique with StentBoost imaging was helpful to accurately evaluate the area and locate the stent when treating this ostial lesion of the anterior descending coronary artery.
Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss
Authors: Miwa Toru , Wei Fan-yan , Tomizawa Kazuhito 
Published: May 2021

AbstractMitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6 mouse model. Compared to control C57BL/6 mice, Cdk5rap1-knockout female mice displayed hearing loss phenotypically similar to AHL from an early age. The premature hearing loss in Cdk5rap1-knockout mice was associated with the degeneration of the spiral ligament and reduction of endocochlear potentials following the loss of auditory sensory cells. Furthermore, cultured primary mouse embryonic fibroblasts displayed early onset of cellular senescence associated with high oxidative stress and cell death. These results indicate that the CDK5RAP1 deficiency-induced defective mitochondrial translation might cause early hearing loss through the induction of cellular senescence and cochlear dysfunction in the inner ear. Our results suggest that the accumulation of dysfunctional mitochondria might promote AHL progression. Furthermore, our findings suggest that mitochondrial dysfunction and dysregulated mitochondrial tRNA modifications mechanistically cause AHL. Understanding the mechanisms underlying AHL will guide future clinical investigations and interventions in the attempt to mitigate the consequences of AHL.
The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China
Authors: Ni Jing , Cheng Xianzhong , Zhao Qian , Dai Zhiqin , Xu Xia , Guo Wenwen , Gu Hongyuan , Zhou Rui , Wang Yan , Chen Xiaoxiang 
Published: May 2021

Abstract
Background
Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China.

Methods
Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity.

Results
Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060–0.759) and disease control rate (DCR) of 50% (95%CI = 0.140–0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3–4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event.

Conclusion
It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.
Low prevalence of active trachoma and associated factors among children aged 1–9 years in rural communities of Metema District, Northwest Ethiopia: a community based cross-sectional study
Authors: Ayelgn Kessete , Guadu Tadesse , Getachew Atalay 
Published: May 2021

Abstract
Background
Trachoma is an infectious disease of the eye caused by Chlamydia trachomatis and transmitted via contact with eye discharge from infected persons and leading to blindness worldwide. Children less than 9 years of age affected more seriously. The disease is common where access to water and sanitation are limited.

Objective
To determine the prevalence of active trachoma and associated factors among children aged 1–9 years in rural communities of Metema District, West Gondar Zone, Northwest Ethiopia.

Method
A community based cross-sectional study design was used to collect data from 792 children aged 1–9 years old in Metema district from April to May 2018. Multistage sampling technique was used to select the study participants. Pretested interviewer-administered structured questionnaire and eye examination using binocular loupe to differentiate trachoma cases was the data collection methods and tools. The bivariable and multivariable binary logistic regression model was employed for analysis. P-value < 0.05 was considered to declare statistical significance.

Results
A total of 752 children aged l-9 years were enrolled in this study with response rate of 94.9%. The overall prevalence of active trachoma among the study participants was 11.8% (95% CI, 9.5–13.9). Unprotected source of water (AOR = 4.7; 95% CI: 2.5–8.9), lower household water consumption (AOR = 2.8; 95% CI: 1.3–6.0), improper latrine utilization (AOR = 3.2; 95% CI: 1.5–6.7), and frequency of face washing once per day (AOR = 5.3; 95% CI: 1.2–26.6) were the factors significantly associated with active trachoma.

Conclusion
The current study revealed a lower overall prevalence of active trachoma (11.8%) than the WHO threshold prevalence (20%) used to declare it as a severe public health problem. All residents and health professional should collaborate on trachoma prevention by implementing the WHO SAFE strategy- surgery for trichiasis, antibiotics, facial cleanliness and environmental improvement for further trachoma elimination.
treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses
Authors: Huang Ruizhu , Soneson Charlotte , Germain Pierre-Luc , Schmidt Thomas S.B. , Mering Christian Von , Robinson Mark D. 
Published: May 2021

AbstracttreeclimbRis for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or leaves that contain features of interest, in a data-driven way. It outperforms currently available methods on synthetic data, and we highlight the approach on various applications, including microbiome and microRNA surveys as well as single-cell cytometry and RNA-seq datasets. With the emergence of various multi-resolution genomic datasets,treeclimbRprovides a thorough inspection on entities across resolutions and gives additional flexibility to uncover biological associations.
A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks
Authors: Yuan Chongze , Chen Haojie , Tu Shiqi , Huang Hsin-Yi , Pan Yunjian , Gui Xiuqi , Kuang Muyu , Shen Xuxia , Zheng Qiang , Zhang Yang , Cheng Chao , Hong Hui , Tao Xiaoting , Peng Yizhou , Yao Xingxin , Meng Feilong , Ji Hongbin , Shao Zhen , Sun Yihua 
Published: May 2021

AbstractBackgroundLung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression.ResultsA high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD.ConclusionsOur study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.