bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of pediatric rheumatology telehealth satisfaction during the COVID-19 pandemic
Authors: Waqar-Cowles Lindsay N. , Chuo John , Weiss Pamela F. , Gmuca Sabrina , LaNoue Marianna , Burnham Jon M. 
Published: December 2021

Abstract
Background
During the Coronavirus disease 2019 pandemic, ambulatory pediatric rheumatology healthcare rapidly transformed to a mainly telehealth model. However, pediatric patient and caregiver satisfaction with broadly deployed telehealth programs remains largely unknown. This study aimed to evaluate patient/caregiver satisfaction with telehealth and identify the factors associated with satisfaction in a generalizable sample of pediatric rheumatology patients.

Methods
Patients with an initial telehealth video visit with a rheumatology provider between April and June 2020 were eligible. All patients/caregivers were sent a post-visit survey to assess a modified version of the Telehealth Usability Questionnaire (TUQ) and demographic and clinical characteristics. TUQ total and sub-scale (usefulness, ease of use, effectiveness, satisfaction) scores were calculated and classified as “positive” based on responses of “agree” or “strongly agree” on a 5-point Likert scale. Results were analyzed using standard descriptive statistics and Wilcoxon signed rank testing. The association between demographic and clinical characteristics with TUQ scores was assessed using univariate linear regression.

Results
597 patients/caregivers met inclusion criteria, and the survey response rate was 42% (n = 248). Juvenile idiopathic arthritis was the most common diagnosis (33.5%). The majority of patients were diagnosed greater than 6 months previously (72.6%) and were prescribed chronic medications (59.7%). The median total TUQ score was 4 (IQR: 4–5) with positive responses in 81% of items. Of the subscales, usefulness scores were lowest (median: 4, p < 0.001). Telehealth saves time traveling was the highest median item score (median = 5, IQR: 4–5). Within subscales, items that scored significantly lower included convenience, providing for needs, seeing rheumatologist as well as in person, and being an acceptable way to receive rheumatology services (all p < 0.001). There were no significant demographic or clinical features associated with TUQ scores.

Conclusions
Our results suggest telehealth is a promising mode of healthcare delivery for pediatric rheumatic diseases but also identifies opportunities for improvement. Innovation and research are needed to design a telehealth system that delivers high quality and safe care that improves healthcare outcomes. Since telehealth is a rapidly emerging form of pediatric rheumatology care, improved engagement and training of patients, caregivers, and providers may help improve the patient experience in the future.
Bispecific antibody-activated T cells enhance NK cell-mediated antibody-dependent cellular cytotoxicity
Authors: Wang Zhaoming , Yin Chaobo , Lum Lawrence G. , Simons Andrean , Weiner George J. 
Published: December 2021

AbstractResistance to anti-cancer monoclonal antibody (mAb) therapy remains a clinical challenge. Previous work in our laboratory has shown that T cell help in the form of interleukin-2 maintains long-term NK cell viability and NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Lack of such T cell help may be a potential mechanism for resistance to mAb therapy. Here, we evaluate whether concomitant treatment with anti-CD3 × anti-cancer bispecific antibodies (bsAbs) can overcome this resistance by enhancing T cell help, and thereby maintaining long-term NK cell-mediated ADCC. Normal donor peripheral blood mononuclear cells were depleted of T cells, replenished with defined numbers of autologous T cells (from 0.75 to 50%) and co-cultured with mono-/bispecific antibody-treated target tumor cells for up to 7 days. At low T cell concentrations, bsAb-activated T cells (mainly CD4+ T cells) were more effective than resting T cells at maintaining NK cell viability and ADCC. Brief (4 h to 2 day) bsAb exposure was sufficient to enhance long-term ADCC by NK cells. These findings raise the hypothesis that local T cell activation mediated by systemic treatment with anti-CD3 X anti-cancer bsAb may enhance the anti-tumor efficacy of monospecific mAbs that mediate their primary therapeutic effect via NK-mediated ADCC.
Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes
Authors: Rezaei-Lotfi Saba , Vujovic Filip , Simonian Mary , Hunter Neil , Farahani Ramin M. 
Published: December 2021

AbstractBackgroundTransdifferentiation describes transformation in vivo of specialized cells from one lineage into another. While there is extensive literature on forced induction of lineage reprogramming in vitro, endogenous mechanisms that govern transdifferentiation remain largely unknown. The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming.ResultsWe show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.ConclusionsThese findings suggest that the global transcriptional landscape not only shapes the functional cellular identity of pericytes, but also stabilizes lineage memory by silencing the competing neural program within a repressed chromatin state.
Development of a core outcome set (COS) for studies relating to awareness and clinical management of reduced fetal movement: study protocol
Authors: Hayes Dexter J. L. , Devane Declan , Dumville Jo C. , Smith Valerie , Walsh Tanya , Heazell Alexander E. P. 
Published: December 2021

AbstractBackgroundConcerns regarding reduced fetal movements (RFM) are reported in 5–15% of pregnancies, and RFM are associated with adverse pregnancy outcomes including fetal growth restriction and stillbirth. Studies have aimed to improve pregnancy outcomes by evaluating interventions to raise awareness of RFM in pregnancy, such as kick counting, evaluating interventions for the clinical management of RFM, or both. However, there is not currently a core outcome set (COS) for studies of RFM. This study aims to create a COS for use in research studies that aim to raise awareness of RFM and/or evaluate interventions for the clinical management of RFM.MethodsA systematic review will be conducted, to identify outcomes used in randomised and non-randomised studies with control groups that aimed to raise awareness of RFM (for example by using mindfulness techniques, fetal movement counting, or other tools such as leaflets or mobile phone applications) and/or that evaluated the clinical management of RFM.An international Delphi consensus will then be used whereby stakeholders will rate the importance of the outcomes identified in the systematic review in (i) awareness and (ii) clinical management studies. The preliminary lists of outcomes will be discussed at a consensus meeting where one final COS for awareness and management, or two discrete COS (one for awareness and one for management), will be agreed upon.DiscussionA well-developed COS will provide researchers with the minimum set of outcomes that should be measured and reported in studies that aim to quantify the effects of interventions.
Teaching reproducible research for medical students and postgraduate pharmaceutical scientists
Authors: Meid Andreas D. 
Published: December 2021

AbstractIn medicine and other academic settings, (doctoral) students often work in interdisciplinary teams together with researchers of pharmaceutical sciences, natural sciences in general, or biostatistics. They should be fundamentally taught good research practices, especially in terms of statistical analysis. This includes reproducibility as a central aspect. Acknowledging that even experienced researchers and supervisors might be unfamiliar with necessary aspects of a perfectly reproducible workflow, a lecture series on reproducible research (RR) was developed for young scientists in clinical pharmacology. The pilot series highlighted definitions of RR, reasons for RR, potential merits of RR, and ways to work accordingly. In trying to actually reproduce a published analysis, several practical obstacles arose. In this article, reproduction of a working example is commented to emphasize the manifold facets of RR, to provide possible explanations for difficulties and solutions, and to argue that harmonized curricula for (quantitative) clinical researchers should include RR principles. These experiences should raise awareness among educators and students, supervisors and young scientists. RR working habits are not only beneficial for ourselves or our students, but also for other researchers within an institution, for scientific partners, for the scientific community, and eventually for the public profiting from research findings.
The ENmix DNA methylation analysis pipeline for Illumina BeadChip and comparisons with seven other preprocessing pipelines
Authors: Xu Zongli , Niu Liang , Taylor Jack A. 
Published: December 2021

AbstractBackgroundIllumina DNA methylation arrays are high-throughput platforms for cost-effective genome-wide profiling of individual CpGs. Experimental and technical factors introduce appreciable measurement variation, some of which can be mitigated by careful “preprocessing” of raw data.MethodsHere we describe the ENmix preprocessing pipeline and compare it to a set of seven published alternative pipelines (ChAMP, Illumina, SWAN, Funnorm, Noob, wateRmelon, and RnBeads). We use two large sets of duplicate sample measurements with 450 K and EPIC arrays, along with mixtures of isogenic methylated and unmethylated cell line DNA to compare raw data and that preprocessed via different pipelines.ResultsOur evaluations show that the ENmix pipeline performs the best with significantly higher correlation and lower absolute difference between duplicate pairs, higher intraclass correlation coefficients (ICC) and smaller deviations from expected methylation level in mixture experiments. In addition to the pipeline function, ENmix software provides an integrated set of functions for reading in raw data files from mouse and human arrays, quality control, data preprocessing, visualization, detection of differentially methylated regions (DMRs), estimation of cell type proportions, and calculation of methylation age clocks. ENmix is computationally efficient, flexible and allows parallel computing. To facilitate further evaluations, we make all datasets and evaluation code publicly available.ConclusionCareful selection of robust data preprocessing methods is critical for DNA methylation array studies. ENmix outperformed other pipelines in our evaluations to minimize experimental variation and to improve data quality and study power.
A likelihood ratio test for the homogeneity of between-study variance in network meta-analysis
Authors: Hu Dapeng , Wang Chong , O’Connor Annette M. 
Published: December 2021

Abstract
Background
Network meta-analysis (NMA) is a statistical method used to combine results from several clinical trials and simultaneously compare multiple treatments using direct and indirect evidence. Statistical heterogeneity is a characteristic describing the variability in the intervention effects being evaluated in the different studies in network meta-analysis. One approach to dealing with statistical heterogeneity is to perform a random effects network meta-analysis that incorporates a between-study variance into the statistical model. A common assumption in the random effects model for network meta-analysis is the homogeneity of between-study variance across all interventions. However, there are applications of NMA where the single between-study assumption is potentially incorrect and instead the model should incorporate more than one between-study variances.

Methods
In this paper, we develop an approach to testing the homogeneity of between-study variance assumption based on a likelihood ratio test. A simulation study was conducted to assess the type I error and power of the proposed test. This method is then applied to a network meta-analysis of antibiotic treatments for Bovine respiratory disease (BRD).

Results
The type I error rate was well controlled in the Monte Carlo simulation. We found statistical evidence (p value = 0.052) against the homogeneous between-study variance assumption in the network meta-analysis BRD. The point estimate and confidence interval of relative effect sizes are strongly influenced by this assumption.

Conclusions
Since homogeneous between-study variance assumption is a strong assumption, it is crucial to test the validity of this assumption before conducting a network meta-analysis. Here we propose and validate a method for testing this single between-study variance assumption which is widely used for many NMA.
Effect of commuting on the risk of COVID-19 and COVID-19-induced anxiety in Japan, December 2020
Authors: Ando Hajime , Ikegami Kazunori , Nagata Tomohisa , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa , Ogami Akira ,   for the CORoNaWork Project
Published: December 2021

Abstract
Background
To prevent the spread of coronavirus disease (COVID-19), it is important to avoid 3Cs (closed spaces, crowded places, and close-contact settings). However, the risk of contact with an unspecified number of people is inevitable while commuting to and from work. In this study, we investigated the relationship between commuting, and the risk of COVID-19 and COVID-19-induced anxiety.

Methods
An internet-based questionnaire survey was conducted to obtain a dataset from 27,036 respondents. One-way commuting time was evaluated using a five-case method. The commuting distance was estimated using zip codes of the home and workplace. Logistic regression analysis was performed with the following outcomes: COVID-19 risk, close contact, infection anxiety, and infection anxiety due to commuting. Commuting distance and commuting time were analyzed separately in the model. We excluded participants with incalculable commuting distance, commuting distance exceeding 300 km, commuting distance of 0 km, or who telecommuted at least once a week.

Results
The total number of participants included in the analysis was 14,038. The adjusted odds ratios (aORs) of using public transportation for severe acute respiratory syndrome coronavirus 2 infection were 4.17 (95% confidence interval [CI]: 2.51–6.93) (commuting time) and 5.18 (95% CI: 3.06–8.78) (commuting distance). The aOR of COVID-19 diagnosis decreased significantly with increasing commuting distance. The aORs of using public transportation to infection anxiety were 1.44 (95% CI: 1.31–1.59) (commuting time) and 1.45 (95% CI: 1.32–1.60) (commuting distance). The longer the commuting time, the more the aOR increased.

Conclusions
COVID-19 risk, close contact, and infection anxiety were all associated with the use of public transportation during commuting. Both commuting distance and time were associated with infection anxiety due to commuting, and the strength of the association increased with increase in commuting time distance. Since transportation by commuting is associated with COVID-19 risk and anxiety, we recommend the use of telecommuting and other means of work.
Electroencephalography-demonstrated mechanisms of dexmedetomidine-mediated deepening of propofol anesthesia: an observational study
Authors: Zhang Lei , Fang Kun , Tao Shengwei , Deng Liyun , Li Hua , Cao Yuanyuan , Wang Lei , Yu Fengqiong , Gu Erwei 
Published: December 2021

Abstract
Background
Although dexmedetomidine (Dex) is known to reduce bispectral index (BIS) values and propofol dosage, there is little information regarding raw electroencephalography (EEG) changes related to Dex deepening of propofol general anesthesia (GA). This study investigated the Dex effects on propofol GA via analysis of EEG changes.

Methods
A study cohort of 21 surgical patients (age range, 20–60 years) categorized as American Society of Anesthesiologists (ASA) class I or II was enrolled. We used time-varying spectral and bicoherence methods to compare electroencephalogram signatures 5 min before versus 10 min after intravenous Dex injection under propofol GA. The means and medians are reported with 95% confidence intervals (CIs) and inter-quartile ranges (IQRs), respectively.

Results
Dex augmented the slow waves power and theta (θ) oscillation bicoherence peak from a mean (95% CI) of 22.1% (19.0, 25.2) to 25.2% (21.8, 28.6). Meanwhile, Dex reduced alpha (α) peak power and bicoherence from 3.5 dB (1.0, 6.0) and 41.5% (34.0, 49.0) to 1.7 dB (− 0.6, 4.0) and 35.4% (29.0, 41.8), respectively, while diminishing the median frequency of α oscillation peak values and the mean frequency of α peaks in bicoherence spectra from 12.0 Hz (IQR 11.2, 12.6) and 11.7 Hz (11.3, 12.2) to 11.1 Hz (IQR 10.3, 11.8) and 11.2 Hz (10.9, 11.6), respectively.

Conclusions
Profound EEG changes support the supposition that Dex enhances propofol-induced GA from a moderate to a deeper state. The present findings provide a theoretical basis and reference regarding protocols aimed at reducing anesthetic/sedative dosage while maintaining sufficient depth of GA.

Clinical trial registration
ChiCTR, ChiCTR1900026955. Registered on 27 October 2019
PIG-A gene mutation as a genotoxicity biomarker in polycyclic aromatic hydrocarbon-exposed barbecue workers
Authors: Cao Yiyi , Xi Jing , Tang Chuanxi , Yang Ziying , Liu Weiying , You Xinyue , Feng Nannan , Zhang Xin Yu , Wu Jingui , Yu Yingxin , Luan Yang 
Published: December 2021

Abstract

Background

The PIG-A gene mutation assay is a valuable tool for measuring in vivo gene mutations in blood cells. The human PIG-A assay, used as a potential genotoxicity biomarker, is minimally invasive, sensitive, and cost-efficient; however, the relationship between carcinogen exposure and PIG-A mutations is not well understood.

Methods

We investigated the genotoxic effect of red blood cells using PIG-A assay and lymphocyte cytokinesis-block micronucleus test in barbecue restaurant workers (N = 70) exposed to polycyclic aromatic hydrocarbons (PAHs) and self-identified healthy control subjects (N = 56). Urinary PAH metabolites were measured to evaluate internal exposure levels.

Results

Multivariate Poisson regression showed that the PAH-exposed workers exhibited significantly higher PIG-A mutant frequency (MF) (8.04 ± 6.81 × 10− 6) than did the controls (5.56 ± 5.26 × 10− 6) (RR = 0.707, 95% CI: 0.615–0.812, P < 0.001). These results indicate that PAH exposure is a risk factor for elevated PIG-A MF. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in the PAH-exposed workers (MN: 3.06 ± 2.07 ‰, NBUD: 1.38 ± 1.02 ‰) were also significantly higher than in the controls (MN: 1.46 ± 0.64 ‰, P < 0.001; NBUD: 0.70 ± 0.60 ‰, P < 0.001). Additionally, PIG-A MFs showed better associations with several urinary hydroxylated PAH metabolites (P2-OH-Flu = 0.032, r2-OH-Flu = 0. 268; P2-OH-Phe = 0.022, r2-OH-Phe = 0.286; P3-OH-Phe = 0.0312, r3-OH-Phe = 0.270; P4-OH-Phe = 0.018, r4-OH-Phe = 0.296), while the increase in MN, NPB, and NBUD frequencies was not associated with any OH-PAH metabolites; and high-PAH-exposed workers showed the highest PIG-A MFs. Furthermore, there was a significant association between PIG-A MF and PAH exposure levels (Chi-square test for trend, P = 0.006).

Conclusions
Our results indicate that an increase in PIG-A MF in barbecue workers could reflect the response to PAH exposure, providing evidence of its potential as a genotoxicity biomarker in human risk assessment.
The Chinese path of integration and development among all ethnic groups from a comparative perspective between China and the west
Authors: Zhou Shaoqing 
Published: December 2021

AbstractBy comparing five aspects between China and the West—ideas, model of political participation, path of economic and social development, pattern of protection of language and culture rights, and construction of national cohesion and social (Minzu) solidarity, this paper reveals that the Chinese path of integration and development among all ethnic groups has the following characteristics: the ideas of equality, solidarity, mutual assistance and harmony among all ethnic groups; the integrative participation model of all ethnic groups under the unified leadership of the Communist Party of China; the integration on the economic and social development (common prosperity and development); equal protection of the language and culture rights of all ethnic groups; strong sense of national cohesion and social solidarity of fifty-six ethnic groups, based on the equal emphasis on the individual and collective rights as well as the close integration between political value and traditional cultural value. In general, China’s ethnic policies embody both specific rights and the level of community with a common future. Under the leadership of the Communist Party of China, relations between ethnic groups are harmonious and positive, and development of all ethnic groups tends to achieve a real equality. In Western countries, ethnic (or racial) relations remain relatively stable with fluctuations from time to time, and the development gap between ethnic groups has a trend of further expansion. Different ideas, systems and cultural concepts lead to different ethnic relationships and current situations of development between China and the West.
Gallium-68-somatostatin receptor PET/CT parameters as potential prognosticators for clinical time to progression after peptide receptor radionuclide therapy: a cohort study
Authors: Ebbers Sander C. , Heimgartner Muriël , Barentsz Maarten W. , van Leeuwaarde Rachel S. , van Treijen Mark J. C. , Lam Marnix M. E. G. , Braat Arthur J. A. T. 
Published: December 2021

Abstract
Background
Early [68Ga]Ga-DOTA-TOC PET/CT imaging after peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasm patients is often used as a prognosticator for survival, but lacks validity. This study investigates the prognostic value of changes in PET parameters after PRRT.

Methods
Baseline and follow-up [68Ga]Ga-DOTA-TOC PET/CT scans of all patients treated with PRRT were delineated automatically. Total lesion somatostatin receptor expression (TL-SSTR) and somatostatin receptor expressing tumor volume (SSTR-TV) were used as covariates in Cox proportional hazard models to predict time-to-new treatment.

Results
In twenty patients, median time-to-new treatment was 19.3 months (range [3.8; 36.2]). Absolute and percentual changes in both PET parameters were not associated with time-to-new treatment. A significant relation between independent baseline and follow-up SSTR-TV and follow-up TL-SSTR, and time-to-new treatment was identified.

Conclusions
Automatically derived [68Ga]Ga-DOTA-TOC PET/CT parameters are easy to acquire and may be of prognostic value after completing PRRT. Acquiring SSTR-TV or TL-SSTR parameters at baseline and during follow-up can be of value in identifying a patient’s prognosis.