bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Integrated Deep Learning and Molecular Dynamics Simulation-Based Screening Pipeline Identifies Inhibitors of a New Cancer Drug Target TIPE2
Authors: Zhang Haiping , Li Junxin , Saravanan Konda Mani , Wu Hao , Wang Zhichao , Wu Du , Wei Yanjie , Lu Zhen , Chen Youhai H. , Wan Xiaochun , Pan Yi 
Published: November 2021

The TIPE2 (tumor necrosis factor-alpha-induced protein 8-like 2) protein is a major regulator of cancer and inflammatory diseases. The availability of its sequence and structure, as well as the critical amino acids involved in its ligand binding, provides insights into its function and helps greatly identify novel drug candidates against TIPE2 protein. With the current advances in deep learning and molecular dynamics simulation-based drug screening, large-scale exploration of inhibitory candidates for TIPE2 becomes possible. In this work, we apply deep learning-based methods to perform a preliminary screening against TIPE2 over several commercially available compound datasets. Then, we carried a fine screening by molecular dynamics simulations, followed by metadynamics simulations. Finally, four compounds were selected for experimental validation from 64 candidates obtained from the screening. With surprising accuracy, three compounds out of four can bind to TIPE2. Among them, UM-164 exhibited the strongest binding affinity of 4.97 µM and was able to interfere with the binding of TIPE2 and PIP2 according to competitive bio-layer interferometry (BLI), which indicates that UM-164 is a potential inhibitor against TIPE2 function. The work demonstrates the feasibility of incorporating deep learning and MD simulation in virtual drug screening and provides high potential inhibitors against TIPE2 for drug development.
Research Advances in Pharmacology, Safety, and Clinical Applications of Yunnan Baiyao, a Traditional Chinese Medicine Formula
Authors: Yao Qi , Chang Bo-tao , Chen Rong , Wei Yi-jing , Gong Qiu-ju , Yu Dan , Zhang Yang , Han Xu , Yang Hong-bo , Tang Song-jiang , Gao Ying 
Published: November 2021

Ethnopharmacology relevance: Yunnan Baiyao (YNBY), a traditional Chinese medicine formulae, has some significant properties including activating blood circulation to dissipate blood stasis (Huo-Xue-Hua-Yu), eliminating swelling and alleviating pain (Xiao-Zhong-Zhi-Tong), and eliminating necrotic tissues and promoting granulation (Qu-Fu-Sheng-Ji).Aim of this study: This paper intends to provide a comprehensive and critical analysis of studies on YNBY, proposing new possible therapeutic directions of this formula.Materials and methods: Relevant data on YNBY were retrieved from available databases and a hand-search by searching the keywords such as “Yunnan Baiyao,” “pharmacology,” “toxicity,” and “clinical applications.”Results: Traditionally, YNBY has been used to cure hemorrhage, bruises, swelling, and pain caused by injuries in the Chinese folk. Modern pharmacological studies show that YNBY possesses pharmacological activities including hemostasis, invigorating the circulation of blood, wound healing, anti-inflammation, analgesia, antibiosis, infection prevention, and other effects. Toxicological studies demonstrate that YNBY has a certain toxicology, which is mainly caused by Aconitum alkaloids from Cao-wu (CW, Aconiti Kusnezoffii Radix). The developmental non-toxic reaction dose (NOAEL) of YNBY for embryos and fetuses is 0.5 g/kg in rats. In addition, the NOAEL for fertility and early embryo development toxicity is 4.0 g/kg in rats. Clinical trials have confirmed the safety of YNBY in a large number of patients, and adverse drug reactions (ADRs) such as abdominal pain, diarrhea, allergy, and others in very few people. YNBY is routinely used in clinic to cure bleeding, pain, swelling, upper digestive tract ulcer, postoperative wound, arthritis, mouth ulcers, ulcerative colitis, etc.Conclusions: Hemostasis is a conspicuous effect of YNBY. Except for this effect, analgesia and anti-infection may be new research directions of this formula. In addition, the in vitro and in vivo pharmacology and mechanisms of action of YNBY are encouraged as well as the pharmacokinetics of this formulae. Furthermore, the material basis of the pharmacological effects of YNBY also needs clear identification.
Thoracic Outlet Syndrome: Fingertip Cannot Replace Forearm Photoplethysmography in the Evaluation of Positional Venous Outflow Impairments
Authors: Hersant Jeanne , Ramondou Pierre , Durand Sylvain , Feuilloy Mathieu , Daligault Mickael , Abraham Pierre , Henni Samir 
Published: November 2021

Objective: Fingertip photoplethysmography (PPG) resulting from high-pass filtered raw PPG signal is often used to record arterial pulse changes in patients with suspected thoracic outlet syndrome (TOS). Results from venous (low-pass filtered raw signal) forearm PPG (V-PPG) during the Candlestick-Prayer (Ca + Pra) maneuver were recently classified into four different patterns in patients with suspected TOS, two of which are suggestive of the presence of outflow impairment. We aimed to test the effect of probe position (fingertip vs. forearm) and of red (R) vs. infrared (IR) light wavelength on V-PPG classification and compared pattern classifications with the results of ultrasound (US).Methods: In patients with suspected TOS, we routinely performed US imaging (US + being the presence of a positional compression) and Ca + Pra tests with forearm V-PPGIR. We recruited patients for a Ca + Pra maneuver with the simultaneous fingertip and forearm V-PPGR. The correlation of each V-PPG recording to each of the published pattern profiles was calculated. Each record was classified according to the patterns for which the coefficient of correlation was the highest. Cohen’s kappa test was used to determine the reliability of classification among forearm V-PPGIR, fingertip V-PPGR, and forearm V-PPGR.Results: We obtained 40 measurements from 20 patients (40.2 ± 11.3 years old, 11 males). We found 13 limbs with US + results, while V-PPG suggested the presence of venous outflow impairment in 27 and 20 limbs with forearm V-PPGIR and forearm V-PPGR, respectively. Fingertip V-PPGR provided no patterns suggesting outflow impairment.Conclusion: We found more V-PPG patterns suggesting venous outflow impairment than US + results. Probe position is essential if aiming to perform upper-limb V-PPG during the Ca + Pra maneuver in patients with suspected TOS. V-PPG during the Ca + Pra maneuver is of low cost and easy and provides reliable, recordable, and objective evidence of forearm swelling. It should be performed on the forearm (close to the elbow) with either PPGR or PPGIR but not at the fingertip level.
The Effects of Tai Chi and Qigong Exercise on Psychological Status in Adolescents: A Systematic Review and Meta-Analysis
Authors: Liu Xuan , Li Ru , Cui Jiabao , Liu Fang , Smith Lee , Chen Xiaorong , Zhang Debao 
Published: November 2021

Background: The purpose of this study was to systematically review the effectiveness of Tai Chi and Qigong exercise on adolescents' symptoms of depression and anxiety, and psychological status based on clinical evidences, and to calculate the pooled results using meta-analysis.Methods: A systematic search using seven English and three Chinese databases was initiated to identify randomized controlled trials (RCT) and non-randomized comparison studies (NRS) assessing the effect of Tai Chi and Qigong exercise on psychological status among adolescents. Standardized mean differences (SMD) and their 95% confidence intervals (CI) were used to determine the pooled effect of the intervention. Study quality was evaluated using a Checklist to Evaluate a Report of a Non-pharmacological Trial (CLEAR-NPT) designed for non-pharmacological trials.Results: Four RCTs and six NRS were identified, including 1,244 adolescents. The results suggested a potential beneficial effect of Tai chi and Qigong exercise on reducing anxiety (SMD = 0.386, 95 CI% [0.233, 0.538]) and depression (SMD = 1.937 [95 CI%, 1.392–2.546]) symptoms, and reducing cortisol level (SMD = 0.621 [95 CI%, 0.18–1.062]) in adolescents. Conversely, non-significant effects were found for stress, mood, and self-esteem.Conclusions: The findings of this review suggest Qigong appears to be an effective therapeutic modality to improve psychological well-being in adolescents. Hope future studies will have rigorously designed, well-controlled randomized trials with large sample sizes in order to confirm these findings.
Implementation and Evaluation of Therapeutic Online Coaching Using Habit Reversal Training in Children With Tourette’s Disorder – A Pilot Study
Authors: Viefhaus Paula , Adam Julia , Goletz Hildegard , Woitecki Katrin , Döpfner Manfred 
Published: November 2021

Cognitive-behavioral interventions can be difficult to implement in daily routine, which is often essential for generalizing treatment effects to natural settings. Furthermore, there is a lack of adequate care options concerning habit reversal training for children with Tourette’s disorder. The objective of this study is to evaluate therapeutic online coachingviavideoconferencing in the natural environment of children with Tourette’s disorder in addition to face-to-face therapy (blended therapy). Online coaching took place twice a week for a maximum of 12 weeks. In a single-case study (n= 5; patients aged 8–11 years), the first results were obtained for exploratory purposes, especially with regard to the feasibility and reduction of symptoms and impairment. Various outcome measures were assessed (severity of symptoms, impairment, practical implementation, and satisfaction). Despite some principal limitations, the findings provide first hints that blended therapy is feasible and improves symptoms in some children with tics.Clinical Trial Registration:[https://clinicaltrials.gov/], identifier [DRKS00017199].
Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review
Authors: Raanes Emilie F. W. , Stiles Tore C. 
Published: November 2021

Background: Little emphasis has been given to the fact that various psychological processes and behaviors in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have neural correlates that affect—and are affected by—the immune system. The aim of this paper is to provide a systematic review of the literature on cross-sectional and longitudinal associations between psychological and immunological variables/changes in CFS/ME.Methods: The systematic literature search was conducted on Dec 10, 2020 using PubMed. Original research studies investigating associations between a predefined set of psychological and immunological variables in CFS/ME were included. Specifically, the review was focused on studies examining the following psychological variables: executive function, emotion regulation, interpersonal function, sleep, mental health, anxiety, depression, and/or other psychiatric symptoms. In terms of immunological variables, studies investigating interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor (TNF), CD4+, and/or CD8+ were included. Besides original research papers, other potentially relevant papers (e.g., literature reviews) were carefully read and reference lists were checked in order to identify any additional relevant studies. Available data was summarized in text and tables.Results: The literature search identified 897 potentially relevant papers. Ultimately, 14 studies (807 participants in total) were included in the review of which only two were longitudinal in nature. The review indicated that executive function is associated with IL-1 and IL-6, and interpersonal function is associated with IL-6 and TNF-α. Further, the available data suggested that emotion regulation is associated with IL-2 and sleep is associated with IL-1, IL-6, TNF-α, and IL-2. Interestingly, poorer emotion regulation, interpersonal function, and sleep have all been found to be associated with higher cytokine levels. Executive function has shown both positive and negative relationships with cytokines and among these psychological constructs, it is also the only one that has been found to be associated with CD4+ and CD8+ counts/percentages.Conclusions: Correlations exist between psychological and immunological variables in CFS/ME. However, there are few consistent findings and there is almost a complete lack of longitudinal studies. This review points to a gap in existing CFS/ME research and hopefully, it will inspire to the generation of innovative, psychoneuroimmunological hypotheses within the CFS/ME research field.
A Family-Focused Intervention for Parental Mental Illness: A Practitioner Perspective
Authors: Furlong Mairead , Mulligan Christine , McGarr Sharon , O'Connor Siobhan , McGilloway Sinead 
Published: November 2021

Background: Parental mental illness (PMI) is common and can lead to children developing mental disorders. Family Talk (FT) is a well-known and widely implemented intervention designed to reduce the risk of transgenerational psychopathology. However, given the research to practise “gap,” very little qualitative research, to date, has investigated practitioner experiences in implementing FT. This study aimed to explore the practitioner-perceived barriers and facilitators to the implementation and sustainability of FT within mainstream mental health settings.Methods: This qualitative study was nested within a randomised controlled trial (RCT) of Family Talk [N = 86 families (139 parents, 221 children)] within 15 adult (AMHS), child (CAMHS), primary care mental health, and child protection sites in Ireland. Semi-structured interviews and focus groups were undertaken with a purposive sample of clinicians (n = 31) and managers (n = 10), based on their experiences of implementing FT. Interview data were transcribed verbatim, analysed using constructivist grounded theory, and informed by Fixsen's implementation science framework.Results: Service providers highlighted a number of benefits for approximately two thirds of families across different diagnoses and mental health settings (AMHS/CAMHS/primary care). Sites varied in their capacity to embed FT, with key enablers identified as acquiring managerial and organisational support, building clinician skill, and establishing interagency collaboration. Implementation challenges included: recruitment difficulties, stresses in working with multiply-disadvantaged families, disruption in delivery due to the COVID-19 global pandemic, and sustainability concerns (e.g., perceived fit of FT with organisational remit/capacity, systemic and cultural barriers to change).Conclusion: This study is only the second qualitative study ever conducted to explore practitioner experiences in implementing FT, and the first conducted within the context of an RCT and national research programme to introduce family-focused practise (FFP) for families living with PMI. The findings illuminate the successes and complexities of implementing FFP in a country without a “think family” infrastructure, whilst highlighting a number of important generalisable lessons for the implementation of FT, and other similar interventions, elsewhere.
Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews
Authors: Hart Xenia M. , Eichentopf Luzie , Lense Xenija , Riemer Thomas , Wesner Katja , Hiemke Christoph , Gründer Gerhard 
Published: November 2021

Background: For many psychotropic drugs, monitoring of drug concentrations in the blood (Therapeutic Drug Monitoring; TDM) has been proven useful to individualize treatments and optimize drug effects. Clinicians hereby compare individual drug concentrations to population-based reference ranges for a titration of prescribed doses. Thus, established reference ranges are pre-requisite for TDM. For psychotropic drugs, guideline-based ranges are mostly expert recommendations derived from a conglomerate of cohort and cross-sectional studies. A systematic approach for identifying therapeutic reference ranges has not been published yet. This paper describes how to search, evaluate and grade the available literature and validate published therapeutic reference ranges for psychotropic drugs.Methods/Results: Following PRISMA guidelines, relevant databases have to be systematically searched using search terms for the specific psychotropic drug, blood concentrations, drug monitoring, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The search should be restricted to humans, and diagnoses should be pre-specified. Therapeutic references ranges will not only base upon studies that report blood concentrations in relation to clinical effects, but will also include implications from neuroimaging studies on target engagement. Furthermore, studies reporting concentrations in representative patient populations are used to support identified ranges. Each range will be assigned a level of underlying evidence according to a systematic grading system.Discussion: Following this protocol allows a comprehensive overview of TDM literature that supports a certain reference range for a psychotropic drug. The assigned level of evidence reflects the validity of a reported range rather than experts' opinions.
Global Burden of Respiratory Diseases Attributable to Ambient Particulate Matter Pollution: Findings From the Global Burden of Disease Study 2019
Authors: Wu Ying , Song Ping , Lin Shuai , Peng Ling , Li Yizhen , Deng Yujiao , Deng Xinyue , Lou Weiyang , Yang Si , Zheng Yi , Xiang Dong , Hu Jingjing , Zhu Yuyao , Wang Meng , Zhai Zhen , Zhang Dai , Dai Zhijun , Gao Jie 
Published: November 2021

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019.Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years.Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged &lt; 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP.Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.
Application of SARS-CoV-2 Serology to Address Public Health Priorities
Authors: Sherman Amy C. , Smith Teresa , Zhu Yerun , Taibl Kaitlin , Howard-Anderson Jessica , Landay Taylor , Pisanic Nora , Kleinhenz Jennifer , Simon Trevor W. , Espinoza Daniel , Edupuganti Neena , Hammond Skyler , Rouphael Nadine , Shen Huifeng , Fairley Jessica K. , Edupuganti Srilatha , Cardona-Ospina Jaime A. , Rodriguez-Morales Alfonso J. , Premkumar Lakshmanane , Wrammert Jens , Tarleton Rick , Fridkin Scott , Heaney Christopher D. , Scherer Erin M. , Collins Matthew H. 
Published: November 2021

Background: Antibodies against SARS-CoV-2 can be detected by various testing platforms, but a detailed understanding of assay performance is critical.Methods: We developed and validated a simple enzyme-linked immunosorbent assay (ELISA) to detect IgG binding to the receptor-binding domain (RBD) of SARS-CoV-2, which was then applied for surveillance. ELISA results were compared to a set of complimentary serologic assays using a large panel of clinical research samples.Results: The RBD ELISA exhibited robust performance in ROC curve analysis (AUC&gt; 0.99; Se = 89%, Sp = 99.3%). Antibodies were detected in 23/353 (6.5%) healthcare workers, 6/9 RT-PCR-confirmed mild COVID-19 cases, and 0/30 non-COVID-19 cases from an ambulatory site. RBD ELISA showed a positive correlation with neutralizing activity (p = &lt;0.0001, R2 = 0.26).Conclusions: We applied a validated SARS-CoV-2-specific IgG ELISA in multiple contexts and performed orthogonal testing on samples. This study demonstrates the utility of a simple serologic assay for detecting prior SARS-CoV-2 infection, particularly as a tool for efficiently testing large numbers of samples as in population surveillance. Our work also highlights that precise understanding of SARS-CoV-2 infection and immunity at the individual level, particularly with wide availability of vaccination, may be improved by orthogonal testing and/or more complex assays such as multiplex bead assays.
SNP and Phylogenetic Characterization of Low Viral Load SARS-CoV-2 Specimens by Target Enrichment
Authors: Orf Gregory S. , Forberg Kenn , Meyer Todd V. , Mowerman Illya , Mohaimani Aurash , Faron Matthew L. , Jennings Cheryl , Landay Alan L. , Goldstein D. Yitz , Fox Amy S. , Berg Michael G. , Cloherty Gavin A. 
Published: November 2021

Background: Surveillance of SARS-CoV-2 across the globe has enabled detection of new variants and informed the public health response. With highly sensitive methods like qPCR widely adopted for diagnosis, the ability to sequence and characterize specimens with low titers needs to keep pace.Methods: Nucleic acids extracted from nasopharyngeal swabs collected from four sites in the United States in early 2020 were converted to NGS libraries to sequence SARS-CoV-2 genomes using metagenomic and xGen target enrichment approaches. Single nucleotide polymorphism (SNP) analysis and phylogeny were used to determine clade assignments and geographic origins of strains.Results: SARS-CoV-2-specific xGen enrichment enabled full genome coverage for 87 specimens with Ct values &lt;29, corresponding to viral loads of &gt;10,000 cp/ml. For samples with viral loads between 103 and 106 cp/ml, the median genome coverage for xGen was 99.1%, sequence depth was 605X, and the “on-target” rate was 57 ± 21%, compared to 13%, 2X and 0.001 ± 0.016%, respectively, for metagenomic sequencing alone. Phylogenetic analysis revealed the presence of most clades that existed at the time of the study, though clade GH dominated in the Midwest.Conclusions: Even as vaccines are being widely distributed, a high case load of SARS-CoV-2 infection persists around the world. Viral genetic surveillance has succeeded in warning the public of new variants in circulation and ensured that diagnostic tools remain resilient to a steadily increasing number of mutations. Target capture offers a means of characterizing low viral load samples which would normally pose a challenge for metagenomic sequencing.