bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceived satisfaction with HIV care and its association with adherence to antiretroviral therapy and viral suppression in the African Cohort Study
Authors: Somi Nancy , Dear Nicole , Reed Domonique , Parikh Ajay , Lwilla Anange , Bahemana Emmanuel , Khamadi Samoel , Iroezindu Michael , Kibuuka Hannah , Maswai Jonah , Crowell Trevor A. , Owuoth John , Maganga Lucas , Polyak Christina , Ake Julie , Esber Allahna ,   the AFRICOS Study Group
Published: November 2021

Abstract
Background
Increased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression.

Methods
The African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load < 1000 copies/mL).

Results
As of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97–1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00–1.16).

Conclusions
While patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.
Home-based (virtual) rehabilitation improves motor and cognitive function for stroke patients: a randomized controlled trial of the Elements (EDNA-22) system
Authors: Wilson Peter H. , Rogers Jeffrey M. , Vogel Karin , Steenbergen Bert , McGuckian Thomas B. , Duckworth Jonathan 
Published: November 2021

Abstract
Background
Home-based rehabilitation of arm function is a significant gap in service provision for adult stroke. The EDNA-22 tablet is a portable virtual rehabilitation-based system that provides a viable option for home-based rehabilitation using a suite of tailored movement tasks, and performance monitoring via cloud computing data storage. The study reported here aimed to compare use of the EDNA system with an active control (Graded Repetitive Arm Supplementary Program—GRASP training) group using a parallel RCT design.

Methods
Of 19 originally randomized, 17 acute-care patients with upper-extremity dysfunction following unilateral stroke completed training in either the treatment (n = 10) or active control groups (n = 7), each receiving 8-weeks of in-home training involving 30-min sessions scheduled 3–4 times weekly. Performance was assessed across motor, cognitive and functional behaviour in the home. Primary motor measures, collected by a blinded assessor, were the Box and Blocks Task (BBT) and 9-Hole Pegboard Test (9HPT), and for cognition the Montreal Cognitive Assessment (MoCA). Functional behaviour was assessed using the Stroke Impact Scale (SIS) and Neurobehavioural Functioning Inventory (NFI).

Results
One participant from each group withdrew for personal reasons. No adverse events were reported. Results showed a significant and large improvement in performance on the BBT for the more-affected hand in the EDNA training group, only (g = 0.90). There was a mild-to-moderate effect of training on the 9HPT for EDNA (g = 0.55) and control (g = 0.42) groups, again for the more affected hand. In relation to cognition, performance on the MoCA improved for the EDNA group (g = 0.70). Finally, the EDNA group showed moderate (but non-significant) improvement in functional behaviour on the SIS (g = 0.57) and NFI (g = 0.49).

Conclusion
A short course of home-based training using the EDNA-22 system can yield significant gains in motor and cognitive performance, over and above an active control training that also targets upper-limb function. Intriguingly, these changes in performance were corroborated only tentatively in the reports of caregivers. We suggest that future research consider how the implementation of home-based rehabilitation technology can be optimized. We contend that self-administered digitally-enhanced training needs to become part of the health literacy of all stakeholders who are impacted by stroke and other acquired brain injuries.
Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001557123. Registered 12 November 2019, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378298&isReview=true
Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
Authors: Shin Tae Hwan , Manavalan Balachandran , Lee Da Yeon , Basith Shaherin , Seo Chan , Paik Man Jeong , Kim Sang-Wook , Seo Haewoon , Lee Ju Yeon , Kim Jin Young , Kim A Young , Chung Jee Min , Baik Eun Joo , Kang Seong Ho , Choi Dong-Kug , Kang Yup , Mouradian M. Maral , Lee Gwang 
Published: November 2021

AbstractBackgroundNanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue.MethodsHere the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network.ResultsIntracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus.ConclusionsCombination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity.Graphical Abstract
Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma
Authors: Yang Jiawei , Zhang Mingxu , Song Qiuyi , Li Siqi , Zhao Xiulan , Kan Liping , Zhu Siquan 
Published: November 2021

AbstractBackgroundTraditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism.MethodsNetwork pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation.ResultsThe results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma.ConclusionBy combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.
Landscape of transcription termination in Arabidopsis revealed by single-molecule nascent RNA sequencing
Authors: Mo Weipeng , Liu Bo , Zhang Hong , Jin Xianhao , Lu Dongdong , Yu Yiming , Liu Yuelin , Jia Jinbu , Long Yanping , Deng Xian , Cao Xiaofeng , Guo Hongwei , Zhai Jixian 
Published: November 2021

Abstract
Background
The dynamic process of transcription termination produces transient RNA intermediates that are difficult to distinguish from each other via short-read sequencing methods.

Results
Here, we use single-molecule nascent RNA sequencing to characterize the various forms of transient RNAs during termination at genome-wide scale in wildtype Arabidopsis and in atxrn3, fpa, and met1 mutants. Our data reveal a wide range of termination windows among genes, ranging from ~ 50 nt to over 1000 nt. We also observe efficient termination before downstream tRNA genes, suggesting that chromatin structure around the promoter region of tRNA genes may block pol II elongation. 5′ Cleaved readthrough transcription in atxrn3 with delayed termination can run into downstream genes to produce normally spliced and polyadenylated mRNAs in the absence of their own transcription initiation. Consistent with previous reports, we also observe long chimeric transcripts with cryptic splicing in fpa mutant; but loss of CG DNA methylation has no obvious impact on termination in the met1 mutant.

Conclusions
Our method is applicable to establish a comprehensive termination landscape in a broad range of species.
Exploring reasons for recruitment failure in clinical trials: a qualitative study with clinical trial stakeholders in Switzerland, Germany, and Canada
Authors: Briel Matthias , Elger Bernice S. , McLennan Stuart , Schandelmaier Stefan , von Elm Erik , Satalkar Priya 
Published: November 2021

Abstract
Background
Poor participant recruitment is the most frequent reason for premature discontinuation of randomized clinical trials (RCTs), particularly if they are investigator-initiated. The aims of this qualitative study were to investigate (1) the views of clinical trial stakeholders from three different countries regarding reasons for recruitment failure in RCTs and (2) how these compare and contrast with the causes identified in a previous systematic review of RCT publications.

Methods
From August 2015 to November 2016, we conducted 49 semi-structured interviews with a purposive sample of clinical trial stakeholders. This included investigators based in Germany (n = 9), Switzerland (n = 6) and Canada (n = 1) with personal experience of a discontinued RCT and 33 other stakeholders (e.g., representatives of ethics committees, clinical trial units, pharmaceutical industry) in Switzerland. Individual semi-structured qualitative interviews were conducted and analyzed using thematic analysis.

Results
Interviewees identified a total of 29 different reasons for recruitment failure. Overoptimistic recruitment estimates, too narrow eligibility criteria, lack of engagement of recruiters/trial team, lack of competence/training/experience of recruiters, insufficient initial funding, and high burden for trial participants were mentioned most frequently. The interview findings largely confirm the previous systematic review on published reasons for recruitment failure. However, eight new reasons for recruitment failure were identified in the interviews, which led to the checklist of reasons for recruitment failure being revised and a new category describing research environment-related factors being added.

Conclusions
This study highlights the diversity of often interlinked reasons for recruitment failure in RCTs. Integrating the findings of this interview study with a previous systematic review of RCT publications led to a comprehensive, structured checklist of empirically-informed reasons for recruitment failure. The checklist may be useful to guide further research on interventions to improve participant recruitment in RCTs and helpful for trial investigators, research ethics committees, and funding agencies when assessing trial feasibility with respect to recruitment.
A core outcome set for clinical trials of first- and second-degree perineal tears prevention and treatment: a study protocol for a systematic review and a Delphi survey
Authors: Xiao Lin , Shi Lei , Liu Suting , Luo Yuanyuan , Tian Jinhui , Zhang Lili 
Published: November 2021

Abstract
Background
Perineal tear is a common consequence of vaginal births affecting females globally. Even mild perineal tears could cause short- and long-term complications for females. Though many studies of interventions to prevent or treat perineal tears to minimize the consequences have been conducted, there is a significant heterogeneity in the outcomes measured and reported in existing studies, which makes meaningful comparison difficult and makes the generalizability to clinical practice challenging. Developing a core outcome set (COS) could solve these methodological concerns. In this paper, we report a protocol to develop a COS for clinical trials of mild perineal tears, which shall assist in establishing the evidence base and implementation of effective measures to reduce the incidence and minimize the consequences of mild perineal tears.

Methods/design
The development of this COS will be guided by a study advisory group composed of obstetricians, midwives, nursing managers, service users, and methodologists. This study will include four stages: (1) a systematic research of the literature to identify outcomes reported in prior studies, (2) a semi-structured interview with key stakeholders to collect their opinions on important outcomes, (3) a panel of experts will be invited to conduct a three-round Delphi survey to prioritize these outcomes, and (4) a consensus meeting with key stakeholders to determine the list of outcomes included in the final COS.

Discussion
The development of this COS will provide international standards for the outcomes to be collected and reported in all clinical trials and audits of practice, which involve prevention and treatment of first- and second-degree perineal tears for women with vaginal delivery. This will facilitate comparing and contrasting of studies and allow for combining of appropriate studies with the ultimate goal of improved perineal care for women choosing vaginal delivery.

Trial registration
This study was registered in the database of Core Outcome Measures in Effectiveness Trials (COMET) on June11th, 2021 (https://comet-initiative.org/Studies/Details/1884).
Two weeks of twice-daily prism adaptation treatment does not improve posture or gait in Parkinson’s disease: a double-blind randomized controlled trial
Authors: Bultitude Janet H. , Pidgeon Dawna M. , LeBlanc Pauline R. , Jeffreys Charlotte A. , Alexandre Faith P. , Lee Stephen L. 
Published: November 2021

Abstract
Background
Gait difficulties in Parkinson’s disease have been related to problems shifting the center of gravity forward. We previously showed reduced forward stepping latencies for people with Parkinson’s disease after one session of adaptation to upward visual shifts, which produces downward motor after-effects and potentially shifts the center of gravity forward. Here we tested if repeated prism adaptation improved gait and postural control in Parkinson’s disease through a parallel, double-blind, randomized, sham-controlled trial.

Methods
We recruited participants with idiopathic Parkinson’s disease aged 40–85 and meeting any one of three clinical criteria: (1) Hoehn and Yahr Stage II.5–IV; (2) scoring > 0 on the gait, freezing of gait, and/or postural stability items of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; or (3) Timed Up and Go > 12 s. Sealed envelope style randomization allocated participants to two weeks of twice-daily prism adaptation or sham treatment. Participants, care givers, and those assessing the outcomes were blinded to group assignment. Primary outcomes were changes in postural control measured using the Berg Balance Scale and the Limits of Stability, Sensory Organization, and Motor Control tests from the Smart EquiTest system. Secondary outcomes included other physiotherapy and questionnaire measures. Outcomes were assessed at the Dartmouth Hitchcock Medical Center immediately before and after the treatment period, with further long-term postal follow-up over 3 months. Outcomes were analyzed using analyses of variance with follow-up t tests.

Results
Eighteen participants were allocated to undergo prism adaptation, of which sixteen were analyzed. Thirteen participants were allocated to undergo sham treatment, and all were analyzed. The prism adaptation group showed increased forward stepping velocity on the Limits of Stability test (pre: M=2.33, SEM=0.24; post: M=2.88, SEM=0.26; t(15)=3.2, p=.005, d=.819). The sham group showed no such change (pre: M=2.13, SEM=0.22; 1d post: M=2.24, SEM=0.22; t(13)=.636, p=.537, d=.176). However, there were no group differences for any other outcome measures and no indications that prism adaptation produced functional improvements in posture, gait, or activities of daily living.

Conclusions
Prism adaptation does not improve gait or postural control in Parkinson’s disease.

Trial registration
ClinicalTrials.govNCT02380859. Registered prospectively on 5 March 2015.
Cellulosic ethanol production by consortia of Scheffersomyces stipitis and engineered Zymomonas mobilis
Authors: Sun Lingling , Wu Bo , Zhang Zengqin , Yan Jing , Liu Panting , Song Chao , Shabbir Samina , Zhu Qili , Yang Shihui , Peng Nan , He Mingxiong , Tan Furong 
Published: November 2021

Abstract
Background
As one of the clean and sustainable energies, lignocellulosic ethanol has achieved much attention around the world. The production of lignocellulosic ethanol does not compete with people for food, while the consumption of ethanol could contribute to the carbon dioxide emission reduction. However, the simultaneous transformation of glucose and xylose to ethanol is one of the key technologies for attaining cost-efficient lignocellulosic ethanol production at an industrial scale. Genetic modification of strains and constructing consortia were two approaches to resolve this issue. Compared with strain improvement, the synergistic interaction of consortia in metabolic pathways should be more useful than using each one separately.

Results
In this study, the consortia consisting of suspended Scheffersomyces stipitis CICC1960 and Zymomonas mobilis 8b were cultivated to successfully depress carbon catabolite repression (CCR) in artificially simulated 80G40XRM. With this strategy, a 5.52% more xylose consumption and a 6.52% higher ethanol titer were achieved by the consortium, in which the inoculation ratio between S. stipitis and Z. mobilis was 1:3, compared with the Z. mobilis 8b mono-fermentation. Subsequently, one copy of the xylose metabolic genes was inserted into the Z. mobilis 8b genome to construct Z. mobilis FR2, leading to the xylose final-consumption amount and ethanol titer improvement by 15.36% and 6.81%, respectively. Finally, various corn stover hydrolysates with different sugar concentrations (glucose and xylose 60, 90, 120 g/L), were used to evaluate the fermentation performance of the consortium consisting of S. stipitis CICC1960 and Z. mobilis FR2. Fermentation results showed that a 1.56–4.59% higher ethanol titer was achieved by the consortium compared with the Z. mobilis FR2 mono-fermentation, and a 46.12–102.14% higher ethanol titer was observed in the consortium fermentation when compared with the S. stipitis CICC1960 mono-fermentation. Furthermore, qRT-PCR analysis of xylose/glucose transporter and other genes responsible for CCR explained the reason why the initial ratio inoculation of 1:3 in artificially simulated 80G40XRM had the best fermentation performance in the consortium.

Conclusions
The fermentation strategy used in this study, i.e., using a genetically modified consortium, had a superior performance in ethanol production, as compared with the S. stipitis CICC1960 mono-fermentation and the Z. mobilis FR2 mono-fermentation alone. This result showed that this strategy has potential for future lignocellulosic ethanol production.
The role of TGF-β or BMPR2 signaling pathway-related miRNA in pulmonary arterial hypertension and systemic sclerosis
Authors: Xu Bei , Xu Guanhua , Yu Ye , Lin Jin 
Published: November 2021

AbstractPulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD), causing death in systemic sclerosis (SSc). The past decade has yielded many scientific insights into microRNA (miRNAs) in PAH and SSc. This growth of knowledge has well-illustrated the complexity of microRNA (miRNA)-based regulation of gene expression in PAH. However, few miRNA-related SSc-PAH were elucidated. This review firstly discusses the role of transforming growth factor-beta (TGF-β) signaling and bone morphogenetic protein receptor type II (BMPR2) in PAH and SSc. Secondly, the miRNAs relating to TGF-β and BMPR2 signaling pathways in PAH and SSc or merely PAH were subsequently summarized. Finally, future studies might develop early diagnostic biomarkers and target-oriented therapeutic strategies for SSc-PAH and PAH treatment.