bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 N Protein Induces Acute Lung Injury in Mice via NF-ĸB Activation
Authors: Xia Jie , Tang Wenqi , Wang Jiangmei , Lai Dengming , Xu Qi , Huang Ruoqiong , Hu Yaoqin , Gong Xiaojue , Fan Jiajie , Shu Qiang , Xu Jianguo 
Published: December 2021

BackgroundInfection of SARS-CoV-2 may cause acute respiratory syndrome. It has been reported that SARS-CoV-2 nucleocapsid protein (N-protein) presents early in body fluids during infection. The direct involvement of N-protein in lung injury is poorly understood.MethodsRecombinant N-protein was pretreated with polymyxin B, a lipopolysaccharide (LPS)-neutralizing agent. C57BL/6, C3H/HeJ (resistant to LPS), and C3H/HeN (control for C3H/HeJ) mice were exposed to N-protein via intratracheal administration to examine acute lung injury. In vitro, bone marrow–derived macrophages (BMDMs) were cultured with N-protein to study phosphorylation of nuclear factor kappa B (NF-ĸB) p65, macrophage polarization, and expression of proinflammatory cytokines.ResultsN-protein produced acute lung injury in C57BL/6 mice, with elevated protein permeability, total cell count, neutrophil infiltration, and proinflammatory cytokines in the bronchioalveolar lavage. N-protein also induced lung injury in both C3H/HeJ and C3H/HeN mice, indicating that the effect could not be attributed to the LPS contamination. N-protein triggered phosphorylation of NF-ĸB p65 in vitro, which was abolished by both N-protein denaturation and treatment with an antibody for N-protein, demonstrating that the effect is N-protein specific. In addition, N-protein promoted M1 macrophage polarization and the expression of proinflammatory cytokines, which was also blocked by N-protein denaturation and antibody for N-protein. Furthermore, N-protein induced NF-ĸB p65 phosphorylation in the lung, while pyrrolidine dithiocarbamate, an NF-ĸB inhibitor, alleviated the effect of N-protein on acute lung injury. ConclusionsSARS-CoV-2 N-protein itself is toxic and induces acute lung injury in mice. Both N-protein and NF-ĸB pathway may be therapeutic targets for treating multi-organ injuries in Coronavirus disease 2019 (COVID-19).
Integrated Knowledge Translation in Non-Communicable Disease Research in Sub-Saharan Africa: A Comparison of Systematic and Ad Hoc Stakeholder Engagement
Authors: Mpando Talitha L. , Sell Kerstin , Delobelle Peter , Osuret Jimmy , Niyibizi Jean Berchmans , Ntawuyirushintege Seleman , Geremew Bezinash , Jessani Nasreen S. 
Published: December 2021

BackgroundLow- and middle-income countries (LMICs) are currently experiencing an increasing prevalence of non-communicable diseases (NCDs). To address this as well as other health challenges, Integrated Knowledge Translation (IKT) approaches to build mutually beneficial relationships between researchers and decision-makers can concurrently inform research as well as enhance evidence use in policy and practice. The Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) is a research consortium which conducts research on NCDs and uses an IKT approach to facilitate the uptake of this research in five African countries: Ethiopia, Uganda, Rwanda, Malawi, and South Africa. Tailored IKT strategies were designed and implemented to plan and guide stakeholder engagement. This systematic approach contrasts with more commonly usedad hocapproaches to stakeholder engagement.MethodsIn this article, we explore the experiences of researchers engaged in the CEBHA+ IKT approach across the five African countries. Data sources included: 1) an informal document review of CEBHA+ country-specific IKT strategies, IKT team meeting minutes and activity reports, and 2) a semi-structured survey of IKT implementers to elicit country-specific experiences on actual implementation and adaptation of the IKT strategies. Results were collated and contrasted across all CEBHA+ countries with a focus on systematic versusad hocapproaches to engagement.ResultsSouth Africa, Malawi and Ethiopia country teams indicated that their engagements benefited from a systematic IKT strategy. This was especially the case in the early stages of the project as it allowed focused and intentional engagement. However,ad hocengagement was still required as new professional relationships developed, and contextual circumstances - including the SARS-CoV-2 pandemic - required responsive engagement with decision-makers and other stakeholders. In Rwanda and Uganda, continuous systematic engagement was found to bolster ownership of the research at both community and national levels.ConclusionPolitical and health climates are constantly shifting with a need to maintain flexibility in how IKT strategies are implemented. While strategic IKT can benefit from deliberate planning and stakeholder engagement, there is value in remaining flexible to respond to the needs of stakeholders and contextual circumstances. This paper highlights how IKT implementers in the five African CEBHA+ countries responded to this challenge.
Observation of Peripapillary Choroidal Vascularity in Natural Disease Course and After Gene Therapy for Leber's Hereditary Optic Neuropathy
Authors: Jiang Jingwen , Sun Gongpeng , Miao Qingmei , Li Bin , Wang Dan , Yuan Jiajia , Chen Changzheng 
Published: December 2021

Purpose: To compare peripapillary choroidal vascularity among Leber's Hereditary Optic Neuropathy (LHON) patients at different stages of natural course and healthy controls using optical coherence tomography (OCT), and to evaluate peripapillary choroidal vascularity changes in LHON patients before and after gene therapy.Methods: 57 LHON patients and 15 healthy controls were enrolled in this prospective clinical study. LHON patients were divided into three duration groups based on stage of disease progression. Both patients and healthy controls underwent OCT scans focused on the optic disc at baseline with Heidelberg Spectralis, and patients underwent OCT at 1, 3, and 6 months after gene therapy. OCT images were converted and binarized using ImageJ software. Choroidal thickness (CT), total choroidal area (TCA), and choroidal vascularity index (CVI) in each quadrant of OCT images were measured to evaluate peripapillary choroidal vascularity.Results: At baseline, the average CT was not significantly different between LHON patients at different stages and between healthy controls (P = 0.468). Although average TCA and average CVI were slightly higher in LHON patients at different stages than in healthy controls, the difference was not statistically significant (P = 0.282 and 0.812, respectively). After gene therapy, The average TCA at 1 month after gene therapy was significantly higher than that before gene therapy (P = 0.003), while no significant differences were found in the average CT or average CVI in LHON patients before and 1,3 and 6 months after gene therapy using pairwise comparisons (all P &gt; 0.05).Conclusions: No significant difference was found in choroidal vascularity of LHON patients at different stages and healthy controls. Choroidal vascularity seems to stay stable after gene therapy.
Comparison of Drug-Induced Sleep Endoscopy and Natural Sleep Endoscopy in the Assessment of Upper Airway Pathophysiology During Sleep: Protocol and Study Design
Authors: Van den Bossche Karlien , Van de Perck Eli , Wellman Andrew , Kazemeini Elahe , Willemen Marc , Verbraecken Johan , Vanderveken Olivier M. , Vena Daniel , Op de Beeck Sara 
Published: December 2021

Study Objectives: Obstructive sleep apnea (OSA) is increasingly recognized as a complex and heterogenous disorder. As a result, a “one-size-fits-all” management approach should be avoided. Therefore, evaluation of pathophysiological endotyping in OSA patients is emphasized, with upper airway collapse during sleep as one of the main features. To assess the site(s) and pattern(s) of upper airway collapse, natural sleep endoscopy (NSE) is defined as the gold standard. As NSE is labor-intensive and time-consuming, it is not feasible in routine practice. Instead, drug-induced sleep endoscopy (DISE) is the most frequently used technique and can be considered as the clinical standard. Flow shape and snoring analysis are non-invasive measurement techniques, yet are still evolving. Although DISE is used as the clinical alternative to assess upper airway collapse, associations between DISE and NSE observations, and associated flow and snoring signals, have not been quantified satisfactorily. In the current project we aim to compare upper airway collapse identified in patients with OSA using endoscopic techniques as well as flow shape analysis and analysis of tracheal snoring sounds between natural and drug-induced sleep.Methods: This study is a blinded prospective comparative multicenter cohort study. The study population will consist of adult patients with a recent diagnosis of OSA. Eligible patients will undergo a polysomnography (PSG) with NSE overnight and a DISE within 3 months. During DISE the upper airway is assessed under sedation by an experienced ear, nose, throat (ENT) surgeon using a flexible fiberoptic endoscope in the operating theater. In contrast to DISE, NSE is performed during natural sleep using a pediatric bronchoscope. During research DISE and NSE, the standard set-up is expanded with additional PSG measurements, including gold standard flow and analysis of tracheal snoring sounds.Conclusions: This project will be one of the first studies to formally compare collapse patterns during natural and drug-induced sleep. Moreover, this will be, to the authors' best knowledge, the first comparative research in airflow shape and tracheal snoring sounds analysis between DISE and NSE. These novel and non-invasive diagnostic methods studying upper airway mechanics during sleep will be simultaneously validated against DISE and NSE.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04729478.
Low-Frequency Repetitive Transcranial Magnetic Stimulation Restores Dynamic Functional Connectivity in Subcortical Stroke
Authors: Qin Yin , Liu Xiaoying , Guo Xiaoping , Liu Minhua , Li Hui , Xu Shangwen 
Published: December 2021

Background and Purpose: Strokes consistently result in brain network dysfunction. Previous studies have focused on the resting-state characteristics over the study period, while dynamic recombination remains largely unknown. Thus, we explored differences in dynamics between brain networks in patients who experienced subcortical stroke and the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on dynamic functional connectivity (dFC).Methods: A total of 41 patients with subcortical stroke were randomly divided into the LF-rTMS (n = 23) and the sham stimulation groups (n = 18). Resting-state functional MRI data were collected before (1 month after stroke) and after (3 months after stroke) treatment; a total of 20 age- and sex-matched healthy controls were also included. An independent component analysis, sliding window approach, and k-means clustering were used to identify different functional networks, estimate dFC matrices, and analyze dFC states before treatment. We further assessed the effect of LF-rTMS on dFCs in patients with subcortical stroke.Results: Compared to healthy controls, patients with stroke spent significantly more time in state I [p = 0.043, effect size (ES) = 0.64] and exhibited shortened stay in state II (p = 0.015, ES = 0.78); the dwell time gradually returned to normal after LF-rTMS treatment (p = 0.015, ES = 0.55). Changes in dwell time before and after LF-rTMS treatment were positively correlated with changes in the Fugl–Meyer Assessment for Upper Extremity (pr = 0.48, p = 0.028). Moreover, patients with stroke had decreased dFCs between the sensorimotor and cognitive control domains, yet connectivity within the cognitive control network increased. These abnormalities were partially improved after LF-rTMS treatment.Conclusion: Abnormal changes were noted in temporal and spatial characteristics of sensorimotor domains and cognitive control domains of patients who experience subcortical stroke; LF-rTMS can promote the partial recovery of dFC. These findings offer new insight into the dynamic neural mechanisms underlying effect of functional recombination and rTMS in subcortical stroke.Registration:http://www.chictr.org.cn/index.aspx, Unique.identifier: ChiCTR1800019452.
A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy
Authors: Ahlin Rebecca , Bergmark Karin , Bull Cecilia , Devarakonda Sravani , Landberg Rikard , Sigvardsson Ida , Sjöberg Fei , Skokic Viktor , Steineck Gunnar , Hedelin Maria 
Published: December 2021

Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study.Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&amp;draw=2&amp;rank=1).Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome.Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.
(+)-9-Trifluoroethoxy-α-Dihydrotetrabenazine as a Highly Potent Vesicular Monoamine Transporter 2 Inhibitor for Tardive Dyskinesia
Authors: Wang Wenyan , Du Guangying , Lin Shilan , Liu Jing , Yang Huijie , Yu Dawei , Ye Liang , Zou Fangxia , Wang Hongbo , Zhang Rui , Tian Jingwei 
Published: December 2021

Valbenazine and deutetrabenazine are the only two therapeutic drugs approved for tardive dyskinesia based on blocking the action of vesicular monoamine transporter 2 (VMAT2). But there exist demethylated inactive metabolism at the nine position for both them resulting in low availability, and CYP2D6 plays a major role in this metabolism resulting in the genetic polymorphism issue. 9-trifluoroethoxy-dihydrotetrabenazine (13e) was identified as a promising lead compound for treating tardive dyskinesia. In this study, we separated 13e via chiral chromatography and acquired R,R,R-13e [(+)-13e] and S,S,S-13e [(−)-13e], and we investigated their VMAT2-inhibitory activity and examined the related pharmacodynamics and pharmacokinetics properties using in vitro and in vivo models (+)-13e displayed high affinity for VMAT2 (Ki = 1.48 nM) and strongly inhibited [3H]DA uptake (IC50 = 6.11 nM) in striatal synaptosomes. Conversely, its enantiomer was inactive. In vivo, (+)-13e decreased locomotion in rats in a dose-dependent manner. The treatment had faster, stronger, and longer-lasting effects than valbenazine at an equivalent dose. Mono-oxidation was the main metabolic pathway in the liver microsomes and in dog plasma after oral administration, and glucuronide conjugation of mono-oxidized and/or demethylated products and direct glucuronide conjugation were also major metabolic pathways in dog plasma. O-detrifluoroethylation of (+)-13e did not occur. Furthermore, CYP3A4 was identified as the primary isoenzyme responsible for mono-oxidation and demethylation metabolism, and CYP2C8 was a secondary isoenzyme (+)-13e displayed high permeability across the Caco-2 cell monolayer, and it was not a P-glycoprotein substrate as demonstrated by its high oral absolute bioavailability (75.9%) in dogs. Thus, our study findings highlighted the potential efficacy and safety of (+)-13e in the treatment of tardive dyskinesia. These results should promote its clinical development.
A Randomized Controlled Trial of a Positive Family Holistic Health Intervention for Probationers in Hong Kong: A Mixed-Method Study
Authors: Lai Agnes Y.-K. , Sit Shirley M.-M. , Thomas Carol , Cheung George O.-C. , Wan Alice , Chan Sophia S.-C. , Lam Tai-hing 
Published: December 2021

Introduction: Probationers, offenders with less serious and non-violent offences, and under statutory supervision, have low levels of self-esteem and physical health, and high level of family conflict, and poorer quality of family relationships. This study examined the effectiveness of the existing probation service and the additional use of a positive family holistic health intervention to enhance physical, psychological, and family well-being in probationers and relationships with probation officers.Methods: Probationers under the care of the Hong Kong Social Welfare Department were randomized into a care-as-usual control group (CAU), a brief intervention group (BI) receiving two 1-h individual sessions [of a brief theory-based positive family holistic health intervention integrating Zero-time Exercise (simple and easy-to-do lifestyle-integrated physical activity) and positive psychology themes of “Praise and Gratitude” in the existing probation service], or a combined intervention group (CI) receiving BI and a 1-day group activity with family members. The outcomes were physical activity, fitness performance, self-esteem, happiness, anxiety and depression symptoms, life satisfaction, quality of life, family communication and well-being, and relationships with probation officers. Self-administered questionnaires and simple fitness tests were used at baseline, 1-month and 3-month follow-up. Linear mixed model analysis was used to compare difference in the changes of outcome variables among groups, adjusted of sex, age, and baseline values. Focus group interviews were conducted. Thematic content analysis was used.Results: 318 probationers (51% male) were randomized into CAU (n = 105), BI (n = 108), or CI (n = 105) group. CAU showed enhanced physical activity, fitness performance and psychological health, and family communication with small effect sizes (Cohen’s d: 0.19–0.41). BI and CI showed further improved physical activity, family communication and family well-being (Cohen’s d: 0.37–0.70). Additionally, CI reported greater improvements in the relationships with probation officers than CAU with a small effect size (Cohen’s d: 0.43). CI also reported greater increases in physical activity and family communication than BI with small to moderate effect sizes (Cohen’s d: 0.38–0.58). Qualitative feedbacks corroborated the quantitative findings.Conclusion: Our trial provided the first evidence of the effectiveness of probation service and the additional use of an innovative, relatively low-cost, theory-based brief positive family holistic health intervention. This intervention may offer a new model for enhancing probation service.Trial Registration: The research protocol was registered at the National Institutes of Health (identifier: NCT02770898).
Substance Use Disorders as a Critical Element for Decision-Making in Forensic Assertive Community Treatment: A Systematic Review
Authors: Marquant Thomas , Van Nuffel Meike , Sabbe Bernard , Goethals Kris 
Published: December 2021

Introduction:The prevalence of substance use disorders in forensic populations is high. They are an important factor linked to negative outcomes in mentally ill offenders and are detrimental to forensic or non-forensic outcome measures. In contrast, substance use disorders are often underdiagnosed and undertreated, especially in forensic settings. Forensic Assertive Community Treatment is a forensic adaptation of regular assertive community treatment, combined with essential elements of forensic rehabilitation theories. Little is known however on the effectivity of forensic assertive community treatment when it comes to substance use disorders or what their exact role is on the outcome measures. In this paper, we explore how SUD is treated in Forensic assertive community treatment and how it relates to the forensic and non-forensic outcome measures.Methods:We performed a systematic review (PRISMA) of forensic Assertive community treatment teams that followed the main evidence-based principles of regular assertive community treatment and added basic elements of forensic rehabilitation. We analyzed articles the Psychinfo and Medline databases dating from 2005 to 2020. Fifteen studies fit the search criteria and were included in the analysis. The Quality of the studies was assessed using the Newcastle-Ottawa scale.Results:SUD was highly prevalent in all studies. Patients entered FACT through two pathways, either from a care continuum or directly from prison. The severity of SUD at intake emerges as a critical element when deciding which pathway to choose, as a high severity-score at the start of FACT follow-up was linked to recidivism. While differing in method all studies offered integrated SUD treatment. These included evidence-based techniques like CBT, therapeutic communities, and Substance Abuse Management Module. Though results on SUD outcomes were mixed 4 studies mentioned abstinence in 50–75%. The severity of SUD tended to increase initially and to stabilize afterwards.Conclusion:Severity of SUD at intake emerges as a decisive element in decision-making on entering FACT teams directly from prison or through a care-continuum. The ways to provide SUD treatment varied and outcomes for SUD were mixed. SUD was found to be detrimental to forensic and non-forensic outcome measures, such as recidivism or hospitalizations during FACT treatment.