bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontier and hotspot evolution in Wiskott–Aldrich syndrome: A bibliometric analysis from 2001 to 2021
Authors: Liu Shixu , Yao Xiaoyan , Xia Kun , Zhang Jinzhi , Liu Yanyi , Xia Xiao , Li Guangxi
Published: December 2022

Background:

Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder. Despite our enormous progress in the strategies used to diagnose, treat, and cure WAS, no bibliometric studies have been performed in this research field. This study explored the trends in WAS research through a bibliometric analysis evaluating relevant literature quantitatively and qualitatively.

Methods:

The literature concerning WAS from 2001 to 2021 was retrieved from the Science Citation Index Expanded (SCI-expanded) of the Web of Science Core Collection database. Acquired data were then visually analyzed using CiteSpace and VOSviewer.

Results:

2036 papers were included in the final analysis. The annual publication outputs reached its peak in 2013 but declined in recent years. The dominant position of the United States in WAS research was quite obvious. Harvard University (USA), University College London (UK), and Inserm (France) were the three most prolific institutions. Adrian J. Thrasher exerted significant publication impact and made the most notable contributions in the field of WAS. Blood was the most influential journal with the highest publication outputs, and nearly all the top 10 journals and co-cited journals belonged to Q1. Immune dysregulation, thrombocytopenia, syndrome protein deficiency, stem cell, mutation, and diagnosis were the keywords with the strongest citation burst.

Conclusion:

From 2001 to 2021, the United States was a global leader in the WAS research. Collaboration between countries and institutions is expected to deepen and strengthen in the future. Research hotspots included pathogenesis, clinical manifestations, diagnosis, and therapy. Our results suggest a greater understanding of the mechanistic underpinnings of immune dysfunction in WAS patients, the application of targeted therapies for individual complications, and the development of curative approaches, which will remain research hotspots in the future.
The prevalence, awareness, management and influencing factors of diabetes in middle-aged and elderly in China, evidence from the CHARLS in 2015
Authors: Zhang Yu-Ling , Wu Bin-Jiang , Chen Pei , Wen Hong-Hua
Published: December 2022

Diabetes seriously affects the health of middle-aged and elderly. What we can do is to suppress the progression and avoid complications of diabetes. The aim of this study was to evaluate the prevalence, management and influencing factors in middle-aged and elderly diabetics. The data used in our study came from the follow-up survey (2015) of China Health and Retirement Longitudinal Study. After all the questionnaire data of participants was acquired, the first screening step was conducted and the participants without blood glucose or glycosylated hemoglobin test results were excluded. In the second screening step, participants without self-reported diabetes, age <45 were excluded. After data screening, STATA 16.0 software (StataCorp, USA) was used to conduct statistical analysis. Multiple logistics regression was used to analyze the influencing factors of diabetes in middle-aged and elderly. After data screening, A total of 9738 participants were enrolled in the survey of the China Health and Retirement Longitudinal Study in 2015, including diabetes 1965 and control 7773. The prevalence of diabetes in age >60 (22.20%) was significantly higher than that in age 45 to 60 (16.60%). Age, residence, physical activity, drinking, smoking and body mass index were key influencing factors according to the results of logistics regression. 46.92% diabetics were diagnosed in hospital, 22.14% were diagnosed by community medical care. 1298 among 1965 diabetes patients had standardized medication to control blood glucose, the rate was only 66.01%. The awareness rate of diabetes was only 28.75%, and the monitoring, treatment and accepting medical advice rates were 68.32%, 66.01% and 56.99% separately. The follow-up rate of diabetes was only 14.16%. Diabetes is widely prevalent in the middle-aged and elderly with the prevalence of 16.60% in the participants with age 45 to 60. The rate of self-rated diabetics underestimated the true prevalence of diabetes. Age, residence, physical activity, drinking, smoking and body mass index are key influencing factors to diabetes. Although a national diabetes health management model has been established, the awareness of diabetes was only 28.75%. Standardized diabetes registration and regular follow up should also be strictly implemented.
Factors impacting medication adherence in a birth cohort at higher risk for Hepatitis C infection
Authors: Philip Timothy J , Crosby Kimberly M , Frank-Pearce Summer G , Wendelboe Aaron M , Solberg Marie , Weakley Jennifer , Williams Mary B
Published: December 2022

Due to the high prevalence of Hepatitis C virus (HCV) infection among individuals born between 1945 and 1965, in 2012 the Centers for Disease Control and Prevention began recommending HCV screening for this birth cohort. As adherence to HCV treatment is essential for sustained virologic response, identifying factors influencing medication adherence is important. The validated Adherence to Refills and Medications Scale (ARMS) is used to study recent medication adherence in those with chronic disease. This cross-sectional pilot study assesses factors associated with reduced adherence, indicated by higher ARMS scores, among individuals in this birth cohort. To elucidate factors associated with medication adherence, measured by the ARMS score, among a birth cohort at higher risk for HCV to guide future treatment and improve adherence. Patients born between 1945 and 1965, accessing care at an academic family medicine clinic, were recruited between April and June 2019. Demographics, prior HCV diagnosis, HCV risk factors (prior imprisonment, tattoos, and intravenous drug use), depression assessment (Patient Health Questionnaire-9), adverse childhood experiences (ACEs), and ARMS scores were collected. Mean ARMS scores were compared using t tests and analysis of variance (α = 0.05), while multiple variable models were performed using linear regression. Women comprised 58% of participants (n = 76), 52% reported depression and 37% 4 or more ACEs. The mean ARMS score was 16.3 (SD = 3.43) and 10% reported prior diagnosis of HCV. In the final multiple variable model, ARMS scores were 2.3 points higher in those with mild depression (95% CI: 0.63, 4.04), 2.0 in those with at least 4 ACEs (95% CI: 0.55, 3.49), and 1.8 in those with tattoos (95% CI: 0.30, 3.28). ACEs and food insecurity were identified as confounding variables in those with moderate to severe depression. This study found medication adherence was related to depression, ACEs, tattoos, and food insecurity among patients in this birth cohort at higher risk for HCV.
Efficacy and safety of acetyl-CoA carboxylase (ACC) inhibitors in the treatment of nonalcoholic steatohepatitis (NASH): A protocol for systematic review
Authors: Xu Liubin , Yang Huili , Xu Hongling , Yang Rong , Fen Lian , Jiang Dansheng , Xu Linyi , Xing Yufeng
Published: December 2022

Background:

The pathological mechanism of nonalcoholic steatohepatitis (NASH) is closely related to abnormal lipid regulation in hepatocytes. Patients with NASH generally have a significant increase in de novo lipogenesis, which acetyl-CoA carboxylase (ACC) catalyzes the first committed step. However, the treatment with ACC inhibitors remains controversial. Thus, our study will systematically evaluate the efficacy and safety of ACC inhibitors for the treatment of NASH.

Methods:

We plan to search PubMed, Cochrane Library, Web of Science, EMBASE, Google Scholar, ClinicalTrials.gov, China Science and Technology Journal Database, Chinese Biomedical Literature Database, Wan-fang Database and China National Knowledge Infrastructure to obtain literatures from January 2015 to January 2030 under the inclusion and exclusion criteria, and include randomized controlled trials containing intervention of ACC inhibitors for NASH. The proportion of patients with reduction in ballooning, inflammation and fibrosis will be accepted as the main outcome. RoB 2 will be used for the risk of bias, as well as Egger’s test and funnel plot for reporting bias. We will adopt Review Manager 5.4.1 for data synthesis, subgroup analysis, meta-regression analysis and sensitivity analysis, and conduct trial sequential analysis and quality of evidence evaluation using trial sequential analysis 0.9.5.10 Beta software and GRADE Profiler 3.6.1 software respectively.

Results:

This systematic review will assess the proportion of patients with reduction of ballooning, inflammation and fibrosis, changes in hepatic steatosis, levels of liver enzymes and liver injury markers, metabolic parameters, safety and tolerability to measure the clinical benefits of ACC inhibitors for NASH.

Conclusion:

The conclusion of this systematic review will achieve convincing evidence to evaluate the efficacy and safety of ACC inhibitors for NASH.
Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
Authors: Gürbüz Mustafa , Kiliçkap Saadettin , Bilici Ahmet , Karadurmuş Nuri , Sezer Ahmet , Şendur Mehmet Ali Nahit , Paydaş Semra , Artaç Mehmet , Fulden Yumuk Perran , Gürsoy Pinar , Uysal Mükremin , Şenol Coşkun Hasan , Tatli Ali Murat , Selçukbiricik Fatih , Dişel Umut , Köksoy Elif Berna , Güven Deniz Can , Uğrakli Muzaffer , Akkuş Erman , Yücel Şebnem , Erol Cihan , Karakaya Serdar , Şakalar Teoman , Khanmammadov Nijat , Paksoy Nail , Demirkazik Ahmet
Published: December 2022

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients’ demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26–78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8–10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7–23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6–6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7–21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9–35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2–16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8–39.3] vs 16.5 months [95% CI: 9.3–23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.
Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn’s disease: A multicenter retrospective study
Authors: Kawano Seiji , Oka Shiro , Shiotani Akiko , Hashimoto Shinichi , Takahashi Sakuma , Handa Osamu , Takami Taro , Inaba Tomoki , Okada Hiroyuki , Tanaka Shinji
Published: December 2022

Crohn’s disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (≤20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (≤20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients.
Antibody response durability following three-dose coronavirus disease 2019 vaccination in people with HIV receiving suppressive antiretroviral therapy
Authors: Lapointe Hope R. , Mwimanzi Francis , Cheung Peter K. , Sang Yurou , Yaseen Fatima , Speckmaier Sarah , Barad Evan , Moran-Garcia Nadia , Datwani Sneha , Duncan Maggie C. , Kalikawe Rebecca , Ennis Siobhan , Young Landon , Ganase Bruce , Omondi F. Harrison , Umviligihozo Gisele , Dong Winnie , Toy Junine , Sereda Paul , Burns Laura , Costiniuk Cecilia T. , Cooper Curtis , Anis Aslam H. , Leung Victor , Holmes Daniel , DeMarco Mari L. , Simons Janet , Hedgcock Malcolm , Prystajecky Natalie , Lowe Christopher F. , Romney Marc G. , Barrios Rolando , Guillemi Silvia , Brumme Chanson J. , Montaner Julio S.G. , Hull Mark , Harris Marianne , Niikura Masahiro , Brockman Mark A. , Brumme Zabrina L.
Published: December 2022

Background:

Limited data exist regarding longer term antibody responses following three-dose coronavirus disease 2019 (COVID-19) vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-specific, Omicron BA.1-specific and Omicron BA.5-specific responses up to 6 months post-third dose in 64 PWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time.

Design:

Longitudinal observational cohort.

Methods:

We quantified wild-type-specific and Omicron-specific anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at 1, 3 and 6 months post-third vaccine dose.

Results:

Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than wild-type-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PWH and controls post-third dose (median wild-type-specific and BA.1-specific half-lives were between 66 and 74 days for both groups). Antibody function also declined significantly yet comparably between groups: 6 months post-third dose, BA.1-specific neutralization was undetectable in more than 80% of COVID-19 naive PWH and more than 90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough.

Conclusion:

Following three-dose COVID-19 vaccination, antibody response durability in PWH receiving ART is comparable with controls. PWH also mounted strong responses to breakthrough infection. Due to temporal response declines, however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third.
Osteoid Osteoma Mimicking Arthritis
Authors: Corrêa Diogo Goulart , Costa Flavia Martins
Published: December 2022

Intra-articular osteoid osteoma may simulate arthritis, due to the intra-articular presence of prostaglandin, which leads to synovitis, joint effusion, pain, and high local temperature. Also, intra-articular osteoid osteoma may present with minimum or no cortical thickening. Therefore, a high suspicion is needed for a correct and early diagnosis. Perfusion weighted imaging, such as dynamic contrast-enhanced imaging, can aid in the localization of the tumor nidus, seen as an early arterial-phase focal enhancement after the gadolinium injection, with fast washout, as a result of its hypervascularity.
COVID-19 Elective Surgery Shutdown and Operative Experience for Graduating Plastic Surgery Independent Residents
Authors: Loughran Atlee , McMackin Katherine , Tolaymat Besher , Jarrett Nicole
Published: December 2022

Introduction

The initial wave of the COVID-19 pandemic led to a temporary shutdown of elective procedures. The purpose of this study is to evaluate how the elective surgery shutdown impacted case log numbers for graduating plastic surgery independent residents.

Methods

The Accreditation Council of Graduate Medical Education graduate self-reported case logs were retrospectively compiled for graduating independent track plastic surgery residents for the year before the pandemic (2019), 4 months into the pandemic (2020) and 16 months into the pandemic (2021). Procedures were grouped into resident review committee area and totals for each area were used for analysis. Average number of cases and standard deviations were compiled. Percent change was calculated comparing each year to the prepandemic baseline. Statistical significance was determined with Studentttests comparing average number of cases. Coefficients of variation were calculated to assess for changes in interprogram variation. Average case numbers were then compared with minimum case requirements necessary for graduation.

Results

The Accreditation Council of Graduate Medical Education graduation case log statistics were available for 238 independent residents. There were no statistically significant differences in average case number for graduating independent residents for total reconstructive breast, trunk, hand and upper extremity, or total reconstructive procedures between graduation years. The average case number of total lower extremity reconstruction increased from 2019 to 2020 (average = 83–97.4,P= 0.02). The average total number of breast aesthetic cases increased between all years (average = 92, 98, 114), with the average increase from 2019 to 2021 being statistically significant (P= 0.02). Differences in head and neck aesthetic deformities and trunk and extremity deformities between years were not statistically significant. The average case number for all graduating plastic surgery independent residents exceeded the minimum case log requirements.

Conclusions

The temporary hold on elective procedures during the pandemic decreased the opportunity for plastic surgery trainees to meet minimum case log requirements. Case log data for graduating plastic surgery independent residents demonstrate that despite the temporary suspension, the pandemic did not greatly impact the average resident case numbers.
MONOCYTIC MYELOID-DERIVED SUPPRESSOR CELL EXPANSION AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS INDUCES LYMPHOCYTE DYSFUNCTION
Authors: Lesouhaitier Mathieu , Uhel Fabrice , Gregoire Murielle , Gacouin Arnaud , Frerou Aurélien , Gaudriot Baptiste , Bendavid Claude , Boukthir Sarrah , Le Tulzo Yves , Verhoye Jean-Philippe , Flecher Erwan , Roussel Mikael , Tarte Karin , Tadié Jean-Marc
Published: December 2022

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an immune paresis that predisposes to the development of postoperative infections and sepsis. Among factors responsible for CPB-induced immunosuppression, circulating myeloid-derived suppressor cells (MDSCs) have been found to induce early lymphocyte apoptosis and lymphocyte proliferation inhibition. However, the mechanisms involved are not fully understood. In this study, we found that the main lymphocyte subsets decreased significantly 24 h after cardiac surgery with CBP. As expected, cardiac surgery with CPB induced a monocytic MDSC expansion associated with an increased T-cell apoptosis and decreased proliferation capacity. Noteworthy, granulocytic MDSCs remain stable. Myeloid-derived suppressor cell depletion restored the ability of T-cell to proliferate ex vivo. After CPB, indoleamine 2,3-dioxygenase activity and IL-10 plasma level were increased such as programmed death-ligand 1 monocytic expression, whereas plasma level of arginine significantly decreased. Neither the inhibition of indoleamine 2,3-dioxygenase activity nor the use of anti–programmed death-ligand 1 or anti–IL-10 blocking antibody restored the ability of T-cell to proliferate ex vivo. Only arginine supplementation restored partially the ability of T-cell to proliferate.
Risk of Retention After OnabotulinumtoxinA Injection for Overactive Bladder in a Diverse Urban Population With High BMI and Comorbidity Rates
Authors: Aalami Harandi Arshia , Nauheim Jennifer , Abraham Nitya E.
Published: December 2022

Importance

OnabotulinumtoxinA (BTX-A) injection is a third-line therapy for overactive bladder (OAB). Patients undergoing treatment have a 6.5% chance of requiring clean intermittent catheterization (CIC) due to postoperative urinary retention (POUR).

Objective

The aim of this study was to evaluate risk factors for retention after BTX-A injections for OAB to decrease treatment hesitancy and enhance shared decision-making.

Study Design

This is a retrospective review of patients who underwent BTX-A injection for OAB at an urban university hospital between November 2015 and January 2021. Patients with neurogenic OAB, incomplete follow-up, or concomitant vaginal surgery were excluded. The primary outcome was POUR requiring CIC or postvoid residual volume (PVR) >200 mL at follow-up visit. Secondary outcomes included number of BTX-A injections, interval to reinjection, and whether patients reported symptom improvement.

Results

Our sample (N = 185) was 84% female with high prevalence of obesity (50%) and diabetes (32%). Twenty-one (11.4%) met the criteria for POUR with 17 (9.2%) requiring CIC. The retention and nonretention groups were similar in age, sex, smoking history, body mass index (BMI), hemogloblin A1c, and birth history, but significantly differed in preoperative PVR. Logistic regression revealed that patients with preoperative PVR 100+ mL had nearly 4-fold higher odds of POUR compared with patients with PVR less than 50 mL (odds ratio, 3.77; 95% confidence interval, 1.08–16.19).

Conclusions

Our findings reassure patients with high BMI, as well as their physicians, that retention after BTX-A injection is not associated with BMI. However, patients presenting with high baseline PVR (100 + mL) should be counseled regarding a potentially higher risk of retention after BTX-A injection.
Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial
Authors: Newman Diane K. , Thomas Elizabeth , Greene Heather , Haag-Molkenteller Cornelia , Varano Susann
Published: December 2022

Importance

The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer β3-adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI).

Objective

This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women.

Study Design

In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and urgency episodes. Safety was assessed through adverse events (AEs).

Results

Of the patients included in the analysis, 1286 (84.9%) were women (vibegron, n = 463; placebo, n = 459; tolterodine, n = 364). At week 12, women receiving vibegron showed significant reductions (95% confidence intervals of least squares mean differences does not include 0) from baseline versus placebo in mean daily micturitions, UUI episodes, and urgency episodes, with least squares mean differences (95% confidence intervals) of −0.5 (−0.8 to −0.2), −0.7 (−1.0 to −0.4), and −0.8 (−1.3 to −0.4), respectively. Treatment-emergent AE incidence was similar with vibegron (39%) and placebo (35%); the most common AE with incidence higher with vibegron (4.3%) than placebo (2.6%) was headache.

Conclusions

In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population.
Evidence-Informed, Interdisciplinary, Multidimensional Action Plan to Advance Overactive Bladder Research and Treatment Initiatives: Directives From State-of-the-Science Conference on Overactive Bladder and Cognitive Impairment
Authors: Sanses Tatiana V.D. , Zillioux Jacqueline , High Rachel A. , Dengler Katherine L. , Ackenbom Mary F. , DuBeau Catherine E. , Alperin Marianna , Wagg Adrian , Birder Lori A. , Dumoulin Chantale , Bavendam Tamara
Published: December 2022

This article outlines an evidence-informed, interdisciplinary, multidimensional, comprehensive action plan for the American Urogynecologic Society to improve care of women with overactive bladder (OAB) while minimizing treatment-related adverse events, including cognitive impairment. It is a “call to action” to advance basic, translational, and clinical research and summarizes initiatives developed at the State-of-the-Science Conference on OAB and Cognitive Impairment to (1) develop framework for a new OAB treatment approach in women, (2) define research gaps and future research priorities, (3) champion health equity and diversity considerations in OAB treatment, (4) foster community and promote education to remove stigma surrounding OAB and urinary incontinence, and (5) elevate visibility and impact of OAB, by creating partnerships through education and engagement with health care professionals, industry, private and public payers, funding agencies, and policymakers.
A Low-Diet Diversity Score Is Associated With Increased Risk of Growth Failure Among Children
Authors: Amirkhizi Farshad , Dibaseresht Fatemeh , Hamedi-Shahraki Soudabeh
Published: December 2022

This cross-sectional study assessed the association between dietary diversity score and risk of growth failure among 605 Iranian children aged 7 to 12 years. Dietary intake was evaluated by a validated semiquantitative food frequency questionnaire and dietary diversity score was calculated for each participant. Weight and height of children were measured and anthropometric indices including underweight, stunting, and thinness were assessed. The probability of having underweight (P for trend = .001) and stunting (P for trend <.0001) reduced with enhancing quartile of dietary diversity score. The highly varied diets may be useful in preventing growth failure in children.
The facilitators and barriers to improving functional activity and wellbeing in people with dementia: A qualitative study from the Process Evaluation of Promoting Activity, Independence and Stability in Early Dementia
Authors: Di Lorito Claudio , van der Wardt Veronika , Pollock Kristian , Howe Louise , Booth Vicky , Logan Pip , Gladman John , Masud Tahir , das Nair Roshan , Goldberg Sarah , Vedhara Kavita , O’Brien Rebecca , Adams Emma , Cowley Alison , Bosco Alessandro , Hancox Jennie , Burgon Clare , Bajwa Rupinder , Lock Juliette , Long Annabelle , Godfrey Maureen , Dunlop Marianne , Harwood Rowan H.
Published: December 2022

Background

The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial (RCT) showed no measurable benefits in activities of daily living, physical activity or quality of life.

Objective

To explore participants’ responses to PrAISED and explain the mechanisms behind a complex intervention that did not lead to expected health gains.

Methods

A process evaluation using qualitative methods, comprising interviews and researcher notes

Setting

Data were collected in participants’ homes or remotely by telephone or videoconferencing.

Sample

Eighty-eight interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. Sixty-nine interviews were conducted with 26 therapists.

Results

Participants valued the intervention as proactively addressing health issues that were of concern to them, and as sources of social contact, interaction, information, and advice. Facilitators to achieving positive outcomes included perceiving progress toward desired goals, positive expectations, therapists’ skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carryover between sessions; chronic physical health problems and intercurrent acute illness and injury; ‘tapering’ (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic.

Conclusions

Interventions aiming to maintain activity, independence and stability may not be appropriate in the context of dementia even in the mild stages of the condition. Various factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors, and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame ‘health gain’ and trial outcomes.
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19
Authors: Geyer Chiara E. , Chen Hung-Jen , Bye Alexander P. , Manz Xue D. , Guerra Denise , Caniels Tom G. , Bijl Tom P.L. , Griffith Guillermo R. , Hoepel Willianne , de Taeye Steven W. , Veth Jennifer , Vlaar Alexander P.J. ,   Amsterdam UMC COVID-19 Biobank, Vidarsson Gestur , Bogaard Harm Jan , Aman Jurjan , Gibbins Jonathan M. , van Gils Marit J. , de Winther Menno P.J. , Dunnen Jeroen den
Published: December 2022

Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyper-inflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fcγ receptor hyper-activation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive inflammation while simultaneously minimizing inhibition of antiviral immunity. We here developed anin vitroactivation assay to screen for small molecule drugs that specifically counteract antibody-induced pathology. We identified that anti-spike induced inflammation is specifically blocked by small molecule inhibitors against SYK and PI3K. We identified SYK inhibitor entospletinib as the most promising candidate drug, which also counteracted anti-spike-induced endothelial dysfunction and thrombus formation. Moreover, entospletinib blocked inflammation by different SARS-CoV-2 variants of concern. Combined, these data identify entospletinib as a promising treatment for severe COVID-19.

Graphical abstract
Socio-demographic determinants of monkeypox virus preventive behavior: a cross-sectional study in Pakistan
Authors: Jamil Hashaam , Idrees Muhammad , Idrees Kashmala , Tariq Waleed , Sayyeda Qudsia , Asghar Muhammad Sohaib , Tahir Muhammad Junaid , Akram Samra , Ullah Kaleem , Ahmed Ali , Mohanty Aroop , Padhi Bijaya Kumar , Sah Ranjit
Published: December 2022

Background

Monkeypox, a re-emerging zoonotic infectious disease, is striking the world with serious public health concerns, especially in non-endemic countries. The public’s knowledge and attitude toward the monkeypox virus (MPXV) influence their adherence to preventive strategies. Therefore, we aimed to assess the general public’s knowledge, attitudes, and perceptions (KAP) of MPXV in Pakistan.

Methods

We collected data for this cross-sectional study from 1040 participants via an online self-reported questionnaire from 5thJuly 2022 to 1stAugust 2022. The questionnaire consisted of a total of 29 items in four sections, assessing socio-demographics, knowledge, attitudes, and practices regarding MPXV. The data was analyzed using IBM SPSS V.25, and factors associated with MPXV knowledge, attitude, and practices were identified by using logistic regression analyses

Results

A total of1040participants were included. 61.4% were male and 57.2% had graduation level education. Only 34.4% had good knowledge about MPXV and 30% were aware of effectiveness of smallpox vaccine against MPXV. 41.7% had positive attitude with 48.6% agreed that it is a fatal disease and 44.6% were in favor of banning travelling from endemic to non-endemic regions.57.7% had good practices and 69.9% would use protective measures if MPXV become an epidemic. Binary logistic regression analysis revealed that gender and education significantly impacted knowledge (p<0.05). While monthly income status had a significant impact on attitudes (p<0.05). The practices were correlated positively with gender and education (p<0.05).

Conclusion

The majority of study participants had inadequate levels of knowledge, and attitudes regarding MPXV. To prevent the emergence and spread of MPXV in Pakistan, a comprehensive strategic framework for public health education must be established and implemented.
Inhibition of the DENV2 and ZIKV RNA polymerases by Galidesivir triphosphate measured using a continuous fluorescence assay
Authors: Deshpande Sandesh , Huo Wenjuan , Shrestha Rinu , Sparrow Kevin , Evans Gary B. , Harris Lawrence D. , Kingston Richard L. , Bulloch Esther M. M.
Published: December 2022

Millions of people are infected by the Dengue and Zika viruses each year, which can result in serious illness, permanent disability or death. There are currently no FDA-approved antivirals for treating infection by these viruses. Galidesivir is an adenosine nucleoside analog which can attenuate flavivirus replication in cell-based and animal models of infection. Galidesivir is converted to the triphosphorylated form by host kinases, and subsequently incorporated into viral RNA by viral RNA-dependent RNA polymerases, leading to the termination of RNA synthesis via an unknown mechanism. Here we report the directin vitrotesting of the effects of Galidesivir triphosphate on RNA synthesis by the polymerases of Dengue-2 and Zika virus. Galidesivir triphosphate was chemically synthesized and inhibition of RNA synthesis followed using a continuous fluorescence-based assay. Galidesivir triphosphate was equipotent against the polymerase activity of Dengue-2 and Zika, with IC50values of 42 ± 12 μM and 47 ± 5 μM, respectively. This modest potencyin vitrois consistent with results previously obtained in cell-based antiviral assays and suggests that the binding affinity for Galidesivir triphosphate is similar to the natural ATP substrate that it closely mimics. The inhibition assay we have developed will allow the rapid screening of Galidesivir and related compounds against other flavivirus polymerases, and the availability of Galidesivir triphosphate will allow detailed analysis of its mechanism of action.

Highlights

Galidesivir triphosphate was chemically synthesized.

A continuous assay detecting double-stranded RNA formation was optimized for polymerase inhibition studies.

Galidesivir triphosphate has moderate potency against DENV2 and ZIKA polymerase activity.

The availability of Galidesivir triphosphate will facilitate study of its mechanism of action.
Wastewater monitoring of SARS-CoV-2 RNA at K-12 schools: Comparison to pooled clinical testing data
Authors: Kim Sooyeol , Boehm Alexandria B.
Published: December 2022

Background

Wastewater measurements of SARS-CoV-2 RNA have been extensively used to supplement clinical data on COVID-19. Most examples in the literature that describe wastewater monitoring for SARS-CoV-2 RNA use samples from wastewater treatment plants and individual buildings that serve as the primary residence of community members. However, wastewater surveillance can be an attractive supplement to clinical testing in K-12 schools where individuals only spend a portion of their time but interact with others in close proximity, increasing risk of potential transmission of disease.

Methods

Wastewater samples were collected from two K-12 schools in California and divided into solid and liquid fractions to be processed for detection of SARS-CoV-2. The resulting detection rate in each wastewater fraction was compared to each other and the detection rate in pooled clinical specimens.

Results

Most wastewater samples were positive for SARS-CoV-2 RNA when clinical testing was positive (75% for solid samples and 100% for liquid samples). Wastewater samples continued to test positive for SARS-CoV-2 RNA when clinical testing was negative or in absence of clinical testing (83% for both solid and liquid samples), indicating presence of infected individuals in the schools. Wastewater solids had a higher concentration of SARS-CoV-2 than wastewater liquids on an equivalent mass basis by three orders of magnitude.
Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals
Authors: Justs Karlis A. , Sempertegui Sergio , Riboul Danielle V. , Oliva Carlos D. , Durbin Ryan J. , Crill Sarah , Su Chenchen , Renden Robert B. , Fily Yaouen , Macleod Gregory T.
Published: December 2022

Neural function relies on cellular energy supplies meeting the episodic demands of synaptic activity, but little is known about the extent to which power demands (energy demands per unit time) fluctuate, or the mechanisms that match supply with demand. Here, in individually-identified glutamatergic motor neuron terminals ofDrosophilalarvae, we leveraged prior macroscopic estimates of energy demand to generate profiles of power demand from one action potential to the next. These profiles show that signaling demands can exceed non-signaling demands 10-fold within milliseconds, and terminals with the greatest fluctuation (volatility) in power demand have the greatest mitochondrial volume and packing density. We elaborated on this quantitative approach to simulate adenosine triphosphate (ATP) levels during activity and drove ATP production as a function of the reciprocal of the energy state, but this canonical feedback mechanism appeared to be unable to prevent ATP depletion during locomotion. Muscle cells possess a phosphagen system to buffer ATP levels but phosphagen systems have not been described for motor nerve terminals. We examined these terminals for evidence of a phosphagen system and found the mitochondria to be heavily decorated with an arginine kinase, the key element of invertebrate phosphagen systems. Similarly, an examination of mouse cholinergic motor nerve terminals found mitochondrial creatine kinases, the vertebrate analogues of arginine kinases. Knock down of arginine kinase inDrosophilaresulted in rapid depletion of presynaptic ATP during activity, indicating that, in motor nerve terminals, as in muscle, phosphagen systems play a critical role in matching power supply with demand.

SIGNIFICANCE

Failure of metabolic processes to supply neurons with energy at an adequate rate can lead to synaptic dysfunction and cell death under pathological conditions. Using a quantitative approach at fruit fly motor nerve terminals we generated the first temporal profiles of presynaptic power demand during locomotor activity. This approach revealed challenges for the known mechanisms that match cellular power supply to demand. However, we discovered that motor nerve terminals in fruit flies and mice alike are supported by phosphagen systems, more commonly seen in muscles where they store energy and buffer mismatch between power supply and demand. This study highlights an understudied aspect of neuronal bioenergetics which may represent a bulwark against the progression of some neuropathologies.
Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity
Authors: Balouek Julie-Anne , Mclain Christabel , Minerva Adelaide R. , Rashford Rebekah L. , Bennett Shannon N. , Peña Catherine Jensen
Published: December 2022

Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser-extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles.
Tobacco smoke exposure results in recruitment of inflammatory airspace monocytes and accelerated growth ofMycobacterium tuberculosis
Authors: Corleis Bjӧrn , Tzouanas Constantine N. , Wadsworth Marc H , Cho Josalyn L , Linder Alice H , Schiff Abigail E , Dickey Amy K , Medoff Benjamin D , Shalek Alex K. , Kwon Douglas S
Published: December 2022

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive toMycobacterium tuberculosis(Mtb) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current- and never-smokers by performing single-cell RNA-sequencing (scRNA-seq), flow cytometry, and functional assays. We observed enrichment of immature inflammatory monocytes in the lungs of smokers compared to non-smokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease (COPD). Using integrative scRNA-seq and flow cytometry, we identify CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provide evidence that recruitment of monocytes into the lung is mediated by CCL11 binding to CCR2. We also show that these cells exhibit elevated inflammatory responses upon exposure toMtband accelerated intracellular growth ofMtbcompared to mature macrophages. This elevatedMtbgrowth could be inhibited with an anti-inflammatory small molecule, providing a direct connection between smoking-induced pro-inflammatory states and permissiveness toMtbgrowth. Our findings suggest a model in which smoking leads to recruitment of immature inflammatory monocytes from the periphery to the lung via CCL11-CCR2 interactions, which results in the accumulation of theseMtbpermissive cells in the airway. This work defines how smoking may lead to increased susceptibility toMtband identifies novel host-directed therapies to reduce the burden of TB among those who smoke.

One Sentence Summary

Inflammatory monocytes are recruited to the airways of smokers where they may contribute to more rapid growth ofMycobacterium tuberculosisin the lungs.
Connectome-based predictive modeling shows sex differences in brain-based predictors of memory performance
Authors: Ju Suyeon , Horien Corey , Shen Xilin , Abuwarda Hamid , Trainer Anne , Constable R Todd , Fredericks Carolyn A.
Published: December 2022

Alzheimer’s disease (AD) takes a more aggressive course in women than men, with higher prevalence and faster progression. Amnestic AD specifically targets the default mode network (DMN), which subserves short-term memory; past research shows relative hyperconnectivity in the posterior DMN in aging women. Higher reliance on this network during memory tasks may contribute to women’s elevated AD risk. Here, we applied connectome-based predictive modeling (CPM), a robust linear machine-learning approach, to the Lifespan Human Connectome Project-Aging (HCP-A) dataset (n=579). We sought to characterize sex-based predictors of memory performance in aging, with particular attention to the DMN. Models were evaluated using cross-validation both across the whole group and for each sex separately. Whole-group models predicted short-term memory performance with accuracies ranging from ρ=0.21-0.45. The best-performing models were derived from an associative memory task-based scan. Sex-specific models revealed significant differences in connectome-based predictors for men and women. DMN activity contributed more to predicted memory scores in women, while within- and between-visual network activity contributed more to predicted memory scores in men. While men showed more segregation of visual networks, women showed more segregation of the DMN. We demonstrate that women and men recruit different circuitry when performing memory tasks, with women relying more on intra-DMN activity and men relying more on visual circuitry. These findings are consistent with the hypothesis that women draw more heavily upon the DMN for recollective memory, potentially contributing to women’s elevated risk of AD.