bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between gender-based violence and poor treatment outcomes among transgender women living with HIV in Brazil
Authors: de Sousa Mascena Veras Maria Amelia , Menezes Neia Prata , Mocello Adrienne Rain , Leddy Anna M. , Saggese Gustavo Santa Roza , Bassichetto Katia Cristina , Gilmore Hailey J , de Carvalho Paula Galdino Cardin , Maschião Luca Fasciolo , Neilands Torsten B. , Sevelius Jae , Lippman Sheri A.
Published: March 2024

Background

Transgender women are disproportionately affected by both HIV and gender-based violence (GBV), defined as physical, sexual, or emotional violence perpetrated against an individual based on their gender identity/expression. While a growing body of evidence demonstrates that GBV leads to poor HIV care and treatment outcomes among cisgender women, less research has examined this association among transgender women. We assessed the impact of lifetime experiences of GBV on subsequent retention in HIV care and laboratory confirmed viral suppression among a sample of transgender women living with HIV (TWH) in Brazil.

Methods

A pilot trial of a peer navigation intervention to improve HIV care and treatment among TWH was conducted in São Paulo, Brazil between 2018 and 2019. TWH were recruited and randomized into the intervention or control arm and participated in a baseline and 9-month follow-up survey and ongoing extraction of clinical visit, prescribing, and laboratory data. Generalized linear model regressions with a Poisson distribution estimated the relative risk (RR) for the association of lifetime physical and sexual violence reported at baseline with treatment outcomes (retention in HIV care and viral suppression) at follow-up, adjusting for baseline sociodemographic characteristics.

Results

A total of 113 TWH participated in the study. At baseline, median age was 30 years, and the prevalence of lifetime physical and sexual violence was 62% and 45%, respectively. At follow-up, 58% (n = 66/113) were retained in care and 35% (n = 40/113) had evidence of viral suppression. In adjusted models, lifetime physical violence was non-significantly associated with a 10% reduction in retention in care (aRR: 0.90, 95% CI: 0.67, 1.22) and a 31% reduction in viral suppression (aRR: 0.69; 95% CI: 0.43, 1.11). Lifetime sexual violence was non-significantly associated with a 28% reduction in retention in HIV care (aRR: 0.72, 95% CI: 0.52, 1.00) and significantly associated with a 56% reduction in viral suppression (aRR: 0.44; 95% CI: 0.24, 0.79).

Conclusion

Our findings are among the first to demonstrate that lifetime experiences with physical and sexual violence are associated with poor HIV outcomes over time among transgender women. Interventions seeking to improve HIV treatment outcomes should assess and address experiences of GBV among this population.

Trial registration

ClinicalTrials.gov Identifier: NCT03525340.
Trends of alcohol-attributable deaths in Lithuania 2001–2021: epidemiology and policy conclusions
Authors: Rehm Jürgen , Rovira Pol , Jiang Huan , Lange Shannon , Shield Kevin D. , Tran Alexander , Štelemėkas Mindaugas
Published: March 2024

Background

Lithuania, a Baltic country in the European Union, can be characterized by high alcohol consumption and attributable burden. The aim of this contribution is to estimate the mortality burden due to alcohol use for the past two decades based on different relative risk functions, identify trends, and analyse the associations of alcohol-attributable burden with alcohol control policies and life expectancy.

Methods

The standard methodology used by the World Health Organization for estimating alcohol-attributable mortality was employed to generate mortality rates for alcohol-attributable mortality, standardized for Lithuania’s 2021 population distribution. Joinpoint analysis, T-tests, correlations, and regression analyses including meta-regressions were used to describe trends and associations.

Results

Age-standardized alcohol-attributable mortality was high in Lithuania during the two decades between 2001 and 2021, irrespective of which relative risks were used for the estimates. Overall, there was a downward trend, mainly in males, which was associated with four years of intensive implementation of alcohol control policies in 2008, 2009, 2017, and 2018. For the remaining years, the rates of alcohol-attributable mortality were stagnant. Among males, the correlations between alcohol-attributable mortality and life expectancy were 0.90 and 0.76 for Russian and global relative risks respectively, and regression analyses indicated a significant association between changes in alcohol-attributable mortality and life expectancy, after controlling for gross domestic product.

Conclusions

Male mortality and life expectancy in Lithuania were closely linked to alcohol-attributable mortality and markedly associated with strong alcohol control policies. Further implementation of such policies is predicted to lead to further improvements in life expectancy.
The efficacy of extracellular vesicles for acute lung injury in preclinical animal models: a meta-analysis
Authors: Zhang Xuefeng , Cheng Zongyong , Zeng Menghao , He Zhihui
Published: March 2024

Background

With the increasing research on extracellular vesicles (EVs), EVs have received widespread attention as biodiagnostic markers and therapeutic agents for a variety of diseases. Stem cell-derived EVs have also been recognized as a new viable therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). To assess their efficacy, we conducted a meta-analysis of existing preclinical experimental animal models of EVs for ALI treatment.

Methods

The database was systematically interrogated for pertinent data encompassing the period from January 2010 to April 2022 concerning interventions involving extracellular vesicles (EVs) in animal models of acute lung injury (ALI). The lung injury score was selected as the primary outcome measure for statistical analysis. Meta-analyses were executed utilizing RevMan 5.3 and State15.1 software tools.

Results

The meta-analyses comprised 31 studies, exclusively involving animal models of acute lung injury (ALI), categorized into two cohorts based on the presence or absence of extracellular vesicle (EV) intervention. The statistical outcomes from these two study groups revealed a significant reduction in lung injury scores with the administration of stem and progenitor cell-derived EVs (SMD = -3.63, 95% CI [-4.97, -2.30],P < 0.05). Conversely, non-stem cell-derived EVs were associated with an elevation in lung injury scores (SMD = -4.34, 95% CI [3.04, 5.63],P < 0.05). EVs originating from stem and progenitor cells demonstrated mitigating effects on alveolar neutrophil infiltration, white blood cell counts, total cell counts in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight ratios (W/D), and total protein in BALF. Furthermore, pro-inflammatory mediators exhibited down-regulation, while anti-inflammatory mediators demonstrated up-regulation. Conversely, non-stem cell-derived EVs exacerbated lung injury.

Conclusion

In preclinical animal models of acute lung injury (ALI), the administration of extracellular vesicles (EVs) originating from stem and progenitor cells demonstrably enhances pulmonary function. This ameliorative effect is attributed to the mitigation of pulmonary vascular permeability and the modulation of immune homeostasis, collectively impeding the progression of inflammation. In stark contrast, the utilization of EVs derived from non-stem progenitor cells exacerbates the extent of lung injury. These findings substantiate the potential utility of EVs as a novel therapeutic avenue for addressing acute lung injury.
Knockdown of the UL-16 binding protein 1 promotes osteoblast differentiation of human mesenchymal stem cells by activating the SMAD2/3 pathway
Authors: Lai Zhen , Li Mingming , Yang Xiaodong , Xian Zhenjie
Published: March 2024

Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-β signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-β signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles’ heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.
Circulating levels of asprosin in children with obesity: a systematic review and meta-analysis
Authors: Zhang Yuwei , Zhang Yifei , Yang Bao , Li Simin , Jia Ru
Published: March 2024

Background

Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children.

Methods

Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher’s Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI.

Results

Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:—0.22–0.95, p = 0.22). However, Fisher’s Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher’s Z: 0.11, 95% CI: 0.02–0.20, p = 0.02).

Conclusions

Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic.

Trial registration

Prospero ID: CRD42023426476.
Real-time evaluation and adaptation to facilitate rapid recruitment in a large, prospective cohort study
Authors: Honushefsky Ashley , Wagner Eric S. , Sheridan Kathleen , Spickard Kathleen M. , LeMasters William R. , Walter Carroll N. , Beaver Taryn , Lennon Anne Marie , Papadopoulos Nickolas , Rahm Alanna Kulchak , Buchanan Adam H.
Published: March 2024

Background

Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities. Here we discuss the implementation of various recruitment strategies for enrolling participants into a large, prospective cohort study, assessing the need for adaptations and making them in real-time, while maintaining high adherence to the protocol and high participant satisfaction.

Methods

While conducting a large, prospective trial of a multi-cancer early detection blood test at Geisinger, an integrated health system in central Pennsylvania, we monitored recruitment progress, adherence to the protocol, and participants’ satisfaction. Tracking mechanisms such as paper records, electronic health records, research databases, dashboards, and electronic files were utilized to measure each outcome. We then reviewed study procedures and timelines to list the implementation strategies that were used to address barriers to recruitment, protocol adherence and participant satisfaction.

Results

Adaptations to methods that contributed to achieving the enrollment goal included offering multiple recruitment options, adopting group consenting, improving visit convenience, increasing the use of electronic capture and the tracking of data and source documents, staffing optimization via leveraging resources external to the study team when appropriate, and integrating the disclosure of study results into routine clinical care without adding unfunded work for clinicians. We maintained high protocol adherence and positive participant experience as exhibited by a very low rate of protocol deviations and participant complaints.

Conclusion

Recruiting rapidly for large studies – and thereby facilitating clinical translation – requires a nimble, creative approach that marshals available resources and changes course according to data. Planning a rigorous assessment of a study’s implementation outcomes prior to study recruitment can further ground study adaptations and facilitate translation into practice. This can be accomplished by proactively and continuously assessing and revising implementation strategies.
Reconstructing the ancestral gene pool to uncover the origins and genetic links of Hmong–Mien speakers
Authors: Gao Yang , Zhang Xiaoxi , Chen Hao , Lu Yan , Ma Sen , Yang Yajun , Zhang Menghan , Xu Shuhua
Published: March 2024

Background

Hmong–Mien (HM) speakers are linguistically related and live primarily in China, but little is known about their ancestral origins or the evolutionary mechanism shaping their genomic diversity. In particular, the lack of whole-genome sequencing data on the Yao population has prevented a full investigation of the origins and evolutionary history of HM speakers. As such, their origins are debatable.

Results

Here, we made a deep sequencing effort of 80 Yao genomes, and our analysis together with 28 East Asian populations and 968 ancient Asian genomes suggested that there is a strong genetic basis for the formation of the HM language family. We estimated that the most recent common ancestor dates to 5800 years ago, while the genetic divergence between the HM and Tai–Kadai speakers was estimated to be 8200 years ago. We proposed that HM speakers originated from the Yangtze River Basin and spread with agricultural civilization. We identified highly differentiated variants between HM and Han Chinese, in particular, a deafness-related missense variant (rs72474224) in theGJB2gene is in a higher frequency in HM speakers than in others.

Conclusions

Our results indicated complex gene flow and medically relevant variants involved in the HM speakers’ evolution history.
The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study
Authors: Solbakken Siri Marie , Meyer Haakon Eduard , Dahl Cecilie , Finnes Trine Elisabeth , Hjellvik Vidar , Nielsen Christopher Sivert , Omsland Tone Kristin , Stigum Hein , Holvik Kristin
Published: March 2024

Background

Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture.

Methods

Individual-level data on medications dispensed from pharmacies (2005–2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006–2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model.

Results

During 2006–2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1–5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21–25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51–65 years.

Conclusions

Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.
Invitro antibacterial activity of bark, leaf and root extracts of combretum molle plant against streptococcus equi isolated from clinical cases of strangles in donkeys and horses
Authors: Emiru Ayechew Yetayeh , Regassa Fekadu , Endebu Duguma Bojia , Kassaye Asmamaw , Desyebelew Belay
Published: March 2024

Background

Effective therapy for many infections is becoming difficult due to the evolutionary development of drug resistance, and hence, the development of alternative treatment options mainly from herbs is crucial. The objective of this study was to investigate the antibacterial effects of ethanol extracts of stem bark, leaves and roots of Combretum molle against Streptococcus equi isolated from clinical cases of strangles using in vitro tests.

Methods

Plant extraction was performed using a maceration technique with 80% ethanol. The mean zone of inhibition was determined using the agar well diffusion method. Six serial dilutions with different concentrations (10%, 5%, 2.5%, 1.25%, 0.625% and 0.3125%) of each plant extract were prepared using dimethyl sulfoxide (DMSO). A modified agar microdilution method was used to determine the minimum inhibitory concentration (MICs) of the extracts.

Results

The results revealed that all plant extracts showed significant antibacterial activity. The root extract showed the best antibacterial effect compared to the others at all concentrations, with MZI values of 27.5, 23.225, 20.5, 17.9, 15.65 and 12.25 for the respective concentrations mentioned above and an MIC of 250 µg/ml. It was followed by the stem bark extract, which had MZI values of 24.67, 22.35, 18.225, 16.175, 11.125 and 8.2 millimeters and an MIC of 375 µg/ml. The leaf extract also had significant activity, with MZI values of 20.175, 18.25, 15.7, 13.125, 9.4 and 6.75 in millimeters and an MIC of 500 µg/ml. There was a direct relationship between the concentrations of the plant extracts and the level of inhibition.

Conclusion

The test plant extracts were compared with the conventional antibiotic penicillin G, and the results indicated that the parts of the test plant have significant antibacterial activity, which may support traditional claims and could be candidates for alternative drug discoveries.
Unveiling the silver lining: examining the effects of biogenic silver nanoparticles on the growth dynamics of in vitro olive shoots
Authors: Hasanin Mohamed S. , Hassan Sayed A.M. , AbdAllatif A. M. , Darwesh Osama M.
Published: March 2024

The current study aimed to evaluate the effects of biogenic silver nanoparticles (AgNPs) on growth behavior and leaf anatomy of in vitro growing shoots of ‘Picual’ and ‘Dolce’ olive cultivars. Biosynthesis of AgNPs was carried out using the cell-free filtrate of Fusarium oxysporum. The dimension and shape of the synthesized AgNPs have been analyzed using spectroscopy and topography analysis tools, confirming that the biosynthesis of AgNPs is a crystalline nanostructure with an average particle size of 37 nm. The shoots of the selected olive cultivars were cultured on Rugini olive medium-supplemented AgNPs at 0, 10, 20, and 30mg L− 1. The effect of genotypes on shoot multiplication was significant, ‘Picual’ recorded higher values of shoot growth parameters compared with ‘Dolce’ cultivar. Adding AgNPs to the culture medium significantly affected the growth of in vitro olive shoots. AgNPs at 20 and 30mg L− 1 produced higher values of the number of shoots, shoot length, and leaf number of Picual cv. compared with the control treatments, but the higher AgNPs concentration harmed the growth parameters of Dolce cv. and recorded lower growth values compared with the lower concentration (10mg L− 1). AgNPs had a significant effect on leaf morphology and their anatomical structure. The current results showed that the stimulatory effect of AgNPs on shoot growth of in vitro olive shoots is highly dependent on plant genotype and nanoparticle concentration.
Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns
Authors: Eghtesad Sareh , Masoudi Sahar , Sharafkhah Maryam , Rashidkhani Bahram , Esmaeili-Nadimi Ali , Najafi Farid , Faramarzi Elnaz , Homayounfar Reza , Ebrahimnejad Pedram , Ansari-Moghaddam Alireza , Mirjalili Mohammadreza , Poustchi Hossein , Willett Walter C , Malekzadeh Reza , Hekmatdoost Azita
Published: March 2024

Background

Dietary patterns, encompassing an overall view of individuals’ dietary intake, are suggested as a suitable means of assessing nutrition’s role in chronic disease development. The aim of this study was to evaluate the validity and reproducibility of a food frequency questionnaire (FFQ) designed for use in the Prospective Epidemiological Research Studies in IrAN (PERSIAN), by comparing major dietary patterns assessed by the FFQ with a reference method.

Methods

Study participants included men and women who enrolled in the PERSIAN Cohort Study at seven of the eighteen centers. These centers were chosen to include dietary variations observed among the different Iranian ethnic populations. Two FFQ were completed for each participant over a one-year study period (FFQ1 upon enrollment and FFQ2 at the end of the study), with 24 interviewer-administered 24-hour dietary recalls (24 h) being completed monthly in between. Spearman correlation coefficients (SCC) were used comparing FFQs 1 and 2 to the 24 h to assess validity, while FFQ1 was compared to FFQ2 to assess reproducibility of the questionnaire.

Results

Three major dietary patterns—Healthy, Low Protein/High Carb and Unhealthy—were identified, accounting for 70% of variance in the study population. Corrected SCC ranged from 0.31 to 0.61 in the validity and from 0.34 to 0.57 in reproducibility analyses, with the first two patterns, which accounted for over 50% of population variance, correlated at above 0.5 in both parameters, showing acceptable findings.

Conclusions

The PERSIAN Cohort FFQ is suitable for identification of major dietary patterns in the populations it is used for, in order to assess diet-disease relationships.
The Wearable Activity Tracker Checklist for Healthcare (WATCH): a 12-point guide for the implementation of wearable activity trackers in healthcare
Authors: Szeto Kimberley , Arnold John , Maher Carol
Published: March 2024

Increasing physical activity in patients offers dual benefits, fostering improved patient health and recovery, while also bolstering healthcare system efficiency by minimizing costs related to extended hospital stays, complications, and readmissions. Wearable activity trackers offer valuable opportunities to enhance physical activity across various healthcare settings and among different patient groups. However, their integration into healthcare faces multiple implementation challenges related to the devices themselves, patients, clinicians, and systemic factors. This article presents the Wearable Activity Tracker Checklist for Healthcare (WATCH), which was recently developed through an international Delphi study. The WATCH provides a comprehensive framework for implementation and evaluation of wearable activity trackers in healthcare. It covers the purpose and setting for usage; patient, provider, and support personnel roles; selection of relevant metrics; device specifications; procedural steps for issuance and maintenance; data management; timelines; necessary adaptations for specific scenarios; and essential resources (such as education and training) for effective implementation. The WATCH is designed to support the implementation of wearable activity trackers across a wide range of healthcare populations and settings, and in those with varied levels of experience. The overarching goal is to support broader, sustained, and systematic use of wearable activity trackers in healthcare, therefore fostering enhanced physical activity promotion and improved patient outcomes.
Zero-leak prediction during major lung resection aiming for minimal chest drainage duration: a retrospective analysis
Authors: Sueyoshi Kuniyo , Merlini McAndrew , Otsubo Kosuke , Kojima Fumitsugu , Bando Toru
Published: March 2024

Background

Early chest tube removal should be considered to enhance recovery after surgery. The current study aimed to provide a predictive algorithm for air leak episodes (ALE) and to create a knowledge base for early chest tube removal.

Methods

This retrospective study enrolled patients who underwent thoracoscopic anatomical pulmonary resections in our unit. We defined ALE as any airflow ≥ 10 mL/min recorded in the follow-up charts based on the digital thoracic drainage device. Multivariate regression analysis was used to control for preoperative and intraoperative confounding factors. The ALE prediction algorithm was constructed by combining an additive ALE risk-scoring system using the coefficients of the significant predictive factors with the intraoperative water-sealing test.

Results

In 485 consecutive thoracoscopic major pulmonary resections, ALE developed in 209 (43%) patients. Statistically significant ALE-associated preoperative factors included male sex, lower body mass index, radiologically evident emphysema, lobectomy, and upper lobe surgery. Significant ALE-associated intraoperative factors were incomplete fissure and pleural adhesion. The ALE risk scoring demonstrated an average area under the receiver operating characteristic curve of 0.72 in the fivefold cross-validation test. The ALE prediction algorithm correctly predicted ALE-absent patients at a negative predictive value of 80%.

Conclusions

The algorithm may promote the optimization of the chest tube-dwelling duration by identifying potential ALE-absent patients for accelerated tube removal.
De novo variants of IRF2BPL result in developmental epileptic disorder
Authors: Wang Yong , Ke Zhongling , Li Yufen , Qiu Mingqi , Liu Jing , Yang Zuozhen , Wen Shu , Liang Mengmeng , Chen Shan
Published: March 2024

Background

Pathogenic variants of the IRF2BPL gene have been reported to cause neurodevelopmental disorders; however, studies focused on IRF2BPL in zebrafish are limited.

Results

We reported three probands diagnosed with developmental delay and epilepsy and investigated the role of IRF2BPL in neurodevelopmental disorders in zebrafish. The clinical and genetic characteristics of three patients with neurodevelopmental disorder with regression, abnormal movements, loss of speech and seizures (NEDAMSS) were collected. Three de novo variants (NM_024496.4: c.1171 C > T, p.Arg391Cys; c.1157 C > T, p.Thr386Met; and c.273_307del, p.Ala92Thrfs*29) were detected and classified as pathogenic or likely pathogenic according to ACMG guidelines. Zebrafish crispants with disruption of the ortholog gene irf2bpl demonstrated a reduced body length and spontaneous ictal-like and interictal-like discharges in an electrophysiology study. After their spasms were controlled, they gain some development improvements.

Conclusion

We contribute two new pathogenic variants for IRF2BPL related developmental epileptic disorder which provided evidences for genetic counseling. In zebrafish model, we for the first time confirm that disruption of irf2bpl could introduce spontaneous electrographic seizures which mimics key phenotypes in human patients. Our follow-up results suggest that timely cessation of spasmodic seizures can improve the patient’s neurodevelopment.
Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis
Authors: Wang Guangwei , Liu Xiaofei , You Yue , Chen Silei , Chang Xiaohan , Yang Qing
Published: March 2024

Objective

Tumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells.

Methods

Stem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool “ConsensusClusterPlus.” Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model’s clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes.

Results

Utilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature’s independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues.

Conclusion

The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.
Etiological analysis of 167 cases of drug-resistant epilepsy in children
Authors: Zuo Ran-Ran , Jin Mei , Sun Su-Zhen
Published: March 2024

Background

To analyze the etiological distribution characteristics of drug-resistant epilepsy (DRE) in children, with the aim of providing valuable perspectives to enhance clinical practice.

Methods

In this retrospective study, clinical data were collected on 167 children with DRE who were hospitalized between January 2020 and December 2022, including gender, age of onset, seizure types, video electroencephalogram(VEEG) recordings, neuroimaging, and genetic testing results. Based on the etiology of epilepsy, the enrolled children were categorized into different groups. The rank-sum test was conducted to compare the age of onset for different etiologies.

Results

Of the 167 cases, 89 (53.3%) had a clear etiology. Among them, structural factors account for 23.4%, genetic factors for 19.2%, multiple factors for 7.2%, and immunological factors for 3.6%. The age of onset was significantly earlier in children with genetic causes than those with structural (P < 0.001) or immunological (P = 0.001) causes.

Conclusions

More than half of children with DRE have a distinct underlying cause, predominantly attributed to structural factors, followed by genetic factors. Genetic etiology primarily manifests at an early age, especially among children aged less than one year. This underscores the need for proactive enhancements in genetic testing to unveil the underlying causes and subsequently guide treatment protocols.
Thermodynamic investigation on the aqueous mixtures of choline chloride/propylene glycol deep eutectic solvent at T = (293.15 to 313.15) K
Authors: Zarghampour Aynaz , Jafari Parisa , Rahimpour Elaheh , Jouyban Abolghasem
Published: March 2024

This work focuses on physicochemical features of the choline chloride/propylene glycol deep eutectic solvent (DES) + water mixtures by determining their density values in mono- and mixed- states over various temperatures in the range of 293.15–318.15 K. The density data obtained from measurements were utilized for the computation of various quantities such as excess molar volumes, molar volume, apparent molar volume, limiting apparent molar expansibility, and isobaric thermal expansion coefficient. Furthermore, the experimental densities were fitted to some mathematical equations such as Jouyban-Acree, Jouyban-Acreevan’t Hoff, modified Jouyban-Acree-van’t Hoff, Redlich–Kister and Emmerling. Studies of this nature can provide useful insights into solute–solvent interactions in aqueous solutions of DES, especially about to their novel application in drug solubilization.
Compliance with infection prevention and control standard precautions and factors associated with noncompliance among healthcare workers working in public hospitals in Addis Ababa, Ethiopia
Authors: Senbato Feyissa Regassa , Wolde Deneke , Belina Merga , Kotiso Kehabtimer Shiferaw , Medhin Girmay , Amogne Wondwossen , Eguale Tadesse
Published: March 2024

Background

Standard Precautions (SPs) are the minimal infection prevention and control (IPC) measures that apply to all patient care activities at all times, regardless of whether the patient has a suspected or proven disease, in any place where healthcare service is provided. These evidence-based practices protect healthcare workers (HCWs) from infection while preventing the spread of infectious agents among patients, visitors, and the environment.

Objectives

Assessed compliance of HCWs working in public hospitals in Addis Ababa to infection prevention and control SPs, and factors associated with noncompliance.

Methods

In a hospital-based cross-sectional study, 422 HCWs were recruited from nine public hospitals in Addis Ababa using a stratified random sampling technique. Data were collected using self-administered questionnaires, entered into a computer using Epi data, and analyzed using SPSS version 25. The association between the independent and the outcome variables was investigated using logistic regression. Odd ratios with corresponding 95% confidence intervals (CI) were used as measures of the strength of the association between the outcome and the explanatory variables. Ap-value below 5% was considered an indicator of statistical significance.

Results

The level of knowledge of HCWs about IPC and SPs was 51.9% and 36.49% of the respondents were compliant with SPs. Receiving IPC Training [Adjusted Odds Ratio (AOR) = 1.81, 95% CI 1.06, 3.09], knowing SPs [AOR = 3.46, 95% CI = 1.83, 6.54], presence of a mechanism in the hospital to enforce the IPC practices [AOR = 1.71 95% CI = 1.01, 2.89], and availability of cleaning and disinfection chemicals in the hospital [AOR = 2.18, 95%CI = 1.15, 4.13] were significantly associated with the HCWs’ compliance with SPs.

Conclusion

Compliance with IPC standard precautions of HCWs in public hospitals of Addis Ababa is suboptimal. Working in medical units, less work experience, lack of training, poor knowledge, absence of a mechanism to enforce adherence, and inadequate resources are independent predictors for non-compliance of the HCWs.
Effects of a 14-day social media abstinence on mental health and well-being: results from an experimental study
Authors: de Hesselle Lea C. , Montag Christian
Published: March 2024

Background and aim

The study investigated the effects of a 14-day social media abstinence on various mental health factors using an experimental design with follow-up assessment. Hypotheses included positive associations between problematic smartphone use (PSU) and depression, anxiety, fear of missing out (FoMO), and screentime. Decreases in screentime, PSU, depression and anxiety, and increases in body image were assumed for the abstinence group. Additionally, daily changes in FoMO and loneliness were explored.

Methods

Participants completed different questionnaires assessing PSU, FoMO, depression and anxiety, loneliness and body image and were randomized into control and social media abstinence groups. Daily questionnaires over 14 days assessed FoMO, loneliness, screentime, and depression and anxiety. 14 days after the abstinence, a follow-up questionnaire was administered. Multilevel models were used to assess changes over time.

Results

PSU was positively associated with symptoms of depression, anxiety and FoMO, but not with screentime. Spline models identified decreased screentime and body image dissatisfaction for the intervention group. Depression and anxiety symptoms, PSU, trait and state FoMO, and loneliness, showed a decrease during the overall intervention time but no difference between the investigated groups could be observed (hence this was an overall trend). For appearance evaluation and body area satisfaction, an increase in both groups was seen. Daily changes in both loneliness and FoMO were best modelled using cubic trends, but no group differences were significant.

Discussion

Results provide insights into effects of not using social media for 14 days and show that screentime and body image dissatisfaction decrease. The study also suggests areas for future studies to better understand how and why interventions show better results for some individuals.
Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers
Authors: Palard-Novello Xavier , Visser Denise , Tolboom Nelleke , Smith Charlotte L. C. , Zwezerijnen Gerben , van de Giessen Elsmarieke , den Hollander Marijke E. , Barkhof Frederik , Windhorst Albert D. , van Berckel Bart NM , Boellaard Ronald , Yaqub Maqsood
Published: March 2024

Background

Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.

Methods

Eight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF.

Results

For [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%).

Conclusions

For [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization.
Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study
Authors: Peterson Daniel , Van Poppel Mark , Boling Warren , Santos Perry , Schwalb Jason , Eisenberg Howard , Mehta Ashesh , Spader Heather , Botros James , Vrionis Frank D. , Ko Andrew , Adelson P. David , Lega Bradley , Konrad Peter , Calle Guillermo , Vale Fernando L. , Bucholz Richard , Richardson R. Mark
Published: March 2024

Background

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA.

Methods

The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study’s initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment.

Results

Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists.

Conclusions

The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated.

Trial registration

NCT04539964; August 31, 2020.
To evaluate the relationship of obstructive sleep apnea with chronic periodontitis and its association with coronary artery disease by assessing serum tumor necrosis factor-α
Authors: Gupta Shilpi , Lal Nand , Ali Wahid , Pradhan Akshyaya , Verma Ajay Kumar , Gupta Prashant , Kumar Neeraj , Singh Balendra Pratap , Sinha Neeraj
Published: March 2024

The periodontal tissue initiates an immune-inflammatory response against bacteria and their products at the site of periodontal infection, and systemic attack by these pathogens triggers an acute phase response that contributes to the systemic inflammatory burden. Obstructive sleep apnea (OSA) and periodontal diseases share many common risk factors and are therefore disorders associated with, and possibly related to, systemic inflammation.

Objectives 1.) To evaluate the severity of infection-causing chronic periodontitis subjects leading to Coronary Artery Disease (CAD) risk.

2.) To evaluate specific Inflammatory marker TNF-α in coronary artery disease (CAD) subjects with chronic periodontitis and obstructive sleep apnea.

Methods A total of 5 ml of the venous blood was collected from each participant which was separated out by centrifugation at 3000 rpm for 5–10 min at room temperature for the estimation of inflammatory markers. Collected samples were labeled and stored at − 20 °C in a deep freezer. The estimation of human TNF-α (tumor necrosis factor-alpha) levels was determined using an ELISA kit based on the Sandwich-ELISA principle.

Conclusion TNF-α may serve as important markers for the diagnosis of chronic periodontitis and obstructive sleep apnea and the prediction of the severity of cardiovascular diseases. Cardiovascular disease can be efficiently circumvented with a biomarker-based approach to treatment, which also benefits patients' quality of life.

Results The result of our study showed that TNF-α is involved in the onset and progression of obstructive sleep apnea leading to coronary artery disease since the expression levels of TNF in the case group were considerably higher than those in the control group.