bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Taohong Siwu decoction combined with antihypertensive medicine in the treatment of hypertension: Meta-analysis
Authors: Xie Peng-Cheng , Liang Qiu-Er , Tu Wan-Qing , Xie Ting , Lam Lai Kwan , Chen Li-Guo
Published: January 2023

Background:

Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension.

Objective:

This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension.

Methods:

According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This meta-analysis used RevMan 5.4 to evaluate the articles.

Results:

This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16–1.37,P < .00001), which could effectively reduce the systolic BP (MD = −15.28 mm Hg; 95% CI: −20.17 to −10.40,P < .00001=, diastolic BP (MD = −9.70 mm Hg; 95% CI: −12.66 to −6.73,P < .00001), Triglycerides (MD = −1.48, 95%CI: −2.09 to −0.87,P < .00001), total cholesterol (MD = −1.43, 95% CI: −1.63 to −1.24,P < .00001) and low density lipoprotein cholesterol (MD = −0.93, 95% CI: −1.07 to −0.80,P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum high-density lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46,P < .00001).

Conclusion:

THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference.
A multicenter registry of neuropsychiatric outpatients in Korean medicine hospitals (KMental): Protocol of a prospective, multicenter, registry study
Authors: Suh Hyo-Weon , Ko Youme , Moon Seunghwan , Kim Jong Woo , Chung Sun-Yong , Hong Sunggyu , Lee Hyun Woo , Huang Ching-Wen , Jang Bo-Hyoung
Published: January 2023

Introduction:

Mental health is an important global health concern. In Korea, many people visit Korean medicine clinics due to Stagnation syndrome and Hwabyung (cultural idioms of distress).

Methods and analysis:

We established a research collaboration comprising of professionals from 8 Korean medicine hospitals and planned a prospective, multicenter registry study. Demographic, socioeconomic, and clinical data will be collected from patients with mental disorders visiting the Korean medicine neuropsychiatric department of Korean medicine hospitals. We will include major psychiatric diagnoses related to neurosis and Korean traditional mental disorders such as Stagnation syndrome and Hwabyung.

We expect to identify comprehensive characteristics of participants, measure the severity of their symptoms or distress, and investigate patterns of Korean medicine interventions and treatment responses for both the short-term and long-term (at least 4 years). Additionally, this study will include Health Insurance Review & Assessment Service data to analyze the medical use of registered patients before and after registration, in case the participant submits the consent form for personal information collection and use.

To analyze the effectiveness of Korean medicine treatment for the participants, stratified or corrected analyses of age, sex, and diagnosis will be performed. The difference in the change in the psychometric measurements, quality of life measured by short form 36, and quality-adjusted life years will be calculated to evaluate the effectiveness of Korean medicine treatment.
Prevalence of internet addiction among Syrian undergraduate medical students
Authors: Latifeh Youssef , Alkhatib Yaseen , Hmidouch Mohiar , Swed Sarya , Hafez Wael , Sawaf Bisher , Rakab Amine
Published: January 2023

The purpose of this study is to determine the prevalence and risk factors for internet addiction disorder among Syrian medical students. Syrian medical students from 8 different universities participated in an online cross-sectional questionnaire study between May 13 and June 16, 2022. DASS-21 Depression, Anxiety, Stress Scale, and Internet Addiction Test were the 3 main determinants of the questionnaire. One thousand nine hundred fifty-three medical students from 8 different Syrian universities have participated in our cross-sectional. Half of the participants were from the Syrian private and Damascus universities. 62.1% were females, and most participants had good academic degrees (70–90/100). Sixty-nine percent of the study participants thought that COVID19 increased internet use rates. The Internet Addiction Scale’s average score was 33.48 ± 16.29 (1–100). The total young internet addiction test score was high among medical students from the faculty of medicine university, students from Damascus University, males, smokers, and medical students with lower academic credentials than other subgroups. Both the relationship between internet addiction and DASS-21 subgroups and the correlation between DASS-21 subgroups were statistically significant. Our research showed that internet addiction was widespread among Syrian medical students, particularly when used more for entertainment than educational purposes. Additionally, it was linked to poor academic degrees in the exams at the university and mental health conditions, including depression, anxiety, and stress.
The efficacy and safety of pre-emptive methoxamine infusion in preventing hypotension by in elderly patients receiving spinal anesthesia: A PRISMA-compliant protocol for systematic review and meta-analysis
Authors: Li Ling , He Li-Xian , Yao Yun-Tai ,   The Evidence in Cardiovascular Anesthesia (EICA) Group
Published: January 2023

Background:

Hypotension is frequent after spinal anesthesia, especially in elderly patients. Whether pre-emptive methoxamine infusion is effective and safe to prevent spinal anesthesia-induced hypotension is still a controversial issue, to dress this knowledge lack, we performed a systemic review and meta-analysis to evaluated it.

Participants:

Elderly patients undergoing spinal anesthesia.

Interventions:

Administration of methoxamine prior to spinal anesthesia.

Methods:

We searched PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and VIP Database, Chinese BioMedical Literature & Retrieval System from January 1st 1978 to February 28th 2022. Primary outcomes of interests included hemodynamic parameters, such as systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate. Secondary outcomes of interests included the incidence of intraoperative hypotension, bradycardia, nausea and vomiting, vasopressors requirement, intraoperative blood loss. For continuous or dichotomous variables, treatment effects were calculated as weighted mean difference or odds ratio, respectively.

Results:

Our search yielded 8 randomized controlled trials including 480 patients, and 240 patients were allocated into methoxamine group and 240 into control group. Meta-analysis demonstrated that pre-emptive methoxamine infusion in preventing hypotension by in elderly patients receiving spinal anesthesia had higher blood pressures, lower heart rates. Compared with the control group, the incidence of perioperative hypotension in elderly patients was lower, and elderly patients had less requirement for vasopressor in methoxamine group.

Conclusion:

This meta-analysis demonstrated that pre-emptive methoxamine infusion in elderly patients receiving spinal anesthesia can improve blood pressure, slow down heart rate, reduce the incidence of hypotension and requirement for vasopressor. However, these findings should be interpreted rigorously. Further well-conducted trials are required to confirm this.
Evaluation of STD Surveillance System Electronic Laboratory Processing in Florida: Automating Case Creation, Reporting, and Closure of Chlamydia and Gonorrhea Cases
Authors: Danforth Brandi , Matthias James , Jashinsky Jared , McCorvey Alaina
Published: January 2023

Background

Each year, Florida Department of Health staff process hundreds of thousands of electronically received laboratory results for chlamydia (CT) and gonorrhea (GC). These processing steps are currently performed manually in Florida’s surveillance system and divert from other sexually transmitted disease (STD) prevention efforts. We developed processes that would automate these procedures and evaluated the impact on potential programmatic time savings.

Methods

We evaluated 575,952 electronic CT/GC laboratory results from January 2019 through December 2021. Laboratory results were processed through the newly automated procedures and algorithms. Expected time savings were projected using conservative estimates of one minute saved every time an automated process replaced a current manual procedure: profile matching, profile creation, event record creation, case review, and case reporting. Exceptions to automatic case reporting applied to certain higher priority populations needing intervention.

Results

During this period, 297,348 electronic CT/GC laboratory results were received for people with no previous recorded history of STDs and required profile creation. In total, 386,763 new surveillance infection records were created for reporting. Of reported cases, 127,345 were from higher priority groups. The proposed automations would have saved an estimated 33,121 hours of staff time, about 11,040 hours or the work of 5.3 full time staff annually.

Conclusions

Automating current CT/GC laboratory processing would save thousands of personnel hours that could be redirected to higher priority activities. Flexibility in prioritization criteria for automated case reporting allows programs to adjust automation to disease prevention priorities and resources. Similar automation procedures could be developed by other jurisdictions or health programs.
Museum Meanderings XII
Authors: Altschuler Eric L. , Altschuler Daniel L. , Morgan Crystal N.
Published: January 2023

In the April 1930 issue of the journal, Founding Editor-in-Chief William Rush Dunton, Jr, MD, initiated a new series: Museum Meanderings. Eleven installments of the series ran intermittently until December 1931. Here, a 12th installment, an e-museum “tour” of paintings by the great American artist Jacob Lawrence (1917–2000) relevant to rehabilitation medicine, is offered. In particular, his Occupational Therapy No. 1 (1949) is a most thought-provoking and inspiring masterpiece. The painting depicts five women performing various sewing activities with space in the painting brilliantly divided. The painting has been discussed by art critics, but it has not been appreciated that all the women appear actually to be the same person! Thus, the painting shows the stages or cycle of rehabilitation. Echoing Rush Dunton’s thoughts in 1930, we invite further contributions to the series.
Interpretable Machine Learning-based Decision Support for Prediction of Antibiotic Resistance for Complicated Urinary Tract Infections
Authors: Yang Jenny , Eyre David W. , Clifton David A.
Published: January 2023

Urinary tract infections are one of the most common bacterial infections worldwide; however, increasing antimicrobial resistance in bacterial pathogens is making it challenging for clinicians to correctly prescribe patients appropriate antibiotics. In this study, we present four interpretable machine learning-based decision support systems for predicting antimicrobial resistance. Using electronic health record data from a large cohort of patients diagnosed with complicated UTIs, we demonstrate high predictability of antibiotic resistance across four antibiotics – nitrofurantoin, co-trimoxazole, ciprofloxacin, and levofloxacin. We additionally demonstrate the generalizability of our methods on a separate cohort of patients with uncomplicated UTIs. Through our study, we demonstrate that machine learning-based methods can help reduce the risk of non-susceptible treatment, facilitate rapid clinical intervention, enable more personalized approaches for treatment recommendation, while additionally allowing model interpretability that explains the basis for predictions.
Genetic architecture of brain age and its casual relations with brain and mental disorders
Authors: Leonardsen Esten H. , Vidal-Piñeiro Didac , Roe James M. , Frei Oleksandr , Shadrin Alexey A. , Iakunchykova Olena , de Lange Ann-Marie G. , Kaufmann Tobias , Taschler Bernd , Smith Stephen M. , Andreassen Ole A. , Wolfers Thomas , Westlye Lars T. , Wang Yunpeng
Published: January 2023

The difference between chronological age and the apparent age of the brain estimated from brain imaging data — the brain age gap (BAG) — is widely considered a general indicator of brain health. Converging evidence supports that BAG is sensitive to an array of genetic and non-genetic traits and diseases, yet few studies have examined the genetic architecture and its corresponding causal relationships with common brain disorders. Here, we estimate BAG using state-of-the-art neural networks trained on brain scans from 53,542 individuals (age range 3-95 years). A genome-wide association analysis across 28,104 individuals (40-84 years) from the UK Biobank revealed eight independent genomic regions significantly associated with BAG (p<5×10−8) implicating neurological, metabolic, and immunological pathways – among which seven are novel. No significant genetic correlations or causal relationships with BAG were found for Parkinson’s disease, major depressive disorder, or schizophrenia, but two-sample Mendelian randomization indicated a causal influence of AD (p=7.9×10−4) and bipolar disorder (p=1.35×10−2) on BAG. These results emphasize the polygenic architecture of brain age and provide insights into the causal relationship between selected neurological and neuropsychiatric disorders and BAG.
Effectiveness of an eHealth Intervention for Reducing Psychological Distress and Increasing COVID-19 Knowledge and Protective Behaviors among Ethnoracially Diverse Sexual and Gender Minority Adults: A Quasi-experimental Study (#SafeHandsSafeHearts)
Authors: Newman Peter A. , Chakrapani Venkatesan , Massaquoi Notisha , Williams Charmaine C. , Tharao Wangari , Tepjan Suchon , Roungprakhon Surachet , Forbes Joelleann , Sebastian Sarah , Akkakanjanasupar Pakorn , Aden Muna
Published: January 2023

Purpose

Lesbian, gay, bisexual, transgender, queer, and other persons outside of heteronormative and cisgender identities (LGBTQ+) and ethnic/racial minority populations are at heightened vulnerability amid the Covid-19 pandemic. Systemic marginalization and resulting adverse social determinants of health contribute to health disparities among these populations that result in more severe consequences due to Covid-19 and the public health measures to control it. We developed and tested a tailored online intervention (#SafeHandsSafeHearts) to support ethnoracially diverse LGBTQ+ individuals in Toronto, Canada amid the pandemic.

Methods

We used a quasi-experimental pre-test post-test design to evaluate the effectiveness of a 3-session, peer-delivered eHealth intervention in reducing psychological distress and increasing Covid-19 knowledge and protective behaviors. Individuals ≥18-years-old, resident in Toronto, and self-identified as sexual or gender minority were recruited online. Depressive and anxiety symptoms, Covid-19 knowledge and protective behaviors were assessed at baseline, 2-weeks postintervention, and 2-months follow-up. We used generalized estimating equations and zero-truncated Poisson models to evaluate the effectiveness of the intervention on the four primary outcomes.

Results

From March to November 2021, 202 participants (median age, 27 years [Interquartile rage: 23-32]) were enrolled in #SafeHandsSafeHearts. Over half (54%, n=110) identified as cisgender lesbian or bisexual women or women who have sex with women, 26.2% (n=53) cisgender gay or bisexual men or men who have sex with men, and 19.3% (n=39) transgender or nonbinary individuals. The majority (75.7%, n=143) were Black and other people of color. The intervention led to statistically significant reductions in the prevalence of clinically significant depressive and anxiety symptoms, and increases in Covid-19 protective behaviors from baseline to postintervention.

Conclusion

We demonstrated the effectiveness of a brief, peer-delivered eHealth intervention for ethnoracially diverse LGBTQ+ communities in reducing psychological distress and increasing protective behaviors amid the Covid-19 pandemic. Implementation through community-based health services with trained peer educators supports feasibility, acceptability, and the importance of engaging ethnoracially diverse LGBTQ+ communities in pandemic response preparedness. This trial is registered with ClinicalTrials.gov, numberNCT04870723.
Deep learning-based Segmentation of Multi-site Disease in Ovarian Cancer
Authors: Buddenkotte Thomas , Rundo Leonardo , Woitek Ramona , Sanchez Lorena Escudero , Beer Lucian , Crispin-Ortuzar Mireia , Etmann Christian , Mukherjee Subhadip , Bura Vlad , McCague Cathal , Sahin Hilal , Pintican Roxana , Zerunian Marta , Allajbeu Iris , Singh Naveena , Anju Sahdev , Havrilesky Laura , Cohn David E. , Bateman Nicholas W. , Conrads Thomas P. , Darcy Kathleen M. , Maxwell G. Larry , Freymann John B. , Öktem Ozan , Brenton James D. , Sala Evis , Schönlieb Carola-Bibiane
Published: January 2023

Purpose

To determine if pelvic/ovarian and omental lesions of ovarian cancer can be reliably segmented on computed tomography (CT) using fully automated deep learning-based methods.

Materials and Methods

A deep learning model for the two most common disease sites of high grade serous ovarian cancer lesions (pelvis/ovaries and omentum) was developed and compared against the well-established “no-new-Net” (nnU-Net) framework and unrevised trainee radiologist segmentations. A total of 451 pre-treatment and post neoadjuvant chemotherapy (NACT) CT scans collected from four different institutions were used for training (n=276), hyper-parameter tuning (n=104) and testing (n=71) of the methods. The performance was evaluated using the Dice similarity coefficient (DSC) and compared using a Wilcoxon test on paired results

Results

Our model outperforms the nnU-Net framework by a significant margin for both disease (validation: p=1×10-4,1.5×10-6, test: p=0.004, 0.005) and it does not perform significantly different from a trainee radiologist for the pelvic/ovarian lesions (p=0.392). On an independent test set (n=71), the model achieves a performance of 72±19 mean DSC for the pelvic/ovarian and 64±24 for the omental lesions.

Conclusion

Automated ovarian cancer segmentation on CT using deep neural networks is feasible and achieves performance close to a trainee-level radiologist for pelvic/ovarian lesions.

Deep learning-based models were used to assess whether fully automated segmentation is feasible for the main two disease sites in high grade serous ovarian cancer.

Key Points

First automated approach for pelvic/ovarian and omental ovarian cancer lesion segmentation on CT images.

Automated segmentation of ovarian cancer lesions can be comparable with manual segmentation of trainee radiologists with three years of experience in oncological and gynecological imaging.

Careful hyper-parameter tuning can provide models significantly outperforming strong state-of-the-art baselines.
Genomic landscape ofTP53-mutated myeloid malignancies
Authors: Abel Haley J. , Oetjen Karolyn A. , Miller Christopher A. , Ramakrishnan Sai M. , Day Ryan B. , Helton Nichole M. , Fronick Catrina C. , Fulton Robert S. , Heath Sharon E. , Tarnawsky Stefan P. , Srivatsan Sridhar Nonavinkere , Duncavage Eric J. , Schroeder Molly C. , Payton Jacqueline E. , Spencer David H. , Walter Matthew J. , Westervelt Peter , DiPersio John F. , Ley Timothy J. , Link Daniel C.
Published: January 2023

TP53-mutated myeloid malignancies are most frequently associated with complex cytogenetics. The presence of complex and extensive structural variants complicates detailed genomic analysis by conventional clinical techniques. We performed whole genome sequencing of 42 AML/MDS cases with paired normal tissue to characterize the genomic landscape ofTP53-mutated myeloid malignancies. The vast majority of cases had multi-hit involvement at theTP53genetic locus (94%), as well as aneuploidy and chromothripsis. Chromosomal patterns of aneuploidy differed significantly fromTP53-mutated cancers arising in other tissues. Recurrent structural variants affected regions that includeETV6on chr12p,RUNX1on chr21, andNF1on chr17q. Most notably forETV6, transcript expression was low in cases ofTP53-mutated myeloid malignancies both with and without structural rearrangements involving chromosome 12p. Telomeric content is increased inTP53-mutated AML/MDS compared other AML subtypes, and telomeric content was detected adjacent to interstitial regions of chromosomes. The genomic landscape ofTP53-mutated myeloid malignancies reveals recurrent structural variants affecting key hematopoietic transcription factors and telomeric repeats that are generally not detected by panel sequencing or conventional cytogenetic analyses.

Key Points

WGS comprehensively determinesTP53mutation status, resulting in the reclassification of 12% of cases from mono-allelic to multi-hit

Chromothripsis is more frequent than previously appreciated, with a preference for specific chromosomes

ETV6is deleted in 45% of cases, with evidence for epigenetic suppression in non-deleted cases

NF1is mutated in 48% of cases, with multi-hit mutations in 17% of these cases

TP53-mutated AML/MDS is associated with altered telomere content compared with other AMLs
Evaluating eating behaviour, energy homeostasis and obesity in childhood onset craniopharyngioma: A feasibility study
Authors: Hinton Elanor C. , Lithander Fiona E. , Elsworth Rebecca L. , Hawton Katherine , Narayan Kruthika , Szymkowiak Sophie , Bedford Holly L. , Naeem Nimra , Elson Ruth , Taylor-Miller Tashunka , Hamilton-Shield Julian P. , Crowne Elizabeth C.
Published: January 2023

Introduction

Craniopharyngiomas are rare brain tumours (incidence 1.1-1.7 cases/million/year). Although benign, craniopharyngioma causes major endocrine and visual morbidities including hypothalamic obesity, yet mechanisms leading to obesity are poorly understood. This study investigated the feasibility and acceptability of eating behaviour measures in patients with craniopharyngioma, to inform the design of future trials.

Methods

Patients with childhood-onset craniopharyngioma and controls matched for sex, pubertal stage and age were recruited. After an overnight fast, participants received the following measures: body composition, resting metabolic rate, oral-glucose-tolerance-test including MRI (patients only), appetite ratings, eating behaviour and quality of life questionnaires, ad libitum lunch, and an acceptability questionnaire. Data are reported as median ± IQR, with effect size measure (Cliff’s delta) and Kendall’s Tau for correlations, due to the small sample size.

Results

Eleven patients (median age=14yrs; 5F/6M) and matched controls (median age=12yrs; 5F/6M) were recruited. All patients had received surgery and 9/11 also received radiotherapy. Hypothalamic damage post-surgery was graded (Paris grading): grade 2 n=6; grade 1 n=1; grade 0 n=2. The included measures were deemed highly tolerable by participants and their parent/carers. Preliminary data suggests a difference in hyperphagia between patients and controls (d=0.5), and a relationship between hyperphagia with body mass index (BMISDS) in patients (τ=0.46).

Discussion

These findings demonstrate that eating behaviour research is feasible and acceptable to craniopharyngioma patients and there is an association between BMISDS and hyperphagia in patients. Thus, food approach and avoidance behaviours may be useful targets for interventions to manage obesity in this patient group.
ADHD and Autism Spectrum Disorder (ASD) in Childhood: establishing the feasibility and validity of a nation-wide e-cohort
Authors: Langley Kate , Pozo-Banos Marcos Del , Daalsgard Søren , Paranjothy Shantini , Riglin Lucy , John Ann , Thapar Anita
Published: January 2023

Objectives

We investigated the feasibility and validity of establishing a nationwide e-cohort of individuals with a diagnosis of ADHD and/or ASD for future longitudinal research.

Design

Individuals with a childhood diagnosis of ADHD/ASD as recorded on routinely available healthcare datasets were compared with matched controls and a sample of directly assessed individuals with ADHD.

Setting

This study utilised data from the Welsh Secure Anonymised Information Linkage (SAIL) Databank in Wales, UK. Routinely collected data from primary care, Emergency Department and hospital admissions were linked at person level.

Participants

All individuals in Wales, UK born between 01/01/1991 and 31/12/2000. Individuals with a recorded diagnosis of ADHD and/or ASD by age 18 years were identified using ICD-10 and NHS Read codes and matched to three controls each and 154 individuals with ADHD recruited from an established research study.

Outcome measures

Recorded service use for anxiety and depression, alcohol and drug use and self-harm including Emergency Department use in young adulthood (age 16 years to 25).

Results

7726 individuals had a recorded diagnosis of ADHD (80% male) and 5001 of ASD (79% male); % and 0.9% of the population respectively. Cox’s regression analyses showed ADHD was associated with increased risks of anxiety/depression (HR:2.36, 95% CI:2.20,2.53), self-harm (HR: 5.70, 95% CI:5.07,6.40), alcohol (HR:3.95, 95%CI:3.42,4.56), drug use (HR:5.88, 95%CI:5.08,6.80) and Emergency department service use (HR:1.36, 95%CI:1.31,1.41). Those with ASD were at increased risk of anxiety/depression (HR:2.11, 95%CI: 1.91,2.34), self-harm (HR:2.93, 95%CI: 2.45,3.50) and drug use (HR:2.21, 95%CI: 1.66,2.95) but not alcohol use. The ADHD e-cohort were similar to the directly assessed cohort.

Conclusions

Our identification strategy demonstrated the feasibility of establishing a large e-cohort of those with ADHD/ASD with expected patterns of poorer early adult outcomes, demonstrating a valid method of identifying large samples for future longitudinal studies without selective attrition.

Article summary

Strengths and limitations of this study

This study used population wide administrative data from a well-established and comprehensive databank

Data from both primary and secondary care was combined

The study utilised a directly assessed sample of those with ADHD to help validate the establishment of the administratively identified sample

Not all individuals had passed through the whole follow up period at the end of the study

Studies utilising administrative data is dependent upon that data having been collected an recorded.
THE ROLE OF KNOWLEDGE AND ATTITUDE ON HIV AND AIDS PREVENTION PRACTICES AMONG SECONDARY SCHOOL STUDENTS: A CROSS-SECTIONAL STUDY OF GWASSI SOUTH SUB-COUNTY, HOMA BAY COUNTY, KENYA
Authors: Akello Kennedy Odhiambo , Ogendi Japheths , Asweto Collins Otieno
Published: January 2023

Background

Homa Bay County HIV prevalence is the highest and 4.5 times the national prevalence. Young people aged 15-24 years account for 22% of this prevalence in the County. Majority of these young people are high school students, yet their knowledge, attitudes, practices and risk perception towards HIV prevention have not been unascertained. This could be one of the obstacles to HIV prevention in the county.

Objective

The study aimed at assessing HIV-related Knowledge, Attitudes and Practices (KAPs) of high school students in Homa Bay County.

Methodology

Survey was conducted among 260 systematically sampled students from 11 randomly selected schools in Gwassi South ward, Suba South sub-County, Homa Bay County. A head teacher or health master from each of the 11 schools was purposively sampled and took part in key informants’ interview about available strategies for HIV prevention. Data was analyzed using SPSS version 18.0. Proportion was used to determine knowledge, attitude, and risk perception among the students. Logistic regression was used determine association between knowledge, attitude towards HIV & AIDS and sexual practices.

Results

Majority (64%) of students had moderate to high knowledge on HIV & AIDS and exhibited positive attitude towards HIV & AIDS (61.1%). However, 15% to 25% of students reported to have engaged in a risky sexual practice. Higher to moderate knowledge had increased likelihood of positive attitude towards HIV and AIDS. Similarly, those with higher to moderate knowledge demonstrated lower risk sex practices. Moreover, students with negative attitude towards HIV & AIDS were 4 times more likely to have high risk sex practices. There were HIV & AIDS intervention strategies in secondary schools within Gwassi South Ward.

Conclusion

Knowledge and attitude of the students play a big role in their HIV risk perception as well as sex practices. Understanding knowledge, attitude, practice and intervention strategies of HIV and AIDS is significant in policy formulation by Ministries of Education, and leads to improved health-related practice by the Ministry of Health and researchers focusing on HIV and AIDS in high burden area.
Is platelet activation a link between metabolic syndrome and cognitive impairment in patients with schizophrenia?
Authors: Okusaga Olaoluwa O. , Vijayan K. Vinod , Rumbaut Rolando E.
Published: January 2023

Introduction

Schizophrenia is a severe psychiatric condition associated with cognitive impairment and premature dementia. Furthermore, metabolic syndrome (MetS)—combined central obesity, diabetes, dyslipidemia and hypertension—is highly prevalent in patients with schizophrenia and is believed to contribute to cognitive impairment and premature dementia in patients with schizophrenia. However, the mechanisms by which MetS contributes to cognitive impairment in patients with schizophrenia is unclear. Based on the association of MetS with platelet activation and the ability of activated platelets to impact blood-brain-barrier function, we tested the hypothesis that platelet activation is associated with both MetS and cognitive impairment in two independent pilot samples of patients with schizophrenia.

Methods

In the first pilot sample (sample A) we recruited 13 veterans with either schizophrenia or schizoaffective disorder with MetS (MetS+, n=6), and without MetS (MetS-, n=7). We administered the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) on all 13 veterans and assessed platelet activation using flow cytometry. In the second pilot sample (sample B), we identified 10 non-veteran MetS+ patients with schizophrenia and 10 age-, and sex-matched MetS-patients with schizophrenia from previously collected data on 106 patients enrolled in a non-MetS study. Participants in sample B had data on the NIH Toolbox cognitive battery (NIH Toolbox) and plasma soluble P-selectin (sP-selectin), a marker of platelet activation. We compared flow cytometry platelet activation in MetS+ and MetS- using the Mann Whitney test and the median test to compare sP-selectin and cognitive measures. We also measured the correlation between platelet activation and cognition using Spearman’s rho correlation.

Results

Platelet activation was significantly higher in MetS+ than MetS- (mean rank 8.60 vs. 3.83, p=0.017). Median score for the picture vocabulary test (language ability) was significantly lower in MetS+ relative to MetS- (82.35 vs. 104, p=0.015). In addition, platelet activation correlated negatively (rho = −0.74, p= 0.009) with the Wechsler Memory Scale: Spatial Span (nonverbal working memory) and plasma sP-selectin correlated negatively (rho = −0.55, p= 0.029) with the List Sorting Working Memory Test.

Conclusion

Our preliminary findings suggest that platelet activation is involved in the association of MetS with cognitive impairment in patients with schizophrenia. Future studies are needed to elucidate the role of platelets in MetS-related cognitive impairment in patients with schizophrenia.
MANF stimulates autophagy and restores mitochondrial homeostasis to treat toxic proteinopathy
Authors: Kim Yeawon , Li Chuang , Gu Chenjian , Tycksen Eric , Puri Anuradhika , Pietka Terri A. , Sivapackiam Jothilingam , Fang Yili , Kidd Kendrah , Park Sun-Ji , Johnson Bryce G. , Kmoch Stanislav , Duffield Jeremy S. , Bleyer Anthony J. , Jackrel Meredith E. , Urano Fumihiko , Sharma Vijay , Lindahl Maria , Chen Ying Maggie
Published: January 2023

Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), one of the leading hereditary kidney diseases, and Alzheimer’s disease etc. There are no targeted therapies. ADTKD is also a genetic form of renal fibrosis and chronic kidney disease, which affects 500 million people worldwide. For the first time, in our newly generated mouse model recapitulating human ADTKD-UMODcarrying a leadingUMODdeletion mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are severely impaired, leading to cGAS- STING activation and tubular injury. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel endoplasmic reticulum stress-regulated secreted protein. We provide the first study that inducible tubular overexpression of MANF after the onset of disease stimulates autophagy/mitophagy and clearance of the misfolded UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, resulting in protection of kidney function. Conversely, genetic ablation of endogenous MANF upregulated in the mutant mouse and human tubular cells worsens autophagy suppression and kidney fibrosis. Together, we discover MANF as a novel biotherapeutic protein and elucidate previously unknown mechanisms of MANF in regulating organelle homeostasis to treat ADTKD, which may have broad therapeutic application to treat various proteinopathies.
Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins
Authors: Cacciottolo Mafalda , Nice Justin B , Li Yujia , LeClaire Michael J. , Twaddle Ryan , Mora Ciana , Adachi Stephanie Y. , Chin Esther R. , Young Meredith , Angeles Jenna , Elliott Kristi , Sun Minghao
Published: January 2023

Current approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultra-low storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed which offer broader immunity but require significant time for development and use of an adjuvant to boost immune response. Here, exosomes were used to deliver a bi-valent protein-based vaccine, in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) or the more conserved nucleocapsid (Stealth X-Nucleocapsid, STX-N) protein on the surface. When administered as single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these results were obtained with administration of only nanograms of protein and without adjuvant. In two independent animal models (mouse and rabbit), administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike and strong T-cell responses. Importantly, no competition in immune response was observed, allowing for delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthXTMexosome platform has an enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low dose vaccine resulting in potent, broader immunity.
Nest site selection and productivity of a critically endangered parrot, the great green macaw (Ara ambiguus), in an anthropogenic landscape
Authors: Lewis Thomas C. , Gutiérrez Vargas Ignacio , Vredenbregt Claire , Jimenez Mario , Hatchwell Ben , Beckerman Andrew P. , Childs Dylan Z.
Published: January 2023

Nest site selection is the principal way secondary cavity-nesting species mitigate the negative effects of factors such as predation, parasitism and exposure on productivity. High-quality cavities could then be expected to be selected in response to the primary threat to nest success. Understanding how demographic rates are affected by anthropogenic changes to ecosystems is vital if effective conservation management strategies are to be developed and implemented. Large-bodied secondary cavity-nesting birds rely on large cavities in mature trees that are often absent or reduced in anthropogenically disturbed forests. Thus, the availability of high-quality nest sites may be limited for these species, potentially reducing productivity. The aim of this study was to investigate nest-site selection and the effect of nest-site features on productivity in the critically endangered great green macaw (Ara ambiguus) in northern Costa Rica. We show that great green macaws select nest sites according to the characteristics of the cavity and of the tree in which they are located. Moreover, productivity was a function of certain cavity features. We conclude that great green macaws are not reliant on primary forest for nest sites and typically choose cavities in remnant, isolated trees in pasture or young secondary forests.
Multimodal Data Integration Advances Longitudinal Prediction of the Naturalistic Course of Depression and Reveals a Multimodal Signature of Disease Chronicity
Authors: Habets Philippe C. , Thomas Rajat M , Milaneschi Yuri , Jansen Rick , Pool Rene , Peyrot Wouter J , Penninx Brenda WJH , Meijer Onno C , van Wingen Guido A , Vinkers Christiaan H.
Published: January 2023

The ability to individually predict disease course of major depressive disorder (MDD) is essential for optimal treatment planning. Here, we use a data-driven machine learning approach to assess the predictive value of different sets of biological data (whole-blood proteomics, lipid-metabolomics, transcriptomics, genetics), both separately and added to clinical baseline variables, for the longitudinal prediction of 2-year MDD chronicity (defined as presence of MDD diagnosis after 2 years) at the individual subject level. Prediction models were trained and cross-validated in a sample of 643 patients with current MDD (2-year chronicity n = 318) and subsequently tested for performance in 161 MDD individuals (2-year chronicity n = 79). Proteomics data showed best unimodal data predictions (AUROC = 0.68). Adding proteomic to clinical data at baseline significantly improved 2-year MDD chronicity predictions (AUROC = 0.63 vs AUROC = 0.78, p = 0.013), while the addition of other -omics data to clinical data did not yield significantly increased model performance. SHAP and enrichment analysis revealed proteomic analytes involved in inflammatory response and lipid metabolism, with fibrinogen levels showing the highest variable importance, followed by symptom severity. Machine learning models outperformed psychiatrists’ ability to predict two-year chronicity (balanced accuracy = 71% vs 55%). This study showed the added predictive value of combining proteomic, but not other -omic data, with clinical data. Adding other -omic data to proteomics did not further improve predictions. Our results reveal a novel multimodal signature of MDD chronicity that shows clinical potential for individual MDD disease course predictions from baseline measurements.
Steady-state polypeptide transfer from the translocon to the membrane
Authors: Knyazev Denis G. , Schaur Mirjam , Kuttner Roland , Siligan Christine , Gössweiner-Mohr Nikolaus , Hagleitner-Ertugrul Nora , Pohl Peter
Published: January 2023

In concert with irreversible non-equilibrium peptide translation by the ribosome, the nascent polypeptide chain may integrate into the membrane or translocate to the other side of the membrane, facilitated by the conserved protein translocation channel SecYEG in bacteria and Sec61 in eukaryotes. Assuming equilibrium for the decision processes yielded the biological hydrophobicity scale, reflecting free-energy differences ΔG between the pore interior and membrane. Yet kinetic effects and molecular dynamic simulations suggested that a nascent polypeptide could not sample the two separate environments a sufficient number of times for partitioning in equilibrium. Here we tested the hypothesis employing purified and reconstituted SecYEG harboring a stalled ribosome nascent chain (RNC). The SecYEG-RNC complex was open in a de-energized membrane, allowing ion flow. Application of a membrane potential closed the channel if nascent chain hydrophobicity permitted membrane integration. Taking the ratio of steady-state to initial ion conductances as a measure of nascent chain hydrophobicity, we found ΔG for KvAP’s voltage sensor (4thhelix harboring four arginines) and FtsQ’s transmembrane helix to be equal to 0.3 and –2.1 kcal/mol, respectively. Thus, ΔG observed in our minimalistic system agrees very well with the position-dependent amino acid contribution of the biological hydrophobicity scale. Characteristic sampling times of ~2 s appear sufficient to reach a steady state for a ~20 amino acid-long segment invalidating the hypothesis of insufficient sampling.
Next-generation diarylquinolines improve sterilizing activity of regimens with pretomanid and the novel oxazolidinone TBI-223 in a mouse tuberculosis model
Authors: Li Si-Yang , Converse Paul J. , Betoudji Fabrice , Lee Jin , Mdluli Khisimuzi , Upton Anna , Fotouhi Nader , Nuermberger Eric L.
Published: January 2023

A regimen comprised of bedaquiline, pretomanid and linezolid (BPaL) is the first oral 6-month regimen approved by the US Food and Drug Administration and recommended by the World Health Organization for treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines in early clinical trials, TBAJ-587 and TBAJ-876. We also evaluated the effect of replacing linezolid with a new oxazolidinone, TBI-223, exhibiting a larger safety margin with respect to mitochondrial toxicity in preclinical studies. Replacing bedaquiline with TBAJ-587 at the same 25 mg/kg dose significantly reduced the proportion of mice relapsing after 2 months of treatment, while replacing linezolid with TBI-223 at the same 100 mg/kg dose did not significantly change the proportion of mice relapsing. Replacing linezolid or TBI-223 with sutezolid in combination with TBAJ-587 and pretomanid significantly reduced the proportion of mice relapsing. In combination with pretomanid and TBI-223, TBAJ-876 at 6.25 mg/kg was equipotent to TBAJ-587 at 25 mg/kg. We conclude that replacement of bedaquiline with these more efficacious and potentially safer diarylquinolines and replacement of linezolid with potentially safer and at least as efficacious oxazolidinones in the clinically successful BPaL regimen may lead to superior regimens capable of treating both drug-susceptible and drug-resistant TB more effectively and safely.
SwissGenVar: A platform for clinical grade interpretation of genetic variants to foster personalized health care in Switzerland
Authors: Kraemer Dennis , Terumalai Dillenn , Famiglietti Maria Livia , Filges Isabel , Joset Pascal , Koller Samuel , Maurer Fabienne , Meier Stéphanie , Nouspikel Thierry , Sanz Javier , Zweier Christiane , Abramowicz Marc , Berger Wolfgang , Cichon Sven , Schaller André , Superti-Furga Andrea , Barbié Valérie , Rauch Anita
Published: January 2023

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows including the extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUS) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of standards used to describe genetic variants and associated phenotypes when searching for relevant information to inform clinical decision-making.

For this purpose, all five Swiss academic Medical Genetics Institutions joined forces with the Swiss Institute of Bioinformatics (SIB) to createSwissGenVaras a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its objective is to provide a protected environment for expert evidence sharing about individual variants to harmonize and up-scale their significance interpretation at clinical grade following international standards. To corroborate the clinical assessment, the variant-related data are combined with consented high-quality clinical information. Broader visibility will be gained by interfacing with international databases, thus supporting global initiatives in personalized health care.