bluuebunny/crossref_metadata_2025 huggingface dataset:
More youthful brain activations observed in older adults with better cognition
Authors: Gazes Yunglin , Argiris Georgette , Haynes Caleb R. , Stern Yaakov , Habeck Christian G.
Published: August 2023

We investigated factors that influence the maintenance of youthful functional activation for a working memory task in healthy older adults. While task-related functional activation has been found to increase in extent and intensity in aging, there have been few investigations into the factors that enable more youthful-appearing activation patterns. Similarity to young-like templates underlying more successful cognitive aging is an attractive idea and has been operationalized in a variety of different data domains in neuroscience. We applied an operationalization of such template similarity in a well-understood verbal working-memory task examined in 135 older adults (age=64.9 ± 3.17 years) using 44 younger adults (age=26.0 ± 2.9 years) as the reference group. Topographic similarity to the young-reference pattern was computed as spatial correlation across voxels between a young- and an older-group pattern. Similarity to the young-reference pattern was evaluated via two approaches: group-wise and at the individual level. In group-wise similarity, moderating factors were dichotomized, splitting older adults into two group. Examining the similarity between these group patterns and the young-reference pattern, we observed more youthful-appearing activation patterns for females than males, participants with thicker than thinner cortex, less white matter hyperintensity than more, and better performance in vocabulary, processing speed, memory, and reasoning. No difference in similarity was observed for high vs. low education groups. Individual-level similarity was quantified between the young-reference pattern template and each older adult’s pattern, for which linear regression showed that the degree of similarity to the young pattern was associated with more accurate performance on the working-memory task, even after covarying out age, sex, education, and three brain structural measures. Overall, using a novel approach to quantify topographic similarity between younger and older adults, we provided evidence that older adults with better overall cognition recruit more youthful-appearing activation patterns during working-memory rehearsal, and we discussed its relevance to resilience mechanisms in aging.
Analysis of Economic and Educational Spillover Effects in PEPFAR Countries
Authors: Crown William , Hariharan Dhwani , Kates Jennifer , Gaumer Gary , Jordan Monica , Hurley Clare L. , Luan Yiqun , Nandakumar A.K.
Published: August 2023

The United States President’s Emergency Plan for AIDS Relief (PEPFAR) has been credited with saving millions lives and helping to change the trajectory of the global human immunodeficiency virus (HIV) epidemic. This study assesses whether PEPFAR has had impacts beyond health by examining changes in five economic and educational outcomes in PEPFAR countries: the gross domestic product (GDP) per capita growth rate; the share of girls and share of boys, respectively, who are out of school; and female and male employment rates. We constructed a panel data set for 157 low- and middle-income countries between 1990 and 2018 to estimate the macroeconomic impacts of PEPFAR. Our PEPFAR group included 90 countries that had received PEPFAR support over the period. Our comparison group included 67 low- and middle-income countries that had not received any PEPFAR support or had received minimal PEPFAR support (<$1M or <$.05 per capita) between 2004 and 2018. We used differences in differences (DID) methods to estimate the program impacts on the five economic and educational outcome measures. This study finds that PEPFAR is associated with increases in the GDP per capita growth rate and educational outcomes. In some models, we find that PEPFAR is associated with reductions in male and female employment. However, these effects appear to be due to trends in the comparison group countries rather than programmatic impacts of PEPFAR. We show that these impacts are most pronounced in COP countries receiving the highest levels of PEPFAR investment.
Text mining biomedical literature to identify extremely unbalanced data for digital epidemiology and systematic reviews: dataset and methods for a SARS-CoV-2 genomic epidemiology study
Authors: Weissenbacher Davy , O’Connor Karen , Klein Ari , Golder Su , Flores Ivan , Elyaderani Amir , Scotch Matthew , Gonzalez-Hernandez Graciela
Published: August 2023

There are many studies that require researchers to extract specific information from the published literature, such as details about sequence records or about a randomized control trial. While manual extraction is cost efficient for small studies, larger studies such as systematic reviews are much more costly and time-consuming. To avoid exhaustive manual searches and extraction, and their related cost and effort, natural language processing (NLP) methods can be tailored for the more subtle extraction and decision tasks that typically only humans have performed. The need for such studies that use the published literature as a data source became even more evident as the COVID-19 pandemic raged through the world and millions of sequenced samples were deposited in public repositories such as GI-SAID and GenBank, promising large genomic epidemiology studies, but more often than not lacked many important details that prevented large-scale studies. Thus, granular geographic location or the most basic patient-relevant data such as demographic information, or clinical outcomes were not noted in the sequence record. However, some of these data was indeed published, but in the text, tables, or supplementary material of a corresponding published article. We present here methods to identify relevant journal articles that report having produced and made available in GenBank or GISAID, new SARS-CoV-2 sequences, as those that initially produced and made available the sequences are the most likely articles to include the high-level details about the patients from whom the sequences were obtained. Human annotators validated the approach, creating a gold standard set for training and validation of a machine learning classifier. Identifying these articles is a crucial step to enable future automated informatics pipelines that will apply Machine Learning and Natural Language Processing to identify patient characteristics such as co-morbidities, outcomes, age, gender, and race, enriching SARS-CoV-2 sequence databases with actionable information for defining large genomic epidemiology studies. Thus, enriched patient metadata can enable secondary data analysis, at scale, to uncover associations between the viral genome (including variants of concern and their sublineages), transmission risk, and health outcomes. However, for such enrichment to happen, the right papers need to be found and very detailed data needs to be extracted from them. Further, finding the very specific articles needed for inclusion is a task that also facilitates scoping and systematic reviews, greatly reducing the time needed for full-text analysis and extraction.
IntronicFGF14GAA repeat expansions are a common cause of downbeat nystagmus syndromes: frequency, phenotypic profile, and 4-aminopyridine treatment response
Authors: Pellerin David , Heindl Felix , Wilke Carlo , Danzi Matt C. , Traschütz Andreas , Ashton Catherine , Dicaire Marie-Josée , Cuillerier Alexanne , Del Gobbo Giulia , Boycott Kym M. , Claassen Jens , Rujescu Dan , Hartmann Annette M. , Zuchner Stephan , Brais Bernard , Strupp Michael , Synofzik Matthis
Published: August 2023

The cause of downbeat nystagmus (DBN) remains unknown in approximately 30% of patients (idiopathic DBN). Here, we hypothesized that: (i)FGF14(GAA)≥250repeat expansions represent a frequent genetic cause of idiopathic DBN syndromes, (ii) are treatable with 4-aminopyridine (4-AP), and (iii)FGF14(GAA)200-249alleles are potentially pathogenic.

We conducted a multi-modal cohort study of 170 patients with idiopathic DBN that comprised: in-depth ocular motor, neurological, and disease evolution phenotyping; assessment of 4-AP treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomized double-blind 4-AP trial; and genotyping of theFGF14repeat.

Frequency ofFGF14(GAA)≥250expansions was 48% (82/170) in the entire idiopathic DBN cohort. Additional cerebellar ocular motor signs were observed in 100% (82/82), cerebellar ataxia in 43% (35/82), and extracerebellar features in 21% (17/82) of (GAA)≥250-FGF14patients. Alleles of 200 to 249 GAA repeats were enriched in patients with DBN (12%; 20/170) compared to controls (0.87%; 19/2,191; OR, 15.20; 95% CI, 7.52-30.80;p=9.876e-14). The phenotype of (GAA)200-249-FGF14patients closely mirrored that of (GAA)≥250-FGF14patients. (GAA)≥250-FGF14and (GAA)200-249-FGF14patients had a significantly greater clinician-reported (80% vs 31%;p=0.0011) and self-reported (59% vs 11%;p=0.0003) response rate to 4-AP treatment compared to (GAA)<200-FGF14patients. This included a treatment response with high relevance to everyday living, as exemplified by an improvement of 2 FARS stages in some cases. Placebo-controlled video-oculography data of four (GAA)≥250-FGF14patients previously enrolled in a 4-AP randomized double-blind trial showed a significant decrease in slow phase velocity of DBN with 4-AP, but not placebo.

This study shows thatFGF14GAA repeat expansions are a highly frequent genetic cause of DBN syndromes, especially when associated with additional cerebellar features. Moreover, they genetically stratify a subgroup of patients with DBN that appear to be highly responsive to 4-AP, thus paving the way for a “theranostics” approach in DBN syndromes.
Dissecting the Genetic Architecture of Intracranial Aneurysms
Authors: Adkar Shaunak S. , Lynch Julie , Choi Ryan B. , Roychowdhury Tanmoy , Judy Renae L. , Paruchuri Kaavya , Go Dong-Chuan , Bamezai Sharika , Cabot John , Sorondo Sabina , Levin Michael G. , Milewicz Dianna M. , Willer Cristen J. , Natarajan Pradeep , Pyarajan Saiju , Chang Kyong-Mi , Damrauer Scott , Tsao Phil , Skirboll Stephen , Leeper Nicholas J. , Klarin Derek
Published: August 2023

Background

The genetic risk of intracranial aneurysm (IA) development has been ascribed largely to the genetic risk of smoking exposure and hypertension. However, the relationship of IA to other cardiovascular traits and the contribution of IA risk loci to aberrant gene programs within cerebrovascular cell types remains unclear.

Methods

We performed a genome-wide association study in the Million Veteran Program testing association of roughly 25 million DNA variants with unruptured IA (3,165 cases and 592,927 controls) in veterans of European, African, and Hispanic ancestries. This was meta-analyzed with publicly available summary statistics to yield a final cohort of 15,438 cases and 1,183,973 controls. Candidate causal genes were prioritized through expression quantitative trait loci colocalization, fine-mapping transcriptome wide association studies, and multi-trait colocalization. We constructed a cerebrovascular single nucleus RNA sequencing (snRNA-seq) dataset and integrated IA summary statistics to prioritize candidate causal cell types. We then constructed a polygenic risk score to identify patients at greater risk of developing IA.

Results

We identified five novel loci association with IA, increasing the number of known susceptibility loci to 22. At these susceptibility loci, we prioritized 16 candidate causal genes. Amongst other cardiovascular traits, we found a significant positive genetic correlation of IA with coronary artery disease and abdominal aortic aneurysm, and we identified 13 IA risk loci that colocalize with aneurysmal, atherosclerotic, and blood pressure traits. Integration of an IA gene set with human cerebrovascular snRNA-seq data revealed significant association with matrix-producing pericytes, smooth muscle cells (SMCs), and other mural subtypes. In addition, gene expression analysis revealed enrichment of several candidate genes within SMCs and pericytes. Finally, a high polygenic risk score (PRS) was significantly associated with IA across European (OR: 1.87, CI: 1.61-2.17, P = 8.8 × 10−17), African (OR: 1.62, CI: 1.19-2.15, P = 1.2 × 10−3), and Hispanic (OR: 2.28, CI: 1.47-3.38, P = 1.0 × 10−4) ancestries.

Conclusion

Here, we identify five novel loci associated with IA. Integration of summary statistics with cerebrovascular snRNA-seq reveals association of cell-types involved in matrix production. We constructed and validated a PRS that predicts IA, while controlling for demographic variables including smoking status, sex, and blood pressure. Taken together, our findings suggest that an intrinsic deficit in matrix production and vascular integrity may drive IA pathogenesis independent of systemic hypertension and smoking exposure.
Pharmacotherapy for Children and adolescents with overweight and obesity: a systematic review and network meta-analysis of randomized controlled trials
Authors: Luo Li , Huang Tingting , Wang Hui , Zhao Jianglin , Qi Yunyun , Yan Zijing , Zhu Chunmei , Wang Chufeng , Su Na , Xu Ting , Zhang Shengzhao
Published: August 2023

Background

Overweight and obesity are widespread among children and adolescents. We aimed to summarize the evidence for the pharmacotherapy as an adjunct to lifestyle interventions in overweight or obese children and adolescents by comparing the benefits and harms.

Methods

RCTs (randomized controlled trials) were sourced from PubMed, Embase (using the OVID platform), the Cochrane Library (CENTRAL), as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to April 25, 2023. A network meta-analysis was performed using the frequentists framework based on random-effects model. We used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the overall certainty of evidence and categorized the interventions.

Results

In total, 42 RCTs (n=3883) comparing 8 different pharmacotherapy strategies were included in this study. Evidence strongly suggested that phentermine-topiramate reduced BMI the most (the mean difference (MD) -4.83 [95% CI, -7.46 to -2.20] kg/m2) and weight (MD, -14.59 [95% CI, -19.37, -9.81] kg) in children and adolescents with overweight or obesity. Compared to lifestyle intervention alone, phentermine-topiramate was associated with an additional 557 events per 1000 person-years in terms of the proportion of participants achieving a BMI reduction of ≥5%, but there was no increased harm in total gastrointestinal adverse effects and discontinuation due to adverse events.

Conclusions

Phentermine-topiramate was closely related to weight loss and showed a good tolerability, proving to be the optimal treatment strategy for overweight or obese children and adolescents.

Registration

PROSPERO registry number: CRD42022329226
A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson’s disease and dementia with Lewy bodies
Authors: Bhome R , Verdi S , Martin SA , Hannaway N , Dobreva I , Oxtoby NP , Leal G Castro , Rutherford S , Marquand AF , Weil RS , Cole JH
Published: August 2023

INTRODUCTION

Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns and common group-average analyses are limited in capturing individual differences. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort.

METHODS

We generated z-scores from T1w-MRI scans for each participant (108 PD; 61 DLB) relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n=58,836). Outliers (z<-1.96) were aggregated across 169 brain regions per participant. We examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition.

RESULTS

We found greater total outlier counts in PD poor visual performers, compared to high; and in DLB versus PD. Outlier counts were associated with global cognition in DLB, and visuoperception in PD.

DISCUSSION

Neuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB.
Adaptive health technology assessments to inform oncology based priority setting in India
Authors: Ghosh Srobana , Pramesh C S , Sengar Manju , Ranganathan Priya , Nemzoff Cassandra , Ruiz Francis , Wadasadawala Tabassum , Nayak Prakash , Thorat Jayashree , Ashok Apurva , Singh Malkeet , Mehndiratta Abha , Shah Hiral Anil
Published: August 2023

Background

Health technology assessment (HTA) is a valuable tool for informing the most efficient allocation of resources, yet is highly resource intensive limiting its applicability in practice. Adapting the HTA process by leveraging available international evidence offers a pragmatic solution to such challenges, saving time whilst still generating useful insight for decision making.

Objective

To develop an adaptive HTA (aHTA) framework that could be used to assess the likely cost-effectiveness of cancer treatments to inform the available entitlements under the Indian national health insurance scheme.

Methods

The International Decision Support Initiative worked with the National Cancer Grid in India to develop an aHTA framework which included topic selection, scoping, evidence review and appraisal to estimate the likely cost-effectiveness of cancer interventions. The evidence included international data on cost effectiveness (HTA reports and economic evaluations), price benchmarking and treatment cost estimates. Ten interventions were assessed with the newly developed framework by a working group of clinicians and health economists from both institutions.

Results

Of 10 interventions assessed, 9 had sufficient evidence to decide cost-effectiveness; 3 were cost-effective (1 only after a discount, 1 using the generic price), 5 were not and 1 was not cost-effective for all but was in a subgroup. A full HTA was recommended for one intervention due to uncertainty. Information on the likely cost-effectiveness, clinical benefits and treatment costs was consistently available through publicly available evidence. India on average paid almost 4 times the list price of other countries.

Conclusion

aHTA provides an alternative to using no economic evidence at all if a full HTA cannot be conducted. It is well-suited to cancer drugs for which there is ample available international information on cost-effectiveness. Our framework quickly generated consistent, transparent evidence to inform guidelines. The approach may be replicable in other settings in supplement to full HTA.

Key messages

What is already known on this topic

There is an enormous need for more evidence informed priority setting, however there are often significant challenges to doing so such as insufficient data, capacity and resources available. Some countries are exploring the use of rapid or adaptive methods of health technology assessment (HTA) but there is no clear guidance on the methodology that should be used.

What this study adds

Experience of the results of an adaptive HTA framework in practice, based on 10 oncology problems.

How this study might affect research, practice or policy

Other countries or institutions with limited capacity for HTA could potentially use the framework to perform their own adaptive HTA assessments.
Estimating the effect of circulating vitamin D on body mass index: a Mendelian randomization study
Authors: Chadha Minal , Bell Joshua A. , Sanderson Eleanor
Published: August 2023

Background

Numerous observational studies have shown an association between higher circulating 25 hydroxyvitamin D (vitamin D) and lower body mass index (BMI). Whether this represents a causal effect remains unclear. Mendelian randomization (MR) is an approach to causal inference that uses genetic variants as instrumental variables to estimate the effect of exposures on outcomes of interest. MR estimates are not biased by confounding, reverse causation and other biases in the same way as conventional observational estimates. In this study, we used MR with new data on genetic variants associated with vitamin D to estimate the effect of vitamin D on BMI.

Methods

We selected single nucleotide polymorphisms (SNPs) which were associated with vitamin D in a recent large genome-wide association study (GWAS) at genome-wide significance as instruments for vitamin D. We used inverse variance weighted models and further assessed individual SNPs that showed evidence of an effect, and biologically informed SNPs located in genetic regions previously associated with vitamin D, for associations with other traits at genome-wide significance, using Wald ratio estimation.

Result

Our main results showed no evidence of an effect of vitamin D on BMI (estimated standard deviation change in BMI per standard deviation change in vitamin D: -0.003, 95% confidence interval [-0.06, 0.06]). This was also supported by pleiotropy robust sensitivity analyses. Individual SNPs that showed evidence of an effect of vitamin D on either lower or higher BMI were strongly associated with numerous other traits suggesting high levels of horizontal pleiotropy. Biologically informed SNPs showed no evidence of a causal effect of vitamin D on BMI and showed substantially less evidence of pleiotropic effects.

Conclusion

The observed association between vitamin D and BMI is unlikely to be due to a causal effect of vitamin D on BMI. We also show how additional evidence can be incorporated into an MR study to interrogate individual SNPs for potential pleiotropy and improve interpretation of results.
Patient-Reported Reasons for Antihypertensive Medication Change: A Quantitative Study Using Social Media
Authors: Micale Cristina , Golder Su , O’Connor Karen , Weissenbacher Davy , Gross Robert , Hennessy Sean , Gonzalez-Hernandez Graciela
Published: August 2023

Introduction

Hypertension is the leading cause of heart disease in the world, and discontinuation or nonadherence of antihypertensive medication constitutes a significant global health concern. Patients with hypertension have high rates of medication nonadherence [13–15]. Studies of reasons for nonadherence using traditional surveys are limited, can be expensive, and suffer from response, white-coat, and recall biases. Mining relevant posts by patients on social media is inexpensive and less impacted by the pressures and biases of formal surveys, which may provide direct insights into factors that lead to non-compliance with antihypertensive medication.

Methods

This study examined medication ratings posted to WebMD, an online health forum that allows patients to post medication reviews. We used a previously developed natural language processing classifier to extract indications and reasons for changes in angiotensin receptor II blocker (ARBs) and angiotensin-converting enzyme inhibitor (ACEIs) treatments. After extraction, ratings were manually annotated and compared to data from the FAERS public database.

Results

From a collection of 343,459 WebMD reviews, we automatically extracted 1,867 posts mentioning changes in ACEIs or ARBs, and manually reviewed the 300 most recent posts regarding ACEI treatments and the 300 most recent posts regarding ARB treatments. After excluding posts that only mentioned a dose change or were a false positive mention, 142 posts in the ARBs dataset and 187 posts in the ACEIs dataset remained. The majority of posts (97% ARBs, 91% ACEIs) indicated experiencing an adverse event as the reason for medication change. The most common adverse events reported mapped to the Medical Dictionary for Regulatory Activities were “musculoskeletal and connective tissue disorders” like muscle and joint pain for ARBs, and “respiratory, thoracic, and mediastinal disorders” like cough and shortness of breath for ACEIs. These categories also had the largest differences in percentage points, appearing more frequently on WebMD data than FDA data (p=0.000).

Conclusion

Musculoskeletal and respiratory symptoms were the most commonly reported adverse effects in social media postings associated with drug discontinuation. Managing such symptoms is a potential target of interventions seeking to improve medication persistence.

Key Points

The major reason for the discontinuation of ARBs and ACEIs expressed through WebMD was the experience of adverse events.

Musculoskeletal and respiratory symptoms were the most commonly reported adverse effects in social media postings associated with drug discontinuation.

This study shows the promise of WebMD mining as an effective tool in medication nonadherence and adverse event research.
A multi-database based ceRNA regulatory network for gastric cancer prognosis
Authors: Yin Long-Kuan , Li Qian
Published: August 2023

Objective

Circular RNA(circRNA) is a kind of endogenous non-coding RNA, which may be related to the occurrence and development of cancer. Based on the GEO database, this paper constructs a circRNA as a competitive endogenous RNAs(ceRNAs) that binds with microRNAs (miRNAs) to affect and regulate the expression of target genes. The ceRNA regulatory network based on circRNA-miRNA-mRNA model plays an important role in tumor prognosis and treatment. This paper explores the mechanism of circRNA-related ceRNA regulatory network in gastric cancer.

Method

CircRNA, miRNA and mRNA data sets related to gastric cancer were downloaded from The Gene Expression Omnibus (GEO), and the limma package of R software (R 4.2.1 version) was used to identify the differences between gastric cancer tissues and adjacent normal tissues of gastric cancer. DEcircRNA, DEmiRNAs, and DEmRNAs. Based on circBase database, we explored the interactions among circRNA, miRNA and mRNA, and constructed the circRNA-miRNA-mRNA ceRNA network by using Cytoscape_v3.8.0. Then KEGG, GO and survival analysis of ceRNA-related genes were performed. Then, the prognostic data of gastric cancer were extracted from the TCGA database to construct the prognostic subnetwork of gastric cancer.

Results

KEGG analysis of ceRNA’s mRNA showed that the pathway was mainly enriched in IL-17 signaling pathway, TNF signaling pathway and so on, which affected the prognosis of gastric cancer. hsa_circ_0055521/hsa-miR-204-5p/FAP, (hsa_circ_0005051, hsa_circ_0007613, hsa_circ_0045602, hsa_circ_0034398, hsa_circ_0006089) /hsa-miR-32-3p/FNDC1 were the ceRNA networks related to the prognosis of gastric cancer collaterals.

Conclusion

This study found that IL-17 signaling pathway and TNF signaling pathway may affect the occurrence, development and prognosis of gastric cancer. And hsa_circ_0055521/hsa-miR-204-5p/FAP, (hsa_circ_0005051, hsa_circ_0007613, hsa_circ_0045602, hsa_circ_0034398, hsa_circ_0006089) /hsa-miR-32-3p/FNDC1 two circrNa-based stomachs The cancer ceRNA prognostic network is a new prognostic related ceRNA network for gastric cancer. FNDC1 and FAP may be potential therapeutic targets for gastric cancer.
Linear age-course association between non-alcoholic fatty liver disease, components of metabolic syndrome, and mortality
Authors: Zhao Xinyu , Chen Shuohua , Wang Xiao mo , Wang Zhenyu , Sun Yuanyuan , Yang Chenlu , Zheng Mengyi , Wang Yanhong , Liao Wei , Wu Shouling , Wang Li
Published: August 2023

Background

The study aimed to explore the relationship between non-alcoholic fatty liver disease (NAFLD) and mortality by age and metabolic syndrome (MetS) components.

Method

We enrolled 104,173 participants in the Kailuan cohort from June 2006 through October 2013. Cox regression models were used to evaluate the hazard ratio (HR) and 95% confidence interval (CI). Population-attributable fractions (PAFs) of metabolic components were also calculated.

Results

Compared with non-NAFLD, the excess risk of all-cause and cardiovascular disease (CVD)-related mortality in NAFLD increased with the number of MetS components but decreased with age. The highest all-cause and CVD-related death risks were observed in NAFLD aged 18-39 with 4-5 MetS (HR=2.81, 95% CI:1.55-5.08) and those aged 40-49 years with 3 MetS (HR=2.25, 95% CI:1.55-5.08), respectively. However, there was no significant extra risk of liver-related death in NAFLD patients of any age. For PAF, 28.5% of all-cause and 43.4% of CVD-related mortality among NAFLD patients was preventable by controlling MetS components < 2, with the highest PAF in those aged 50-69 and 18-49, respectively. Elevated blood pressure (PAF of 24.7% for all-cause; 38.6% for CVD-related), elevated fasting glucose (PAF of 13.4% all-cause; 9.2% CVD-related), and elevated triglycerides (PAF of 3.9% all-cause; 14.0% CVD-related) were the essential mortality contributors in NAFLD participants.

Conclusion

The excess risk of all-cause and CVD-related mortality in NAFLD patients decreases with age. A substantial proportion of risks could be averted if NAFLD patients are controlled under two MetS components, especially managing blood pressure, fasting glucose, and triglycerides for the young.
Health care seeking behaviour for common menstrual problems and their determinants in Adolescent girls at rural setting in Central India: A mix-method study
Authors: Patel S , Patel B , Pushpalatha K , Halder A , Modi JN , Singh B
Published: August 2023

Introduction

Menstrual problems among adolescent females are common and a significant source of morbidity in this population.This study was to collect data on the different health seeking behaviours used by adolescents and their determinants for common menstrual illness in rural population in central India. Collected information may be vital for the development of appropriate adolescent healthcare system.

Aims & Objectives

To assess the health care seeking behaviour and factors determinants in adolescent girl/ their parents for menstrual problems in rural areas ofBhopal.

Material & Methods

This cross sectional study was done in nearby (within 30km radius of AIIMS Bhopal) schools villages on adolescent girls (12-19 years) after excluding the chronic illnesses. By using multistage cluster sampling 10 village schools were selected randomly. After taking informed consent from the head of the school 40 girls from each school were enrolled. The information were collected using a pre tested, semi structured questionnaire from all 400 participants. Statistical analysis was done by using IBM-SPSS version 22 software.

Results

The mean age of the girls in the study was 17±1.4 years. In our study 27% of adolescent girls suffered from menstrual problems with dysmenorrhoea (48%) was the most frequent complaint out of which nearly one-third of adolescent girls sought treatment. Majority (67%) girls didn’t know about menstruation prior to menarche. Social barriers/ restrictions, shame and misconceptions with the menstruations were commonly reported in these girls.

Conclusion

Adolescent girls are reluctant to seek medical advice and with little knowledge on adolescent’s health-seeking behavior towards the menstrual problems leading to delay in the diagnosis and treatment. Adolescent health educational programmes in the society and in the schools help the girls toimprove the treatment-seeking for menstrual problems, specifically in rural areas.
Toward adoption of health risk assessment in population-based and clinical scenarios
Authors: Gonzalez-Colom Ruben , Monterde David , Papa Roberta , Kull Mart , Anier Andres , Balducci Francesco , Cano Isaac , Coca Marc , De Marco Marco , Franceschini Giulia , Hinno Saima , Pompili Marco , Vela Emili , Piera-Jiménez Jordi , Pérez Pol , Roca Josep
Published: August 2023

Introduction

Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This report analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020–2023).

Description

The implementation research approach involved a twelve-month pre-implementation period to assess feasibility and define the local action plans, followed by a sixteen-month implementation phase. During the two periods, a well-defined combination of experience-based co-design and quality improvement methodologies were applied.

Discussion

The evolution of the Catalan HRA strategy (2010–2023) illustrates its potential for health systems transformation, as well as its transferability. The main barriers and facilitators for HRA adoption were identified. The report proposes a set of key steps to facilitate site customized deployment of HRA contributing to define a roadmap to foster large-scale adoption across Europe.

Conclusions

Successful adoption of the AMG algorithm was achieved in the two sites confirming transferability. Marche identified the key requirements for a population-based HRA strategy, whereas Viljandi Hospital proved its potential for clinical use paving the way toward value-based healthcare strategies.
Universal PCR for Bacteria, Mycobacteria, and Fungi: A 10-year Retrospective Review of Clinical Indications and Patient Outcomes
Authors: Kubiak Jeffrey , Morgan Alexandra , Kirmaier Andrea , Arnaout Ramy , Riedel Stefan
Published: August 2023

Universal PCR for bacteria, mycobacteria, and fungi can aid in the diagnosis of occult infections, especially in the case of fastidious organisms or when prior antimicrobial treatment compromises culture growth. However, the limitations of this technology, including lack of specificity, high cost, long turnaround time, and lack of susceptibility data, may limit its effect on clinical outcomes. We performed a retrospective analysis of all specimens sent for universal PCR over a 10-year period from 2013-2022, focusing on clinical indications for test utilization and patient outcomes. A total of 708 specimens were sent from 638 patients. Of those specimens, 163 were positive, for an overall positivity rate of 23%. Pre-analytic factors associated with a positive universal PCR result were the presence of organisms on Gram stain or histology, the presence of neutrophils on Gram stain, and growth on culture. Positivity rates varied significantly by specimen type. 20% of all organisms detected were deemed contaminants by the clinical services. A positive universal PCR led to a change in antibiotic management in 29% of cases. Positive fungal universal PCR results sent from hospitalized patients were associated with worse outcomes, including increased hospital mortality. Our findings suggest that factors such as the presence of organisms or neutrophils on Gram stain, specimen source/clinical context, and anticipated changes in management based on results should be strongly considered when making stewardship decisions regarding the appropriateness of this testing modality.
Integrating Genome-wide information and Wearable Device Data to Explore the Link of Anxiety and Antidepressants with Heart Rate Variability
Authors: Friligkou Eleni , Koller Dora , Pathak Gita A. , Miller Edward J. , Lampert Rachel , Stein Murray B. , Polimanti Renato
Published: August 2023

Background

Anxiety disorders are associated with decreased heart rate variability (HRV), but the underlying mechanisms remain elusive.

Methods

We selected individuals with whole-genome sequencing, Fitbit, and electronic health record data (N=920; 61,333 data points) from the All of Us Research Program. Anxiety PRS were derived with PRS-CS after meta-analyzing anxiety genome-wide association studies from three major cohorts-UK Biobank, FinnGen, and the Million Veterans Program (N Total =364,550). The standard deviation of average RR intervals (SDANN) was calculated using five-minute average RR intervals over full 24-hour heart rate measurements. Antidepressant exposure was defined as an active antidepressant prescription at the time of the HRV measurement in the EHR. The associations of daily SDANN measurements with the anxiety PRS, antidepressant classes, and antidepressant substances were tested. Participants with lifetime diagnoses of cardiovascular disorders, diabetes mellitus, and major depression were excluded in sensitivity analyses. One-sample Mendelian randomization (MR) was employed to assess potential causal effect of anxiety on SDANN.

Results

Anxiety PRS was independently associated with reduced SDANN (beta=-0.08; p=0.003). Of the eight antidepressant medications and four classes tested, venlafaxine (beta=-0.12, p=0.002) and bupropion (beta=-0.071, p=0.01), tricyclic antidepressants (beta=-0.177, p=0.0008), selective serotonin reuptake inhibitors (beta=-0.069; p=0.0008) and serotonin and norepinephrine reuptake inhibitors (beta=-0.16; p=2×10−6) were associated with decreased SDANN. One-sample MR indicated an inverse effect of anxiety on SDANN (beta=-2.22, p=0.03).

Conclusions

Anxiety and antidepressants are independently associated with decreased HRV, and anxiety appears to exert a causal effect on HRV. Our observational findings provide novel insights into the impact of anxiety on HRV.
Genomic investigation of multi-species and multi-variant blaNDM outbreak reveals key role of horizontal IncN and IncX3 plasmid transfer
Authors: Macesic Nenad , Dennis Adelaide , Hawkey Jane , Vezina Ben , Wisniewski Jessica A. , Cottingham Hugh , Blakeway Luke V. , Harshegyi Taylor , Pragastis Katherine , Badoordeen Gnei Zweena , Bass Pauline , Stewardson Andrew J. , Dennison Amanda , Spelman Denis W. , Jenney Adam W.J. , Peleg Anton Y.
Published: August 2023

Objectives

New Delhi metallo-beta-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel but from 2019 we noted increasing NDM episodes. We conducted an investigation to determine the clinical and genomic epidemiology of NDM-carriage at a tertiary Australian hospital from 2016-2021.

Methods

We identified 49 patients with 84 NDM-carrying isolates in an institutional database and collected clinical data from electronic medical records. Short- and long-read whole genome sequencing was performed on all isolates. Completed genome assemblies were used to assess the genetic setting ofblaNDMgenes and compare NDM plasmids.

Results

Of 49 patients, 38 (78%) were identified in 2019-2021 and only 11/38 (29%) reported prior travel compared with 9/11 (82%) in 2016-2018 (P=0.037). In patients with NDM infection, crude 7-day mortality was 0% and 30-day mortality was 14% (2/14 patients). NDMs were noted in 41 bacterial strains (i.e. species/sequence type combinations). Four NDM variants (blaNDM-1,blaNDM-4,blaNDM-5,blaNDM-7) were detected across 13 plasmid groups. We noted a change from a diverse NDM plasmid repertoire in 2016-2018 to the emergence of conservedblaNDM-1IncN andblaNDM-7IncX3 epidemic plasmids with inter-strain spread in 2019-2021. These plasmids were noted in 19/38 (50%) patients and 35/68 (51%) genomes in 2019-2021.

Conclusions

Increased NDM case numbers were due to local circulation of two epidemic plasmids with extensive inter-strain transfer. Our study underscores the challenges of outbreak detection when horizontal transmission of plasmids is the primary mode of spread.
Facilitating youth diabetes studies with the most comprehensive epidemiological dataset available through a public web portal
Authors: McDonough Catherine , Li Yan Chak , Vangeepuram Nita , Liu Bian , Pandey Gaurav
Published: August 2023

The prevalence of type 2 diabetes mellitus (DM) and prediabetes (preDM) is rapidly increasing among youth, posing significant health and economic consequences. To address this growing concern, we created the most comprehensive youth-focused diabetes dataset to date derived from National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. The dataset, consisting of 15,149 youth aged 12 to 19 years, encompasses preDM/DM relevant variables from sociodemographic, health status, diet, and other lifestyle behavior domains. An interactive web portal, POND (Prediabetes/diabetes in youth ONline Dashboard), was developed to provide public access to the dataset, allowing users to explore variables potentially associated with youth preDM/DM. Leveraging statistical and machine learning methods, we conducted two case studies, revealing established and lesser-known variables linked to youth preDM/DM. This dataset and portal can facilitate future studies to inform prevention and management strategies for youth prediabetes and diabetes.
Real-time epidemiological modelling during the COVID-19 emergency in Wales
Authors: Gravenor Mike B , Dawson Mark , Bennett Ed , Thorpe Ben , White Carla , Rahat Alma , Archambault Daniel , Picco Noemi , Powathil Gibin , Lucini Biagio
Published: August 2023

The sudden outbreak of the COVID-19 pandemic presented governments, policy makers and health services with an unprecedented challenge of taking real-time decisions that could keep the disease under control with non-pharmaceutical interventions, while at the same time limit as much as possible severe consequences of a very strict lockdown. Mathematical modelling has proved to be a crucial element for informing those decisions. Here we report on the rapid development and application of the Swansea Model, a mathematical model of disease spread in real time, to inform policy decisions during the COVID-19 pandemic in Wales.
Strong protective effect of theAPOL1p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
Authors: Gupta Yask , Friedman David J. , McNulty Michelle , Khan Atlas , Lane Brandon , Wang Chen , Ke Juntao , Jin Gina , Wooden Benjamin , Knob Andrea L. , Lim Tze Y. , Appel Gerald B. , Huggins Kinsie , Liu Lili , Mitrotti Adele , Stangl Megan C. , Bomback Andrew , Westland Rik , Bodria Monica , Marasa Maddalena , Shang Ning , Cohen David J. , Crew Russell J. , Morello William , Canetta Pietro , Radhakrishnan Jai , Martino Jeremiah , Liu Qingxue , Chung Wendy K. , Espinoza Angelica , Luo Yuan , Wei Wei-Qi , Feng Qiping , Weng Chunhua , Fang Yilu , Kullo Iftikhar J. , Naderian Mohammadreza , Limdi Nita , Irvin Marguerite R. , Tiwari Hemant , Mohan Sumit , Rao Maya , Dube Geoffrey , Chaudhary Ninad S. , Gutiérrez Orlando M. , Judd Suzanne E. , Cushman Mary , Lange Leslie A. , Lange Ethan M. , Bivona Daniel L. , Verbitsky Miguel , Winkler Cheryl A. , Kopp Jeffrey B. , Santoriello Dominick , Batal Ibrahim , Brant Pinheiro Sérgio Veloso , Araújo Oliveira Eduardo , e Silva Ana Cristina Simoes , Pisani Isabella , Fiaccadori Enrico , Lin Fangming , Gesualdo Loreto , Amoroso Antonio , Ghiggeri Gian Marco , D’Agati Vivette D. , Magistroni Riccardo , Kenny Eimear E. , Loos Ruth J.F. , Montini Giovanni , Hildebrandt Friedhelm , Paul Dirk S. , Petrovski Slavé , Goldstein David B. , Kretzler Matthias , Gbadegesin Rasheed , Gharavi Ali G. , Kiryluk Krzysztof , Sampson Matthew G. , Pollak Martin R. , Sanna-Cherchi Simone
Published: August 2023

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in theAPOL1gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Here, we show that the presence of theAPOL1p.N264K missense variant, when co-inherited with the G2APOL1risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of theAPOL1high-risk alleles. These findings have important implications for our understanding of the mechanisms ofAPOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
The Lancet peer reviewers and the COVID-19 pandemic
Authors: Masukume Gwinyai , Grech Victor
Published: August 2023

Introduction

Peer review is paramount to the scholarly article paradigm, helping to ensure the integrity and credibility of research.The Lancetplayed a crucial role in disseminating key information on the COVID-19 pandemic, publishing early clinical descriptions, risk factors for death, and effectiveness of measures like physical distancing and masks. Notably,The Lancetwas the world’s most cited journal for COVID-19 research, emphasising its significant impact on disseminating critical findings during the pandemic.

Methods

Geographic data forThe Lancet’speer reviewers in 2019 (pre-pandemic) and 2020 (pandemic) were analysed at the country level, ranking reviewer countries. A test of proportions compared reviewer numbers between the years.

Results

In 2020, China emerged as one of the top ten reviewer countries for the first time, with a significant increase from 1% (25 of 1843) in 2019 to 3% (54 of 1850), p=0.001. Italy also entered the top five reviewer countries, rising from 4% (67) to 5% (90), p=0.065. Reviewers from Africa 43 (2%) and South America 31 (2%) represented their continents in 2020. The top ten reviewer nations forThe Lancetin 2020 largely mirrored the top ten countries in global COVID-19 research output.

Conclusion

During the COVID-19 pandemic’s acute phase in 2020,The Lancet, the world’s most cited journal for COVID-19 research, featured peer reviewers who were largely representative of global COVID-19 research output. Notably, reviewers from China, the first country affected by COVID-19, increased significantly. However, underrepresentation of some continents persisted. To foster global idea exchange and enhance pandemic preparedness, research capacity worldwide must expand, broadening the reviewer pool—a vital step given uncertainties in future pandemic geographic origin.
Benchmarking clinical risk prediction algorithms with ensemble machine learning: An illustration of the superlearner algorithm for the non-invasive diagnosis of liver fibrosis in non-alcoholic fatty liver disease
Authors: Charu Vivek , Liang Jane W. , Mannalithara Ajitha , Kwong Allison , Tian Lu , Kim W. Ray
Published: August 2023

Background and Aims

Ensemble machine learning (ML) methods can combine many individual models into a single ‘super’ model using an optimal weighted combination. Here we demonstrate how an underutilized ensemble model, the superlearner, can be used as a benchmark for model performance in clinical risk prediction. We illustrate this by implementing a superlearner to predict liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

Methods

We trained a superlearner based on 23 demographic and clinical variables, with the goal of predicting stage 2 or higher liver fibrosis. The superlearner was trained on data from the Non-alcoholic steatohepatitis – clinical research network observational study (NASH-CRN, n=648), and validated using data from participants in a randomized trial for NASH (‘FLINT’ trial, n=270) and data from examinees with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES, n=1244). We compared the performance of the superlearner with existing models, including FIB-4, NFS, Forns, APRI, BARD and SAFE.

Results

In the FLINT and NHANES validation sets, the superlearner (derived from 12 base models) discriminates patients with significant fibrosis from those without well, with AUCs of 0.79 (95% CI: 0.73-0.84) and 0.74 (95% CI: 0.68-0.79). Among the existing scores considered, the SAFE score performed similarly to the superlearner, and the superlearner and SAFE scores outperformed FIB-4, APRI, Forns, and BARD scores in the validation datasets. A superlearner model derived from 12 base models performed as well as one derived from 90 base models.

Conclusions

The superlearner, thought of as the “best-in-class” ML prediction, performed better than most existing models commonly used in practice in detecting fibrotic NASH. The superlearner can be used to benchmark the performance of conventional clinical risk prediction models.