bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates of Positive M-CHAT-R Screenings by Pandemic Birth and Prenatal SARS-CoV-2 Exposure
Authors: Firestein Morgan R. , Manessis Angela Gigliotti , Warmingham Jen , Hu Yunzhe , Finkel Morgan A. , Kyle Margaret , Hussain Maha , Ahmed Imaal , Lavallée Andréane , Solis Ana , Chaves Vitoria , Rodriguez Cynthia , Goldman Sylvie , Muhle Rebecca A. , Lee Seonjoo , Austin Judy , Silver Wendy G. , O’Reilly Kally C. , Bain Jennifer M. , Penn Anna A. , Veenstra-VanderWeele Jeremy , Stockwell Melissa S. , Fifer William P. , Marsh Rachel , Monk Catherine , Shuffrey Lauren C. , Dumitriu Dani
Published: December 2024

Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68,p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37,p=0.29).These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.
Examining the association between theFTOgene and neuroticism reveals indirect effects on subjective well-being and problematic alcohol use
Authors: Cai Wenjie , Forsell Yvonne , Lavebratt Catharina , Melas Philippe A.
Published: December 2024

Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linkedFTOto addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study (PheWAS) across 4,756 genome-wide association studies (GWASs), identifying 26 psychiatric traits associated withFTOat the multiple-corrected significance level. These traits clustered into four categories: substance use, chronotype/sleep, well-being, and neuroticism. To validate these findings, we analyzed a functionally suggestiveFTOvariant (rs1421085) in a separate cohort, examining its impact on (i) alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), (ii) subjective well-being based on the WHO (Ten) Well-Being Index, and (iii) neuroticism based on Schafer’s Five Factor Model (FFM) or the Karolinska Scales of Personality (KSP). Our results confirmed a direct association between rs1421085 and neuroticism that was independent of age, sex, alcohol use, body mass index (BMI), and childhood adversities. Interestingly, while no direct association with alcohol intake was observed, both cross-sectional and lagged longitudinal mediation analyses uncovered indirect relationships between rs1421085 and problematic alcohol use (AUDIT-P), with increased neuroticism acting as the intermediary. Mediation analyses also supported an indirect effect of rs1421085 on lower well-being through the pathways of increased neuroticism and BMI. Our study is the first to validate a direct association betweenFTOand neuroticism. However, additional studies are warranted to affirm the causal pathways linkingFTOto well-being and alcohol use through neuroticism.
Long-term conditions in minoritised urban populations: Latin American community of London
Authors: Scuffell James , Bailey James , Dodhia Hiten , Durbaba Stevo , Ashworth Mark
Published: December 2024

Background

Minoritised populations in the United Kingdom frequently identify in multiple ethnic groupings and therefore little is known of their health needs. There were 136,062 Latin American people recorded in the 2021 UK Census across six different ethnic groups.

Aim

Characterise the incidence of long-term conditions (LTCs) and multiple LTCs (mLTCs) amongst the Latin American community of London.

Design and setting

Retrospective cohort study using pseudonymised primary care data from 890,922 individuals in an urban, superdiverse area of London from 2005-2022.

Method

Latin American individuals were identified using country of birth, language and ethnicity codes, and validated against Census findings. Multivariable competing risks regression models estimated the effect of being Latin American, compared to the White British ethnic group, on incidence of 32 LTCs and risk factors relevant to urban populations.

Results

28,617 Latin American people were identified in this cohort, 3.2% of total. In multivariable analysis, compared to the White British ethnic group, being Latin American was associated with twice the rate of HIV/AIDS (hazard ratio (HR) 2.00; 95% confidence interval (CI) 1.65–2.43), 60% increased rate of diabetes (HR 1.61; 95%CI 1.47–1.77) and almost twice the rate of systemic lupus erythematosus and rheumatoid arthritis (HRs 2.28; 95% CI 1.18–4.38 and 1.69; 95% CI 1.32–2.17 respectively).

Conclusion

Using commonly-recorded primary care codes accurately and reliably identifies markedly higher risks of HIV/AIDS, diabetes and joint disease among London’s Latin American population. These data can be used to target inclusive and equitable health interventions.

How it fits in

Little is known of the health of the United Kingdom’s (UK) Latin American population, who usually identify in multiple ethnic groups and are therefore hidden from ethnicity statistics. This study identified 28,617 Latin Americans using country of birth, ethnicity and language codes in a large primary care record dataset in London (n=890,438). Compared to the White ethnic group, the Latin American population are at higher risk of HIV/AIDS, diabetes, systemic lupus erythematosus and rheumatoid arthritis. These data reveal health inequalities in a frequently hidden and locally important population of the UK.
Automated Derivation of Diagnostic Criteria for Lung Cancer using Natural Language Processing on Electronic Health Records: A pilot study
Authors: Houston Andrew , Williams Sophie , Ricketts William , Gutteridge Charles , Tackaberry Chris , Conibear John
Published: December 2024

Background

The digitisation of healthcare records has generated vast amounts of unstructured data, presenting opportunities for improvements in disease diagnosis when clinical coding falls short, such as in the recording of patient symptoms. This study presents an approach using natural language processing to extract clinical concepts from free-text which are used to automatically form diagnostic criteria for lung cancer from unstructured secondary-care data.

Methods

Patients aged 40 and above who underwent a chest x-ray (CXR) between 2016-2022 were included. ICD-10 and unstructured data were pulled from their electronic health records (EHRs) over the preceding 12 months to the CXR. The unstructured data were processed using named entity recognition to extract symptoms, which were mapped to SNOMED-CT codes. Subsumption of features up the SNOMED-CT hierarchy was used to mitigate against sparse features and a frequency-based criteria, combined with univariate logarithmic probabilities, was applied to select candidate features to take forward to the model development phase. A genetic algorithm was employed to identify the most discriminating features to form the diagnostic criteria.

Results

75002 patients were included, with 1012 lung cancer diagnoses made within 12 months of the CXR. The best-performing model achieved an AUROC of 0.72. Results showed that an existing ‘disorder of the lung’, such as pneumonia, and a ‘cough’ increased the probability of a lung cancer diagnosis. ‘Anomalies of great vessel’, ‘disorder of the retroperitoneal compartment’ and ‘context-dependent findings’, such as pain, statistically reduced the risk of lung cancer, making other diagnoses more likely. The performance of the developed model was compared to the existing cancer risk scores, demonstrating superior performance.

Conclusions

The proposed methods demonstrated success in leveraging unstructured secondary-care data to derive diagnostic criteria for lung cancer, outperforming existing risk tools. These advancements show potential for enhancing patient care and results. However, it is essential to tackle specific limitations by integrating primary care data to ensure a more thorough and unbiased development of diagnostic criteria. Moreover, the study highlights the importance of contextualising SNOMED-CT concepts into meaningful terminology that resonates with clinicians, facilitating a clearer and more tangible understanding of the criteria applied.
Mapping ODI onto EQ-5D-5L in Chinese Low Back Pain Patients
Authors: Li Jia , Du Shuzhang , Chen Chengqun , Ye Ziping
Published: December 2024

Mapping can translate utility values from other health-related quality-of-life scales, giving researchers and policymakers more comprehensive information. The primary objective of the study is to develop mapping algorithms that convert scores from the Oswestry Disability Index (ODI) to the 5-level EuroQol-5 Dimension (EQ-5D-5L). Data for this analysis was sourced from 272 patients suffering from low back pain. The development of the mapping algorithms involved the application of three distinct regression methods across four different settings: ordinary least squares regression, beta regression, and multivariate ordered probit regression. To evaluate the internal validity of these algorithms, we adopted a ‘hold-out’ approach for predictive performance assessment. Furthermore, to discern the most effective model, three goodness-of-fit tests were employed: the mean absolute error (MAE), the root-mean-square error (RMSE), and the Spearman rank correlation coefficients between the predicted and observed utilities. The study successfully developed several models capable of accurately predicting health utilities in the specified context. The best performing models for ODI to EQ-5D-5L mapping were beta regressions. Mapping algorithms developed in this study enable the estimation of utility values from the ODI. The algorithms formulated in this study facilitate the estimation of utility values based on the ODI, providing a valuable empirical foundation for estimating health utilities in scenarios where EQ-5D data is unavailable.
Epidemiological description and analysis of factors associated with cholera morbidity and mortality in Cameroon from 2018 to 2023
Authors: Mboringong Akenji Blaise , Ngomtcho Sen Claudine , Armel Evouna , Linda Esso , Luc Dibog , Patricia Mendjime , Sandrine Belinga , Flore Balana , Ntamack Theodore , Mballa Etoundi , Ndip Roland
Published: December 2024

Introduction

Cameroon has faced frequent and severe cholera outbreaks since 1971, with high lethality. Previous studies have examined some risk factors and groups, but not for the 2018–2023 period. We analysed the profiles of cholera epidemics and determined factors associated with morbidity and mortality from cholera during this period.

Materials and methods

We conducted an analytical cross-sectional study using Ministry of Health cholera databases from 2018–2023. We described the socio-demographic, clinical and geographical distribution of cholera cases and used multiple regression to identify factors associated with cholera lethality.

Results

Between May 2018 and March 2023, there were four cholera epidemics with 18,986 cases, affecting 8/10 regions. The three coastal regions notified 83.4% (15,839/18,986) of cases. The most represented age group were those aged 25–35 years (21.9%; 4,163/1,876) and the M/F sex ratio was 1.27. The overall CFR was 2.7% (478 deaths/17,967 cases) and was highest among persons >65 years (6.8%; 59/869). Urban areas notified more cases than rural areas (13,267 vs 5,484). Factors associated with increased mortality were female sex (aOR 0.62, 95% CI 0.49-0.77), rainy season (aOR 0.60, 95% CI 0.45-0.78) and age below 45 years (aOR 0.56, 95% CI 0.45-0.69). Severe dehydration at consultation (aOR 12.76, 95% CI 7.66-21.25) was associated with higher mortality.

Conclusion

There were frequent cholera epidemics affecting nearly all administrative regions in Cameroon from 2018 to 2023. Factors associated with decreased mortality from cholera were female sex, living in urban areas, the rainy season, and age less than 45 years. The high caseloads and case fatality rates further reiterate the need for a multisectoral approach to the fight against cholera in Cameroon.
Disparities in ABO Blood Type Determination Across Diverse Ancestries: A Systematic Review and Validation in theAll of UsResearch Program
Authors: Martinez Kiana L. , Klein Andrew , Martin Jennifer R. , Sampson Chinwuwanuju U. , Giles Jason B. , Beck Madison L. , Bhakta Krupa , Quatraro Gino , Farol Juvie , Karnes Jason H.
Published: December 2024

Background

ABO blood types have widespread clinical use and robust associations with cardiovascular disease. Many studies determine ABO blood types using tag single nucleotide polymorphisms (tSNPs) to characterize functional variation. However, tSNPs with low linkage disequilibrium (LD) may promote misinference of ABO blood types, particularly in diverse populations.

Methods

Bibliographic databases were searched for studies (2005-2022) using tSNPs to determine ABO alleles in accordance with PRISMA 2020 guidelines. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes (AFR, AMR, EAS, EUR). We compared r2across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a large, diverse population from theAll of UsResearch Program (AoURP).

Results

We observe a lack of phasing and frequent use of inappropriate tSNPs in blood type determination, particularly for O alleles. Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2=0.443) compared to East Asian (r2=0.946, p=1.1×10-5) and European (r2=0.869, p=0.023). In AoURP, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ=-0.90, p=3.08×10-23).

Conclusion

We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals. Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations.
Safety and efficacy of the Plasma Directed Electron Beam (PDEB™) - implications for enhanced wound healing treatment in military operational medicine and beyond
Authors: Bauer Joseph A. , Blocklin Adrianne R. , Sysel Annette M. , Sheperak Thomas J.
Published: December 2024

Introduction

Wound healing presents a critical challenge in military operational medicine and combat casualty care, especially for soldiers in high-risk environments such as combat zones and training exercises. In these scenarios, wounds often result from bullets, shrapnel, burns, and blasts, affecting soft tissue, bone, and internal organs, and are frequently contaminated with hazardous substances like debris and bacteria. Limited resources in these environments make rapid and effective treatment difficult, often leading to delayed medical care and poorer healing outcomes. Emerging technologies like nonthermal plasma (NTP), also known as cold plasma, may provide superior wound healing treatment efficacy in these environments, owing to the ability to effectively kill pathogens, stimulate tissue regeneration, and minimize collateral damage compared to traditional methods. The Plasma Directed Electron Beam™ (PDEB™), an innovative advancement in nonthermal plasma research, shows promise in addressing these challenges.

Materials and Methods

The antibiofilm efficacy of the PDEB™ was investigated on Acinetobacter baumannii and Streptococcus mutans. Cytotoxicity was assessed using primary human epithelial cells and TR146 cells, immortalized epithelial cells. Cell proliferation assays, immunoblotting, and lactate dehydrogenase (LDH) release were evaluated.

Results

Our study demonstrates the effectiveness of the PDEB™ handheld in inhibiting the growth of bacterial pathogens implicated in biofilms. Acinetobacter baumannii and Streptococcus mutans showed zones of inhibition starting at lower power levels, achieving complete inhibition at 14 watts (W) and 7W respectively for 90-120 seconds. The safety of the PDEB™ was assessed through cell proliferation assays using human epithelial cells and semi-confluent TR146 cells, which were exposed to similar conditions as the bacterial assays. TR146 cells showed negligible differences in cleaved caspase 3 levels compared to controls. Cytotoxicity and apoptosis assays further confirmed the safety of PDEB™, as lactate dehydrogenase (LDH) release in epithelial cells and activated caspase 3 levels in cell extracts were comparable to untreated and helium-treated cells, indicating minimal cellular damage.

Conclusion

The PDEB™ handheld, a first-generation device, has demonstrated significant efficacy in inhibiting the growth of bacteria. Concurrently, its application on human epithelial cells has shown encouraging safety profiles. These findings align with the effectiveness of traditional nonthermal plasma devices, positioning the PDEB™ as a viable and promising option for wound healing applications in Combat Casualty Care and Military Operational Medicine.
A co-produced community engagement workshop in South London to reduce psychosis related stigma
Authors: Cai Shujun , Koroma Joelyn N’Danga , Graham Charlotte , McKay Meagan , Bray Caroleen , Colgan Lauren , Lynch Sarah , Fitzell Sharon , Akande Isaac , Spencer Thomas J
Published: December 2024

Background

Early access to services is essential for those suffering a psychotic illness or at risk for the condition. Lack of knowledge of services and public stigma are major barriers to care and are associated with increased duration of untreated psychosis and delays in those at clinical high-risk for psychosis (CHR-P) from accessing support. Education and contact programmes have shown promise in reducing stigmatizing views, however, few have been co-produced and delivered by service users and clinical staff. A three-hour co-produced educational workshop was developed and delivered by service users and Outreach and Support in South London (OASIS) staff. The aim was to assess the feasibility of delivering a co-produced workshop to youth community workers, to see if it improved knowledge of psychosis, attitudes to mental health services and reduced stigma towards people with psychosis as well as seeing if the workshop increased community referrals to OASIS.

Method

Educational workshops were developed by community stakeholders and service users. Pre- and post-workshop questionnaires assessed knowledge of psychosis, attitudes towards mental health teams and stigma towards individuals with a psychotic disorder. Participants’ and service users’ views on the workshop were explored through two focus groups.

Results

9 workshops were delivered to 75 community participants. Following the workshop participants’ questionnaire scores showed improvements in knowledge of psychosis, improved attitudes towards mental health teams and a reduction in stigmatizing views towards people with psychosis. The workshop was overwhelmingly well received with 97% agreeing with the statement that they learnt something valuable from the workshop. Referrals to the OASIS service increased by 22% following the workshops.

Conclusion

The co-produced educational workshop designed and delivered by service users and OASIS staff was successful in improving participants’ knowledge, attitudes and reducing stigma. We observed an increase in the rate of referrals to the OASIS service, although it is difficult to whether this was due to the workshops or to other outreach activities. Future research should examine whether these effects are long-lasting and explore online delivered workshops to reach more participants in the wider community.
Evaluation value of bedside ultrasound monitoring of peak flow velocity of abdominal aorta and its branches in volume status of patients with septic shock
Authors: Wenchong Chen , Weixin Guo , Xiaodan Zeng , Deping Li , Jianli Luo , Yafeng Zhou , Sicheng Zhao , Pinghui Lu
Published: December 2024

Objective

To explore the value of bedside ultrasound in monitoring peak flow velocity of abdominal aorta and its branches in assessing the volume status of patients with septic shock.

Methods

A total of 80 patients with septic shock admitted to the Foshan Rehabilitation Hospital(The Fifth People’s Hospital of Foshan) and the Guangdong Provincial People’s Hospital from June 2022 to June 2023 were selected as the research subjects. All patients were treated with mechanical ventilation,and deep venous catheters were placed in the internal jugular vein or subclavian vein to monitor central venous pressure (CVP).PiCCO catheters were placed in the femoral artery to monitor hemodynamic data.At the same time,the maximum internal diameter of the inferior vena cava (IVCmax),the respiratory variation of the inferior vena cava (□IVC),the peak flow velocity of the abdominal aorta (VpeakAA),the peak flow velocity of the celiac artery (VpeakCA),and the peak flow velocity of the superior mesenteric artery (VpeakSMA)were monitored under bedside ultrasound.The global end-diastolic volumn index(GEDI)was used as a grouping indicator,with GEDI≤680ml/m2 as the low-volume group and GEDI≥800ml/m2 as the high-volume group.Compare the differences in peak flow velocity between the abdominal aorta,celiac artery,and superior mesenteric artery between the two groups,and analyze the correlation between peak flow velocity of the abdominal aorta,celiac artery,and superior mesenteric artery and IVCmax,ΔIVC,CVP,and stroke volume variability (SVV);draw a receiver operating characteristic (ROC) curve for the subjects,calculate the area under the curve,and find the diagnostic threshold.

Results

There was no significant difference in general data between the two groups (P>0.05).The VpeakAA,VpeakCA,and VpeakSMA in the high-volume group were all higher than those in the low-volume group, and the differences were statistically significant (P<0.05). However,VpeakCA and VpeakSMA were significantly correlated with IVCmax, △ IVC,CVP,and SVV (P<0.05).The ROC curve analysis showed that VpeakAA,VpeakCA,and VpeakSMA could effectively evaluate the volume status of patients with septic shock, and the area under the VpeakSMA curve was 0.846,with a 95% confidence interval of 0.693-0.999,and had high sensitivity and specificity.

Conclusion

Bedside ultrasound can dynamically monitor VpeakAA,VpeakCA,and VpeakSMA,which has great value in the evaluation of volume status in patients with septic shock.
Ursodeoxycholic acid for trans intestinal cholesterol excretion stimulation: a randomized placebo controlled cross-over study
Authors: Oostveen R.F. , Kaiser Y. , Hartgers M.L. , Meessen E.C.E. , Grefhorst A. , Hovingh G.K. , Kuipers F. , Stroes E.S.G. , Groen A.K. , Reeskamp L.F.
Published: December 2024

Objective

The Trans Intestinal Cholesterol Excretion (TICE) pathway is a potential therapeutic target to reduce plasma low-density lipoprotein (LDL) cholesterol levels. TICE encompasses the direct excretion of cholesterol by enterocytes into feces. In mice TICE has been shown to be stimulated by a hydrophilic bile acid pool, resulting in increased fecal neutral sterols (FNS) loss and reduced plasma cholesterol levels. We investigated whether treatment with a hydrophilic bile acid – ursodeoxycholic acid (UDCA) - would increase FNS in humans as a proxy for TICE.

Approach and results

We performed a randomized double-blind placebo controlled cross-over trial in 20 male participants aged >18 years, with plasma LDL cholesterol levels ≥2.6mmol/L. After a run-in period of ezetimibe 20mg once daily for three weeks, patients were randomized to UDCA 600mg or placebo orally once daily for two weeks. After a three week wash-out, patients underwent the alternate treatment.

At baseline, mean (SD) age, BMI, and plasma LDL cholesterol were 59±11.3 years, 26.4±3.1 kg/m2, and 3.9±0.8 mmol/L, respectively. After UDCA treatment, the plasma bile acid hydrophobicity index was reduced compared to placebo (-115.88% versus +1.85%, p<0.001). The FNS did not change (-5.8% versus +18.8%, p=0.51) and treatment with UDCA increased LDL cholesterol with 0.39 mmol/L (+10.95% versus -3.24%, p=0.002) when compared with placebo.

Conclusion

UDCA in combination with ezetimibe increased plasma bile acid hydrophilicity in hypercholesterolaemic subjects, but did not result in increased FNS or decreased LDL cholesterol. This suggests that TICE is not stimulated by an increase in the hydrophilicity of the bile acid pool in humans.
Blood lead levels and bladder cancer among US participants: NHANES 1999–2018
Authors: Huang Mei , Li Hongxiao , Chen Jiahui , Li Liuqiang , Zhan Yifei , Bian Jun , Chen Meiling , Lai Dehui
Published: December 2024

Background

Lead is a toxic metal for human health, but its carcinogenicity is controversial, and the effect on bladder cancer is still unknown. The object of this study was to demonstrate the link between blood lead and bladder cancer.

Objectives

We investigated associations of lead exposures with bladder cancer.

Methods

We used the database from the National Health and Nutrition Examination Survey (NHANES, 1999–2018) to perform a cross-sectional study. We performed Weighted multivariate logistic regression to examine the association between blood lead level with bladder cancer, and then a subgroup analysis was performed. The nonlinear association between BLL and bladder cancer was described using fitted smoothing curves.

Results

A total of 40,486 participants were included in this study, the mean (SD) BMI was 28.71 ± 6.68 kg/m2. A fully adjusted model showed that BLL was parallel associated with bladder cancer (Odds ratio [OR] = 2.946, 95% Confidence interval [CI] = 1.025 to 8.465, P = 0.047) in people with BMI < 28kg/m2. However, no difference was found in BMI≥28kg/m2 subgroup and in General population. In subgroup analysis of participants with BMI < 28kg/m2, blood lead was associated with bladder cancer in the male, non-hypertensive, < 70 year old subgroup (p< 0.05), but was not significantly different from the other subgroups. Additionally, we discovered a non-linear association between BLL and bladder cancer using a linear regression model.

Discussion

In this cross-sectional study, we identified higher BLL level was independently associated with Bladder cancer in People with BMI<28kg/m2.The results compensated for earlier investigations, but more large-scale prospective cohorts were required for validation.
18F-NaF Uptake on Vascular PET Imaging in Symptomatic versus Asymptomatic Atherosclerotic Disease: a Meta-Analysis
Authors: Bhakta S , Chowdhury MM , Tarkin JM , Rudd JHF , Warburton EA , Evans NR
Published: December 2024

Introduction

18F-sodium fluoride (NaF) positron-emission tomography (PET) is increasingly being used to measure microcalcification in atherosclerotic diseasein vivo. Correlations have been drawn between sodium fluoride uptake and the presence of high-risk plaque features, as well as its association with clinical atherosclerotic sequelae. The aim of this review was to perform a meta-analysis of NaF uptake on PET imaging and its relation to symptomatic and asymptomatic disease.

Methods

A systematic review was performed according to PRISMA guidelines, via searching the MEDLINE database up to August 2023. The search strategy included the terms “NaF”, “PET” and “plaque”, and all studies were included where there was data listed regarding the degree of microcalcification, as measured by18F-NaF uptake in symptomatic and asymptomatic atherosclerotic plaques. Analysis involved calculating standardized mean differences between uptake values and comparison using a random-effects model.

Results

A total of 15 articles, involving 423 participants, were included in the meta-analysis. Comparing18F-NaF uptake in symptomatic vs asymptomatic atherosclerotic plaques, a standardized mean difference of 0.42 (95% CI 0.29-0.56; p<0.001, I2= 54.1%) was noted for those studies comparing symptomatic and asymptomatic plaques in the same participant, with no significant change in effect based on arterial territory studied (QM= 5.02, p = 0.08). In those studies where data was included from participants with and without symptomatic disease, the standardized mean difference between symptomatic and asymptomatic plaques was 0.44 (95% CI 0.03-0.85, p=0.037, I2= 40.4%). All studies including asymptomatic participants were investigating carotid disease.

Conclusions

PET imaging using18F-NaF can detect differences in microcalcification between symptomatic and asymptomatic atherosclerotic plaques within and between individuals, and is a marker of symptomatic disease. The standardization of18F-NaF PET imaging protocols, and its future use as a risk stratification tool or outcome measure, requires further study.
Middle meningeal artery embolization for subdural hematoma: protocol for a systematic review and meta-analysis of randomized controlled trials
Authors: Wang Alick P , Shakil Husain , Drake Brian J
Published: December 2024

Background

Middle meningeal artery embolization is an emerging neuroendovascular therapy for chronic subdural hematoma. Recently, a number of randomized control trials have been conducted to assess the efficacy of middle meningeal artery embolization to reduce the recurrence or progression of chronic subdural hematoma.

Methods

A systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The authors will systematically search MEDLINE, EMBASE, Cochrane, andClinicalTrials.gov(National Library of Medicine) for randomized control trials evaluating middle meningeal artery embolization for chronic subdural hematoma. A meta-analysis will be undertaken to compare patients undergoing middle meningeal artery embolization and standard care compared to standard care alone; primary effectiveness endpoints will be symptomatic recurrence, radiographic re-accumulation, or reoperation; secondary safety endpoints will be new disabling stroke, myocardial infarction, or death within 30 days.

Discussion

This proposed systematic review and meta-analysis will synthesize and appraise available data regarding middle meningeal artery embolization, a novel neurointerventional therapy. Findings will help clinicians, patients, administrators, policy makers to determine the role of this new treatment and its potential benefits.

Systematic review registration

PROSPERO #CRD42024512049
Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis
Authors: Vardavas Constantine I. , Nikitara Katerina , Mathioudakis Alexander G. , Delialis Dimitris , Marou Valia , Ramesh Nithya , Stamatelopoulos Kimon , Georgiopoulos Georgios , Phalkey Revati , Leonardi-Bee Jo , Deogan Charlotte , Lamb Favelle , Mougkou Aikaterini , Pharris Anastasia , Suk Jonathan E.
Published: December 2024

Background

There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity.

Methods

A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects.

Findings

Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated.

Interpretation

Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed.
What support is needed for preconception health improvement, and by whom? A qualitative study of women’s views
Authors: Daly Michael P , Kipping Ruth R , White James , Sanders Julia
Published: December 2024

Background

Systematic reviews suggest preconception health interventions may be effective in improving maternal and infant outcomes. However, few studies have explored women’s views on the types of support required for preconception health improvement, nor when and to whom this support should be provided.

Methods

We purposively sampled women aged 18-48 years in the West of England from respondents to a survey, and conducted semi-structured in-depth interviews to explore their views on support needs in the preconception period and target populations for this support. We analyzed the data using a data-driven framework analysis.

Results

The women we interviewed (N=20) broadly supported promoting greater awareness of preconception health and felt the limited focus on health before pregnancy downplays its importance relative to antenatal health. Some women opposed support services and structural interventions to improve preconception health, due to concerns these are less impactful than encouraging individual responsibility for health. Women who supported structural interventions highlighted broader determinants of health and socioeconomic barriers to preconception health improvement. Men were considered a key target population for preconception support, to help share the burden for preconception health improvement. Women broadly supported ‘age-appropriate’, school-based preconception health education, highlighting young women as an under-served group in need of additional preconception education.

Conclusion

Our findings indicate a need to deliver early preventive support ahead of first pregnancy through services, interventions and policies co-produced with women and women’s partners. Future research should explore how to increase public understanding of the socioeconomic, environmental and commercial determinants of preconception health.

HIGHLIGHTS

Women broadly supported promoting greater awareness of preconception health

Neoliberal views on responsibility underlay opposition to structural interventions

Awareness of wider health determinants underlay support for structural interventions

Suggested support included preconception health checks and community support groups

Young women were considered an under-served group in terms of preconception support
Understanding Healthcare Barriers for Latino/a/e/x Families with Alzheimer’s Disease: Insights from Primary Care Provider interviews
Authors: Garcia Diana Martinez , Pinzon Maria Mora , Perales-Puchalt Jaime
Published: December 2024

Background

Alzheimer’s Disease and Related dementias (ADRD) are disproportionately underdiagnosed, misdiagnosed, and undertreated in Latino/a/e/x populations living in the U.S. Latino/a/e/x families also experience low access to ADRD caregiver support services and high levels of depression. Primary care providers (PCPs) are the first point of contact for patients and their families, and they are critical in understanding the factors associated with disparities in accessing services. This project aims to reflect on the barriers that Latino/a/e/x families experience in accessing and using healthcare services from the perspective of PCPs.

Methods

The data was collected through structured interviews with 23 diverse PCPs across the US via videoconference or phone calls. Participants were recruited via snowball sampling. Two reviewers used an inductive coding approach to conduct qualitative thematic analysis. The Rigorous and Accelerated Data Reduction (RADaR) technique was used to extract relevant data and organize it into relevant categories.

Results

Some of the themes identified reflect the experiences of individuals in the diagnostic process and subsequent care: 1) Family members are usually the first ones to notice the symptoms, 2) Delays in seeking care might be partially influenced by denial from individuals and their families, 3) Language congruency promotes the disclosure of symptoms, 4) Care that is linguistically and literacy appropriate requires additional support of patients and families, and 5) Caregiving expectations and preferences by Latino/a/e/x families do not shield caregivers from feeling burnout. Overall, PCPs reflected that the experiences of individuals are highly influenced by socioeconomic factors, which also influence their care plans.

Conclusion

Most Latino/a/e/x older adults with ADRD will be cared for by a PCP at some point during their disease, which means that they require additional support and resources at primary care appointments to address the barriers to accessing care services and enhance health equity in Latino/a/e/x communities.
tet2 and tet3 regulate cell fate specification and differentiation events during retinal development
Authors: Heilman Shea A , Schriever Hannah C , Kostka Dennis , Koenig Kristen M , Gross Jeffrey M
Published: December 2024

Abstract

Tet enzymes are epigenetic modifiers that impact gene expression via 5mC to 5hmC oxidation. Previous work demonstrated the requirement for Tet and 5hmC during zebrafish retinogenesis.tet2-/-;tet3-/-mutants possessed defects in the formation of differentiated retinal neurons, but the mechanisms underlying these defects are unknown. Here, we leveraged scRNAseq technologies to better understand cell type-specific deficits and molecular signatures underlying thetet2-/-;tet3-/-retinal phenotype. Our results identified defects in thetet2-/-;tet3-/-retinae that included delayed specification of several retinal cell types, reduced maturity across late-stage cones, expansions of immature subpopulations of horizontal and bipolar cells, and altered biases of bipolar cell subtype fates at late differentiation stages. Together, these data highlight the critical role that tet2 and tet3 play as regulators of cell fate specification and terminal differentiation events during retinal development.
Reduced and Redundant: Information Processing of Prediction Errors during Sleep
Authors: Blume Christine , Dauphin Marina , Niedernhuber Maria , Spitschan Manuel , Meyer Martin P. , Cajochen Christian , Bekinschtein Tristan , Canales-Johnson Andrés
Published: December 2024

During sleep, the human brain transitions to a ‘sentinel processing mode’, enabling the continued processing of environmental stimuli despite the absence of consciousness. Going beyond prior research, we employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy.

To investigate this, twenty-nine young healthy participants were exposed to an auditory ‘local-global’ oddball paradigm during wakefulness and continued during an 8-hour sleep opportunity monitored via polysomnography. We focused on ‘local’ mismatch responses to a deviating fifth tone following four standard tones.

ERP analyses showed that prediction error processing continued throughout all sleep stages (N1-N3, REM). Mutual information analyses revealed a substantial reduction in the amount of encoded prediction error information during sleep, although ERP amplitudes increased with deeper NREM sleep. In addition, co-information analyses showed that neural dynamics became increasingly redundant with increasing sleep depth. Temporal generalisation analyses revealed a largely shared neural code between N2 and N3 sleep, although it differed between wakefulness and sleep.

Here, we showed how the neural code of the ‘sentinel processing mode’ changes from wake to light to deep sleep and REM, characterised by more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information changes with the changes of consciousness states as we traverse the night.
Stimulus-repetition effects on macaque V1 and V4 microcircuits explain gamma-synchronization increase
Authors: Katsanevaki Christini , Bosman Conrado A. , Friston Karl J. , Fries Pascal
Published: December 2024

Under natural conditions, animals repeatedly encounter the same visual scenes, objects or patterns repeatedly. These repetitions constitute statistical regularities, which the brain captures in an internal model through learning. A signature of such learning in primate visual areas V1 and V4 is the gradual strengthening of gamma synchronization. We used a V1-V4 Dynamic Causal Model (DCM) to explain visually induced responses in early and late epochs from a sequence of several hundred grating presentations. The DCM reproduced the empirical increase in local and inter-areal gamma synchronization, revealing specific intrinsic connectivity effects that could explain the phenomenon. In a sensitivity analysis, the isolated modulation of several connection strengths induced increased gamma. Comparison of alternative models showed that empirical gamma increases are better explained by (1) repetition effects in both V1 and V4 intrinsic connectivity (alone or together with extrinsic) than in extrinsic connectivity alone, and (2) repetition effects on V1 and V4 population input rather than output gain. The best input gain model included effects in V1 granular and superficial excitatory populations and in V4 granular and deep excitatory populations. Our findings are consistent with gamma reflecting bottom-up signal precision, which increases with repetition and, therefore, with predictability and learning.

Highlights

We model learning effects in macaque visual cortex using Dynamic Causal Modeling.

Microcircuit-level changes explain the repetition-induced gamma increases.

The best models include changes 1) within V1 and V4 and 2) in neuronal input gain.

Gamma may reflect bottom-up signal precision.
Sensor Movement Drives Emergent Attention and Scalability in Active Neural Cellular Automata
Authors: Kvalsund Mia-Katrin , Ellefsen Kai Olav , Glette Kyrre , Pontes-Filho Sidney , Lepperød Mikkel Elle
Published: December 2024

The brain’s distributed architecture has inspired numerous artificial intelligence (AI) systems, particularly through its neocortical organization. However, current AI approaches largely over-look a crucial aspect of biological intelligence: active sensing – the deliberate movement of sensory organs to explore the environment. To explore how sensor movement impacts behavior in classification tasks, we introduce the Active Neural Cellular Automata (ANCA), a neocortex-inspired model with movable sensors. Active sensing naturally emerges in the ANCA, with belief-informed exploration and attentive behavior to salient information, without adding explicit attention mechanisms. Active sensing both simplifies classification tasks and leads to a highly scalable system. This enables ANCAs to be smaller than the image size without losing information and enables fault tolerance to damaged sensors. Overall, our work provides insight to how distributed architectures can interact with movement, opening new avenues for adaptive AI systems in embodied agents.
Space- and object-based attention in patients with a single hemisphere following childhood resection
Authors: Robert Sophia , Granovetter Michael C. , Ling Shouyu , Behrmann Marlene
Published: December 2024

The neural processes underlying attentional processing are typically lateralized in adults, with spatial attention associated with the right hemisphere (RH) and object-based attention with the left hemisphere (LH). Using a modified two-rectangle attention paradigm, we compared the lateralization profiles of individuals with childhood hemispherectomy (either LH or RH) and age-matched, typically developing controls. Although patients exhibited slower reaction times (RTs) compared to controls, both groups benefited from valid attentional cueing. However, patients experienced significantly higher costs for invalid trials—reflected by larger RT differences between validly and invalidly cued targets. This was true for invalid trials on both cued and uncued objects, probes of object- and space-based attentional processes, respectively. Notably, controls showed no significant RT cost differences between invalidly cued locations on cued versus uncued objects. By contrast, patients exhibited greater RT costs for targets on uncued versus cued objects, suggesting greater difficulty shifting attention across objects. We explore potential explanations for this group difference and the lack of difference between patients with LH or RH resection. These findings enhance our understanding of spatial and object-based attention in typical development and reveal how significant neural injury affects the development of attentional systems in the LH and RH.