bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: a repeated cross-sectional survey, 2021-2022
Authors: Heilmann Elizabeth , Tembo Tannia , Fwoloshi Sombo , Kabamba Bupe , Chilambe Felix , Kalenga Kalubi , Siwingwa Mpanji , Mulube Conceptor , Seffren Victoria , Bolton-Moore Carolyn , Simwanza John , Yingst Samuel , Yadav Ruchi , Rogier Eric , Auld Andrew F. , Agolory Simon , Kapina Muzala , Gutman Julie R. , Savory Theodora , Kangale Chabu , Mulenga Lloyd B. , Sikazwe Izukanji , Hines Jonas Z.
Published: January 2024

Background

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia.

Methods

We conducted repeated cross-sectional surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on COVID-19 vaccination status and anti-RBD and anti-nucleocapsid test results.

Findings

Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants.

Interpretation

Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.
Blood-brain barrier integrity decreases with higher blood pressure, a 7T DCE-MRI study
Authors: van den Kerkhof Marieke , de Jong Joost J.A. , Voorter Paulien H.M. , Postma Alida , Kroon Abraham A. , van Oostenbrugge Robert J. , Jansen Jacobus F.A. , Backes Walter H.
Published: January 2024

Background

Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension antedates various cerebrovascular diseases, such as cerebral small vessel disease (cSVD), and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this study, we investigated the relation between hypertension, current blood pressure and BBB leakage in human subjects.

Methods

BBB leakage was determined in twenty-two patients with hypertension and nineteen normotensive controls, age- and sex-matched (median age[range]:65[45-80] years,19 males), using a sparsely time-sampled contrast-enhanced 7 Tesla MRI protocol. Structural cSVD markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors and cSVD markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), drug treatment, and BBB leakage.

Results

Both hypertensive and normotensive participants showed mild scores of cSVD. BBB leakage did not differ between hypertensive and normotensive participants, however was significantly higher for SBP, DBP and MAP in the cortex, and DBP and MAP in the grey matter. Effectively treated patients showed less BBB leakage than those with current hypertension.

Conclusion

BBB integrity in the total and cortical grey matter decreases with increasing blood pressure, but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB.

Registered at:https://trialsearch.who.int/; Unique identifier: NL7537
Hypertension mediated the effects of pericardial adipose tissue on cardiovascular diseases
Authors: Xie Feng , Cao Peng , Tang Hai-bo , Luo Zhi , Zhu Shai-hong , Zhu Li-yong
Published: January 2024

Background

Although previous studies have presented a relevance between pericardial adipose tissue (PAT) and cardiovascular diseases (CVDs), the precise role of PAT in CVDs remains uncertain.

Methods

In the Mendelian randomization (MR) research, we extracted instrumental variants significantly correlated with PAT to assess its effects on CVDs. Inverse-variance weighted model was elected as the leading MR analytical method. F-statistic was utilized to assess the intensity of instrumental variants and avert weak-tool bias. Numerous sensitivity analyses were adopted to confirm the credibility of outcomes. The mediated effect of hypertension between PAT and CVDs was estimated in 2-step MR analysis.

Results

The MR research demonstrated genetically determined PAT was remarkably correlated with greater risks of cardiovascular disease (OR 1.15; 95% CI 1.09--1.22, P=1.32*10-6), heart failure (OR 2.62; 95% CI 1.28--5.34, P=0.008), coronary heart disease (OR 3.53; 95% CI 1.55--8.06, P=0.003), ischemic heart disease (OR 2.31; 95% CI 1.14--4.67, P=0.020), ischemic stroke (OR 3.18; 95% CI 1.63--6.20, P=0.001), and venous thromboembolism (OR 1.02; 95% CI 1.00--1.04, P=0.015). And the correlation was partially mediated by hypertension. Results were verified by sensitivity analysis.

Conclusions

Genetic determined PAT was remarkably correlated with additional risks of diverse CVDs. Identified as a mediator, hypertension had a significant influence on the causal association. The correlation between PAT and CVDs deserves further exploration.

NOVELTY AND RELEVANCE

What Is New?

This was the first Mendelian randomization research to detect the potential causal relationship of genetically determined PTA on multiple CVDs risks and confirm the mediating effect of hypertension on the causal association.

What Is Relevant?

The MR research not only estimated the causal effect of PAT on hypertension but also identified the mediating role of hypertension between PAT and CVDs.

Clinical/Pathophysiological Implications?

This study revealed PAT promoted CVDs progression and hypertension played an intermediary role, which indicated that PAT might serve as a potential therapeutic target and antihypertensive drugs could be conjunctly used to provide cardiovascular benefits.

especially for people with obesity, because they had more PAT accumulation.
Predicting Impaired Cerebrovascular Reactivity and Hyperperfusion Syndrome with BeamSAT MRI in Carotid Artery Stenosis
Authors: Ikeuchi Yusuke , Kohta Masaaki , Yamashita Shunsuke , Yamanishi Shunsuke , Yamaguchi Yoji , Tanaka Jun , Tanaka Kazuhiro , Kimura Hidehito , Fujita Atsushi , Hosoda Kohkichi , Kohmura Eiji , Sasayama Takashi
Published: January 2024

Background

We evaluated the impact of collateral flow of the middle cerebral artery (MCA) territory and cross flow visualized with internal carotid artery (ICA)-selective Magnetic resonance angiography (MRA) constructed by pencil beam presaturation (BeamSAT) pulse on preoperative cerebral hemodynamic status and postoperative hyperperfusion syndrome.

Methods

Fourty-eight patients who underwent carotid artery stenting or carotid endarterectomy were included. The preoperative status of collateral flow in the MCA territory and crossflow was assessed using ICA-selective MRA. Cerebral blood flow and cerebrovascular reactivity (CVR) were assessed using single-photon emission computed tomography. Potential signs of hyperperfusion syndrome (HPS) were retrospectively assessed by reviewing medical charts.

Results

Patients who either demonstrated mismatch in MCA signal intensity (MCA-MRA grade) between ICA-selective MRA by BeamSAT magnetic resonance imaging (MRI) and conventional MRA or whose MRA crossflow was visualized on BeamSAT MRI were placed in the developed collateral (DC) group (n=19). All other patients were placed in the undeveloped collateral (UC) group (n = 29). Preoperative ipsilateral CVR was significantly lower in the DC group than in the UC group (18.0±20.0% versus 48.3±19.5%; P<0.0001). Multivariate logistic regression analysis revealed that the DC group was significantly associated with impaired CVR (odds ratio [OR] = 17.7, [95%confidence interval [CI]: 1.82 to 171]; P = 0.013). The partial area under curves (AUCs) of BeamSAT logisitic model (0.843) were significantly larger than those of the conventional logistic model (0.626) over the range of high sensitivity (0.6-1) (p = 0.04). The incidence of postoperative symptoms suggestive of HPS was significantly higher in the DC group than in the UC group (8/19 vs. 1/29; P=0.001).

Conclusions

The differences in the MCA-MRA grade and crossflow between ICA-selective and conventional MRA were associated with impaired CVR. BeamSAT MRI may be a valuable and non-invasive tool for assessing of cerebral hemodynamics and predicting postoperative HPS.
Profiling health and socioeconomic disadvantage in the northern Adelaide Local Health Network population
Authors: Shoubridge Cheryl , Maddison John , Lynch John , Boyd Mark
Published: January 2024

Objective

This study aimed to describe and compare aspects of the socioeconomic and health status of the population within regions of an Australian capital city.

Design

This comparative study harnessed publicly available, deidentified, population level data from the 2021 census spanning measures of relative disadvantage, population demographics, health status and risk factors known to contribute to health outcomes. We describe data for greater Australian capital cities and compare aggregate public health area data that reflect local health network boundaries within greater Adelaide.

Results

Northern Adelaide is a region of greater relative disadvantage, demonstrated by the low Index of Relative Socio-Economic Disadvantage score (945) compared to the national average (1000) and scores for the central and southern Adelaide regions. Social determinants that contribute to this relative disadvantage include the proportion of people with no or limited education (26%) and those living on constrained income sources (e.g. unemployment benefits / aged pension, 10% and 72%, respectively). The northern Adelaide region has higher burdens of long-term health conditions including but not limited to diabetes, heart disease, kidney disease and lung diseases. We demonstrate that the comparatively high prevalence of obesity (37%) for people in the north of Adelaide were correlated with low numbers of people with adequate fruit intake (48%) and the higher proportion of people who currently smoke (16%) and who undertake low or no levels of exercise (73%).

Conclusions

Social disadvantage in the northern Adelaide region compared to the less disadvantaged central and southern regions of Adelaide is associated with poorer health outcomes and correlated with higher levels of health risk behaviours. Understanding the challenges within this local community setting may provide opportunities for local health networks to lead interventions to mitigate social risks and thereby improve health outcomes in this population.

Short Key Question Summary

What is known about the topic?

Social disadvantage is correlated with poor health outcomes

What does this paper add?

Profiles the types and prevalence of social determinants of health and the health status of a community region within an Australian capital city.

What are the implications for practitioners?

This profile of adverse social determinants of health relevant to the local community setting provides a context for the health system to respond, advocate for and intervene effectively to improve the well-being needs of this disadvantaged community.
Between-networks hyperconnectivity is induced by beta-amyloid and may facilitate tau spread
Authors: Hojjati Seyed Hani , Butler Tracy A. , Leon Mony de , Gupta Ajay , Nayak Siddharth , Luchsinger José A. , Chiang Gloria C. , Razlighi Qolamreza R.
Published: January 2024

Alzheimer’s disease (AD) is characterized by the buildup of neurofibrillary tau tangles and beta-amyloid (Aβ) plaques. While it has been hypothesized that Aβ facilitates the spread of tau outside of the medial temporal lobe (MTL), the specific pathological processes and mechanisms by which this occurs remain poorly understood. Our study employed advanced neuroimaging techniques, integrating 18F-Florbetaben Aβ and 18F-MK6240 tau positron emission tomography (PET) with resting-state functional magnetic resonance imaging (rs-fMRI) to characterize these mechanisms in two distinct datasets, that included 481 healthy elderly subjects, 46 of whom came with longitudinal data. Our research highlighted an intricate internetwork relationship between Aβ and tau accumulation, across spatially distinct functional networks. Additionally, we observed compelling evidence supporting the existence of a compensatory mechanism triggered by Aβ accumulation, resulting in hyperconnectivity between functional networks. Finally, the longitudinal findings indicate that between-networks hyperconnectivity is associated with future tau elevation and mediates the relationship between cortical Aβ and early-stage tau. Understanding this early brain alteration in response to the accumulation of Aβ could guide treatments early in the disease course and potentially prevent future tau accumulation.
Malaria and other risk factors for malnutrition, and the impact of intermittent preventive therapy for malaria on nutritional status of school-age children in Tanzania. A cross-sectional survey and a randomized controlled open-label trial
Authors: Hhera Jeremiah John , Makenga Geofrey , Van geertruyden Jean-Pierre
Published: January 2024

Background

WHO and the Lancet reported that malaria and malnutrition form a double health burden in low and middle-income countries. Despite the massive implementation of several malaria interventions, there is limited information on the impact of intermittent preventive therapy (IPTsc) for malaria on the nutritional status of school-age children.

Objective

To determine malnutrition risk factors and evaluate the impact of IPTsc for malaria on the nutritional status of school-age children in North-East Tanzania.

Methods

We analyzed secondary data from a cross-sectional baseline survey and a randomized controlled open-label trial. Study participants were randomized to three treatment groups and thereafter followed for 20 months. Data were analyzed using logistic regression and a linear mixed model.

Findings

At baseline, the prevalence of malaria was 27%. 23% of ≤10 years children were underweight, 21% were stunted, and 28% were either thin or severely thin. The odds of stunting were 78% higher (AOR=1.78, 95%CI=[1.36, 2.33], P<0.001) among children who had malaria compared to those who did not. Children from low socioeconomic status (SES) had higher odds of being underweight (AOR=1.50, 95%CI=[1.13,2.01], P=0.006) compared to their high SES counterparts. During the intervention, change in mean weight, height, and BMI over time as estimated from age-treatment interaction was not significantly different in the DP and ASAQ treatment groups compared to the control group. A unit change in age increased weight, height, and BMI by 2.2 units (p-value<0.001), 3.3 units (p-value<0.001), and 0.5 units (p-value<0.001). The height and weight in female children were higher compared to that of male children by 1 unit (p-value<0.001) and 0.8 unit (p-value<0.001), respectively.

Conclusion

The burden of malaria and malnutrition in this study’s setting is remarkable. Instead of focusing only on malaria, public health agencies should reinforce nutritional programs by collaborating with local communities to ensure food availability in schools and provide sustainable nutritional education to the local community members.
Sexually Transmitted Infections Among Patients on Antiretroviral Treatment at Adama Hospital Medical College, Adama, Ethiopia
Authors: Sento Midekso , Negera Atoma , Negera Samuel
Published: January 2024

Background

Sexually transmitted infections (STIs) are an infections or clinical syndromes caused by microorganisms that can be acquired and transmitted via sexual contact. Sexually transmitted infections are a major public health problem worldwide that cause acute illness, long-term complications, infertility, medical as well as psychological consequences, and death. Moreover, it facilitates the spread of the human immunodeficiency virus (HIV). To develop policies and strategies targeted at preventing and controlling illnesses, research on sexually transmitted infections in general and among people with HIV in particular is crucial.

Objective

to determine the prevalence and associated factors of sexually transmitted infections among human immunodeficiency virus patients in antiretroviral treatment clinic in Adama Hospital Medical College (AHMC), Adama, Ethiopia, 2022.

Methods

an institution-based, retrospective cross-sectional study design among 376 HIV patients in Anti-retroviral treatment clinic in AHMC was conducted on January-February, 2022. Study participants were selected using a systematic sampling. Data was collected using a structured questionnaire and was taken from individual cards with a prepared checklist. The collected data was processed and analyzed with Statistical Package for Social Science (SPSS) version 25.0. Descriptive statistical analyses were done to define the characteristics of the participants. Variables with p-value ≤0.25 in the bivariable analyses were entered into the multivariable logistic regression analysis to identify factors associated with STIs. Adjusted Odds Ratio (aOR) with a 95% Confidence Interval (CI) was computed and variable with a p-value less than 0.05 was declared as statistically significant variable.

Results

among 376 HIV positive patients 39 (10.37%) have STI and among them, 66.7% were female patients. Those under 35 years had 3.03 times more STI (aOR=3.03; 95% CI: (1.3, 6.66)) than those above 35 years. Those with CD4 of <500 had 11.7 times (aOR-=11.7; 95% C: (4.6, 30)) more STI than those with CD4 of > 500. Those with multiple sexual partners had 9.2 times (aOR=9.2; 95% CI: (2.7, 30.8)) more STI than those without multiple partners.

Conclusion

the study revealed among 376 HIV-positive patients 39(10.37%) have STI and 337 (89.63%) have no STI. Age (lower age group), having multiple sexual partners, and lower CD4 count were the factors significantly associated with STIs. Thus, we recommend health workers should take time in counseling ART patients about STI in every visit.
Valid inference for machine learning-assisted GWAS
Authors: Miao Jiacheng , Wu Yixuan , Sun Zhongxuan , Miao Xinran , Lu Tianyuan , Zhao Jiwei , Lu Qiongshi
Published: January 2024

Machine learning (ML) has revolutionized analytical strategies in almost all scientific disciplines including human genetics and genomics. Due to challenges in sample collection and precise phenotyping, ML-assisted genome-wide association study (GWAS) which uses sophisticated ML to impute phenotypes and then performs GWAS on imputed outcomes has quickly gained popularity in complex trait genetics research. However, the validity of associations identified from ML-assisted GWAS has not been carefully evaluated. In this study, we report pervasive risks for false positive associations in ML-assisted GWAS, and introduce POP-GWAS, a novel statistical framework that reimagines GWAS on ML-imputed outcomes. POP-GWAS provides valid statistical inference irrespective of the quality of imputation or variables and algorithms used for imputation. It also only requires GWAS summary statistics as input. We employed POP-GWAS to perform the largest GWAS of bone mineral density (BMD) derived from dual-energy X-ray absorptiometry imaging at 14 skeletal sites, identifying 89 novel loci reaching genome-wide significance and revealing skeletal site-specific genetic architecture of BMD. Our framework may fundamentally reshape the analytical strategies in future ML-assisted GWAS.
Neurometabolic dysfunction in psychosis observed with 7 T MRS
Authors: Schallmo Michael-Paul , Demro Caroline , Killebrew Kyle W. , Olman Cheryl A. , Sponheim Scott R. , Marjańska Małgorzata
Published: January 2024

Altered brain chemistry is thought to contribute to impairments in cognitive and perceptual functioning in people with psychotic psychopathology (PwPP). As heritable genetic factors shape the development of psychosis, these alterations in brain chemistry may extend to biological relatives of PwPP. Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantifying the concentration of various neurochemicals in the human brain. A number of MRS studies in different brain regions have been performed in PwPP, and to a lesser extent in relatives, but results have been largely mixed. There are a number of methodological issues that may have influenced previous findings. We show here that when such issues are addressed, MRS reveals a pattern of neurometabolic dysfunction in PwPP. We acquired MRS data at 7 tesla with an ultra-short echo time (TE = 8 ms) sequence in both occipital and prefrontal cortices from 43 healthy controls, 42 first-degree biological relatives, and 64 PwPP. We saw reduced levels ofN-acetyl-aspartate (NAA) in the occipital lobe in PwPP and their relatives (versus controls), and lowerN-acetyl-aspartyl-glutamate (NAAG) in prefrontal cortex in PwPP versus controls. Surprisingly, we also saw markedly increased levels of glucose in both occipital and prefrontal cortices in PwPP. Hierarchical clustering analyses showed that higher glucose levels were linked to higher psychiatric symptom levels and impairments in visual task performance. Together, our findings point to a disruption in neural metabolism across multiple brain areas in PwPP that is associated with impaired cognitive and perceptual functioning.
Contact with young children is a major risk factor for pneumococcal colonization in older adults
Authors: Wyllie Anne L. , Yolda-Carr Devyn , Hislop Maikel S. , Mbodj Sidiya , Wurst Loren , Waghela Pari , Alexander-Parrish Ronika , Grant Lindsay R. , Arguedas Adriano , Gessner Bradford D. , Weinberger Daniel M.
Published: January 2024

Background

Important questions remain about the sources of transmission of pneumococcus to older adults in the community. This is a critical question for understanding the potential indirect effects of using pneumococcal conjugate vaccines (PCVs) in children and older adults. For non-institutionalized individuals, the most likely source of adult-to-adult transmission is in the household. The goal of this study was to characterize the dynamics and risk factors for acquisition of pneumococcus in older adults.

Methods

We designed a longitudinal study to sample adults >60 years of age living in the same household (New Haven, CT, USA), and without younger contacts residing in the household. Saliva samples and questionnaires regarding social behaviors and health status were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genespiaBandlytA.

Results

Across two study seasons (November 2020-August 2021, November 2021-September 2022), 121 individuals from 61 households were followed for 6 study visits; 62 individuals were enrolled in both seasons. Overall, 52/1088 (4.8%) samples tested positive for pneumococcus based onpiaB, with 27/121 (22.3%) individuals colonized on at least one time point. Several individuals were colonized at multiple timepoints including two individuals who were colonized throughout the 10-week sampling period; two others were colonized at 5 of 6 time points. In 5 instances, both members of the household were carriers in the same season, though not necessarily at the same time point. Pneumococcal carriage was substantially higher among individuals who had contact with children (10.0% vs 1.6%). Participants who reported recent contact with <5-year-olds and 5-9-year-olds had particularly elevated prevalence (13.8%; 14.1%, respectively).

Conclusions

Contact with young children was the most important factor that influenced pneumococcal acquisition rates. While there were several instances where both adult household members were colonized at the same time or at sequential visits, these individuals also both typically had contact with children.
The Struggle to Vaccinate: Unveiling the Reality of the first year of Covid-19 Vaccination in the Democratic Republic of Congo
Authors: Adidja Amani , Aimé Cikomola Mwana Bene , Lungoyo Luhata Christophe , Kabwaya Mukoka Arsène , Lekeumo Cheuyem Fabrice Zobel , Mpinganjira Samuel , Sibongile Nkosi Dumisile , Chido Konono Kimberly Cheryl , Ngigi Michael , Ongolo-Zogo Pierre
Published: January 2024

Introduction

The emergence of COVID-19 as a global pandemic has affected countries worldwide, including the Democratic Republic of Congo (DRC). The DRC has experienced four waves of COVID-19, each associated with a new variant of the virus. To control the spread of the virus, the government of the DRC implemented various measures, including vaccination. The country developed a COVID-19 vaccine deployment plan, targeting high-risk groups, and launched a vaccination campaign in April 2021. This study aims to comprehensively assess the COVID-19 vaccination program in the DRC during its first year of implementation, including progress, coverage, types of vaccines administered, and a comparison with other neighboring countries.

Methods

This study was an analysis of the COVID-19 vaccination data during its first year of implementation in DRC. Data were collected from multiple sources, including the Ministry of Health and the WHO, and analyzed using descriptive statistics. The study received clearance and used de-identified and aggregated data.

Results

Out of the 26 provinces in the country, only 15 began immunization activities with varying levels of coverage, ranging from 0.02% to 6.91%. The number of functional vaccination sites remained patchy across the country. By March 2022, 5.7% of the population had received at least one vaccine dose, with 1.03% fully vaccinated. In most provinces, men were more compliant with vaccination than women. More than half of the vaccinated individuals preferred the Janssen vaccine. Compared to neighboring countries, the DRC has lagged behind in its vaccination efforts, having administered only 1.1 million of doses received (8%) and has vaccinated only 2% of its population with at least one dose, the lowest among the countries analyzed.

Conclusion

Despite the challenges faced in the first year of the COVID-19 vaccination, DRC has made significant progress in vaccinating its population. The slow progress highlights the need for continued investment in health systems. These insights can inform future Covid-19 vaccination campaigns in DRC and other low-income countries.
Multi-omics profiling with untargeted proteomics for blood-based early detection of lung cancer
Authors: Koh Brian , Liu Manway , Almonte Rebecca , Ariad Daniel , Bundalian Ghristine , Chan Jessica , Choi Jinlyung , Chou Wan-Fang , Cuaresma Rea , Hoedt Esthelle , Hopper Lexie , Hu Yuntao , Jain Anisha , Khaledian Ehdieh , Khin Thidar , Kokate Ajinkya , Lee Joon-Yong , Leung Stephanie , Lin Chi-Hung , Marispini Mark , Malekpour Hoda , Mora Megan , Mudaliar Nithya , Golmaei Sara Nouri , Qian Hao , Ramaiah Madhuvanthi , Ramaswamy Saividya , Ranjan Purva , Shu Guanhua , Spiro Peter , Ta Benjamin , Vitko Dijana , Waiss Jacob , Yanagihara Zachary , Zawada Robert , Zeng Jimmy Yi , Zhang Susan , Yee James , Blume John E. , Belthangady Chinmay , Wilcox Bruce , Ma Philip
Published: January 2024

Blood-based approaches to detect early-stage cancer provide an opportunity to improve survival rates for lung cancer, the most lethal cancer world-wide. Multiple approaches for blood-based cancer detection using molecular analytes derived from individual ‘omics (cell-free DNA, RNA transcripts, proteins, metabolites) have been developed and tested, generally showing significantly lower sensitivity for early-stage versus late-stage cancer. We hypothesized that an approach using multiple types of molecular analytes, including broad and untargeted coverage of proteins, could identify biomarkers that more directly reveal changes in gene expression and molecular phenotype in response to carcinogenesis to potentially improve detection of early-stage lung cancer. To that end, we designed and conducted one of the largest multi-omics, observational studies to date, enrolling 2513 case and control subjects. Multi-omics profiling detected 113,671 peptides corresponding to 8385 protein groups, 219,729 RNA transcripts, 71,756 RNA introns, and 1801 metabolites across all subject samples. We then developed a machine learning-based classifier for lung cancer detection comprising 682 of these multi-omics analytes. This multi-omics classifier demonstrated 89%, 80%, and 98-100% sensitivity for all-stage, stage I, and stage III-IV lung cancer, respectively, at 89% specificity in a validation set. The application of a multi-omics platform for discovery of blood-based disease biomarkers, including proteins and complementary molecular analytes, enables the noninvasive detection of early-stage lung cancer with the potential for downstaging at initial diagnosis and the improvement of clinical outcomes.
Are socio-demographic factors associated with electronic Health Information System utilization?A cross sectional study of the District Health Information System -2 (DHIS-2) in Burundi
Authors: Yandemye Innocent , Nimubona Alexandre
Published: January 2024

The utilization of Electronic Health Information System is crucial in informing credible decision-making process, especially in developing countries. We aimed to investigate the socio-demographic factors of Health workers that are associated with their utilization of the DHIS-2 platform in Burundi. We conducted a cross-sectional study amongst health workers involved in collecting and validating data in health facilities. The male gender was more associated with the DHIS-2 effect on the enhancement of health information access (χ2 = 7.995, P=.005) than the female gender. Marital status was associated with quality information (χ2 = 6.437, P= .011) and health information management (χ2= 5.053, P= .025) improvement. The lower time travel to workplace was associated with the improvement of quality information (χ2= 11.224, P= .001) and health information management (χ2= 6.568, P= .010), training on DHIS-2 (χ2= 16.374, P= .000), DHIS-2 compatibility with health facility management tools (χ2 = 4.726, P= .030), national health information system design (χ2= 8.023, P= .005), compatibility with primary health information tools (χ2= 9.339, P= .002) and the national health policy objective (χ2= 9.699, P= .002), required security elements (χ2= 14.205, P= .000), data transfer security (χ2= 6.288, P= .012), data protection against modification (χ2= 6.497, P= .011), and assurance of personal privacy (χ2= 7.650, P= .006). The lower educational level was associated with information error minimization (χ2= 7.243, P= .007) and learning ease (χ2 = 4.175, P= .041). The health worker function was associated with DHIS-2 compatibility with national health policy objective (χ2 =4.496, P= .034). The geographical area of work was associated with DHIS-2 ease of use and interoperability assurance (χ2 = 10.287, P= .006; χ2 = 16.086, P= .000). There is a need to make the use of the DHIS-2 platform a global public health concern in fragile health systems for robust decision-making process.
Racial Differences in the Relationship Between Blood Pressure and Cognitive Decline
Authors: Oliver Michael D. , Morrison Cassandra , El-Hulu Sondos , Harvey Marquinta , Barnes Lisa L.
Published: January 2024

Background

Cognition may be influenced by health-related factors such as blood pressure (BP). However, variations in BP may differentially affect cognition as a function of race. This study investigates the relationship between normal, high, and variable BP and cognitive decline in older Black and White adults.

Methods

2284 participants (1139 Blacks, 1145 Whites,MAge=73.4,SD=6.6) from 3 harmonized cohorts of older adults from the Rush Alzheimer’s Disease Center, were divided into 3 groups (normal, high, variable) based on systolic BP mean and standard deviation. Cognitive scores were computed from multiple assessments in 5 domains (i.e., episodic memory, semantic memory, working memory, processing speed, visuospatial ability). Performance across 19 tests were averaged to create a measure of global cognition. Linear mixed-effects models examined racial differences between BP and cognitive change over an average of 6.7 years.

Results

White adults with high or variable BP had faster rates of decline in global cognition compared to Black adults. White adults with high BP declined faster in perceptual speed, semantic memory, and working memory compared to Black adults with high BP, whereas White adults with variable BP had faster rates of decline in all cognitive domains compared to Black adults with variable BP. No racial differences were observed in individuals with normal BP.

Conclusions

White older adults with elevated or fluctuating BP show faster rates of cognitive decline compared to older Black adults. Findings highlight the complex interplay between BP and cognitive health, emphasizing the need for targeted interventions to address racial disparities in cognitive well-being.
Regression with race-modifiers: towards equity and interpretability
Authors: Kowal Daniel R.
Published: January 2024

The pervasive effects of structural racism and racial discrimination are well-established and offer strong evidence that the effects of many important variables on health and life outcomes vary by race. Alarmingly, standard practices for statistical regression analysis introduce racial biases into the estimation and presentation of these race-modified effects. We advocateabundance-based constraints(ABCs) to eliminate these racial biases. ABCs offer a remarkable invariance property: estimates and inference for main effects are nearly unchanged by the inclusion of race-modifiers. Thus, quantitative researchers can estimate race-specific effects “for free”—without sacrificing parameter interpretability, equitability, or statistical efficiency. The benefits extend to prominent statistical learning techniques, especially regularization and selection. We leverage these tools to estimate the joint effects of environmental, social, and other factors on 4th end-of-grade readings scores for students in North Carolina (n= 27, 638) and identify race-modified effects for racial (residential) isolation, PM2.5exposure, and mother’s age at birth.
Digital gait outcomes for ARSACS: discriminative, convergent and ecological validity in a multi-center study (PROSPAX)
Authors: Beichert Lukas , Ilg Winfried , Kessler Christoph , Traschütz Andreas , Reich Selina , Santorelli Filippo M. , Başak Ayşe Nazli , Gagnon Cynthia ,   PROSPAX consortium, Schüle Rebecca , Synofzik Matthis
Published: January 2024

Background

With treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multi-center validity, and ideally also ecological validity during free walking outside laboratory settings.

Methods

Cross-sectional multi-center study (4 centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public space. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (i.e. clinical and patient-relevance) validity by correlations with SPRSmobility(primary outcome) and SARA, SPRS and FARS-ADL (exploratory outcomes).

Results

Of 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff’s δ| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ=0.98), SPcmp (δ=0.94) and Swing CV (δ=0.93). Large correlations with the SPRSmobilitywere observed for Swing CV (Spearman’s ρ = 0.84), Speed (ρ=-0.63) and Harmonic Ratio V (ρ=-0.62). During supervised free walking in public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobilitywere here observed for Swing CV (ρ=0.78) and Speed (ρ=-0.69), without reductions in effect sizes compared to lab settings.

Conclusion

We identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multi-center settings, correlating with patient-relevant health aspects, and with high validity also outside lab settings, thus simulating real-life walking with higher ecological validity.
Coronary Artery Calcium Scans Powered by Artificial Intelligence Predicts Atrial Fibrillation Comparably to Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Naghavi Morteza , Reeves Anthony P. , Atlas Kyle , Li Dong , Goodarzynejad Hamidreza , Zhang Chenyu , Atlas Thomas , Henschke Claudia , Budoff Matthew J. , Yankelevitz David
Published: January 2024

Background

Applying artificial intelligence to coronary artery calcium computed tomography scan (AI-CAC) provides more actionable information beyond the Agatston coronary artery calcium (CAC) score. We have recently shown that AI-CAC automated left atrial (LA) volumetry enabled prediction of atrial fibrillation (AF) in as early as one year. In this study we evaluated the performance of AI-CAC automated LA volumetry versus LA volume measured by human experts using cardiac magnetic resonance imaging (CMRI) for predicting AF, and compared them with CHARGE-AF risk score, Agatston score, and NT-proBNP (BNP).

Methods

We used 15-year outcome data from 3552 asymptomatic individuals (52.2% women, ages 45-84 years) who underwent both CAC scans and CMRI in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA). AI-CAC took on average 21 seconds per scan. CMRI LA volume was previously measured by human experts. Data on BNP, CHARGE-AF risk score and the Agatston score were obtained from MESA.

Results

Over 15 years follow-up, 562 cases of AF accrued. The ROC AUC for AI-CAC versus CMRI and CHARGE-AF were not significantly different (AUC 0.807, 0.808, 0.800 respectively, p=0.60). The AUC for BNP (0.707) and Agatston score (0.694) were significantly lower than the rest (p<.0001). AI-CAC and CMRI significantly improved the continuous Net Reclassification Index (NRI) for prediction of AF when added to CHARGE-AF risk score (0.28, 0.31), BNP (0.43, 0.32), and Agatston score (0.69, 0.41) respectively (p for all<0.0001).

Conclusion

AI-CAC automated LA volumetry and CMRI LA volume measured by human experts similarly predicted incident AF over 15 years.
Functional connectivity of the nucleus accumbens predicts clinical course in treated and non-responder adult ADHD
Authors: Zaher Ahmed , Leonards Jan , Reif Andreas , Grimm Oliver
Published: January 2024

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood, contributing to a challenging trajectory characterised by increased rates of psychiatric comorbidity. Contrary to previous assumptions, the clinical course of ADHD in adulthood is characterised by dynamic changes influenced by stimulant treatment. To improve the precision of treatment, the identification of a predictive neuroimaging biomarker would be of great clinical importance.

In this study, we explore the potential of seed-based functional connectivity (FC) as a predictive tool for assessing the clinical course of ADHD symptoms. We conducted a longitudinal follow-up study of 54 adult ADHD patients who underwent magnetic resonance imaging (MRI) using a 3 Tesla scanner. All patients received stimulant treatment during an initial run-in period. After an average of three years, only subjective responders continued treatment (n=34), while subjective non-responders discontinued medication (n=20). We reassessed patients after three years of treatment to 1) evaluate the prediction of individual outcome by baseline fMRI and 2) to investigate differences in prediction by baseline fMRI depending on long-term treatment vs. discontinuation.

Our investigation focused on determining whether a relationship could be established between resting-state FC of the nucleus accumbens (NAc) and the trajectory of symptom development, as well as identifying possible differences in FC between individuals who had been on long-term stimulant treatment and those who had not used stimulants at the time of follow-up.

In general, reduced FC between the NAc and the default mode network (DMN) was associated with initially higher symptom burden, whereas patterns of improvement correlated with reduced FC between the NAc and the salience network (SN).

Comparatively, higher FC between the NAc and the SN was associated with better symptom outcomes in patients receiving long-term stimulant medication, whereas lower FC between the NAc and the SN was correlated with a more favourable prognosis in non-responders.

Our prospective fMRI study suggests that functional connectivity between the dopaminergic reward circuitry and the SN, especially the insula, is predictive of better ADHD symptom outcomes. This work highlights the potential of dopaminergic functional connectivity as a prognostic factor in ADHD. While future research with larger samples and longer follow-up is warranted, our study highlights the role of the NAc in the prognosis of ADHD.
Association between antinuclear antibodies (ANA) patterns and extractable nuclear antigens (ENA) in patients with autoimmune diseases
Authors: Haris Abdul Rehman , Tipu Hamid Nawaz , Ahmed Dawood , Nabeel Muhammad Abdullah , Akhtar Muhammad Shoaib
Published: January 2024

Background

Antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) are crucial biomarkers for the diagnosis of autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), Sjogren’s syndrome, systemic sclerosis, and polymyositis. In the present study, we assessed the most frequent ANA patterns associated with the most detectable ENA antigen (Ag) that could be used as a diagnostic and efficient prognostic marker of AID.

Materials and Methods

The primary objective of this study was to investigate the association between immunofluorescence (IF) ANA and ENA in patients with AIDs. This was a retrospective cross-sectional study. The study was performed at the Immunology Department of the Armed Forces Institute of Pathology, Rawalpindi. Retrospective data from 76 patients were tested for ANA and ENA from June 2020 to Nov 2020.

Results

A total of 76 patients comprising 14 (18.4%) males and 62(81.6%) females were tested for AIDs. The most frequent pattern among AID patients was coarse speckled, followed by the peripheral ANA pattern. The most frequent ENA Ags were Sjogren’s syndrome A (SSA) and B (SSB). SSA was significantly associated with coarse speckled and peripheral ANA patterns, whereas SSB was associated with coarse speckled ANA patterns. These associations are relevant for accurate diagnosis of autoimmune diseases.

Conclusion

SSA was associated with coarse speckled and peripheral ANA patterns, whereas SSB was associated with coarse speckled ANA patterns. The ANA patterns were significantly associated with ENA antigens.
Dual-energy X-ray absorptiometry derived knee shape may provide a useful imaging biomarker for predicting total knee replacement: findings from a study of 37,843 people in UK Biobank
Authors: Beynon Rhona A , Saunders Fiona R , Ebsim Raja , Frysz Monika , Faber Benjamin G , Gregory Jennifer S , Lindner Claudia , Sarmanova Aliya , Aspden Richard M , Harvey Nicholas C , Cootes Timothy , Tobias Jonathan H
Published: January 2024

Objective

We developed a novel imaging biomarker derived from knee dual-energy x-ray absorptiometry (DXA) to predict subsequent total knee replacement (TKR). The biomarker is based on knee shape, determined through statistical shape modelling. It was developed and evaluated using data and scans from the UK Biobank cohort.

Methods

Using a 129-point statistical shape model (SSM), knee shape (B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of DXA images. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with the risk of TKR, adjusted for age, sex, height and weight.

Results

The analysis included 37,843 individuals (mean 63.7 years). In adjusted models, B-score and mJSW were associated with TKR: a standard deviation increase in B-score was associated with a hazard ratio (HR) of 2.32 (2.13, 2.54), and a lower mJSW with a HR of 2.21 (1.76, 2.76). In the 6,719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In subsequent ROC analyses, a model combining B-score, osteophyte score, and demographic variables had superior discrimination (AUC=0.87) in predicting TKR at five years compared with a model with demographic variables alone (AUC=0.73).

Conclusions

An imaging biomarker derived from knee DXA scans reflecting knee shape and osteophytes, in conjunction with demographic factors, could help identify those at high risk of TKR, in whom preventative strategies should be targeted.