bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissues as networks of cells: towards generative rules of complex organ development
Authors: Fischer Sabine C. , Bassel George W. , Kollmannsberger Philip
Published: July 2023

Network analysis is a well-known and powerful tool in molecular biology. More recently, it has been introduced in developmental biology. Tissues can be readily translated into spatial networks such that cells are represented by nodes and intercellular connections by edges. This discretization of cellular organization enables mathematical approaches rooted in network science to be applied towards the understanding of tissue structure and function. Here, we describe how such tissue abstractions can enable the principles that underpin tissue formation and function to be uncovered. We provide an introduction into biologically relevant network measures, then present an overview of different areas of developmental biology where these approaches have been applied. We then summarize the general developmental rules underpinning tissue topology generation. Finally, we discuss how generative models can help to link the developmental rule back to the tissue topologies. Our collection of results points at general mechanisms as to how local developmental rules can give rise to observed topological properties in multicellular systems.
Maximum mutational robustness in genotype–phenotype maps follows a self-similar blancmange-like curve
Authors: Mohanty Vaibhav , Greenbury Sam F. , Sarkany Tasmin , Narayanan Shyam , Dingle Kamaludin , Ahnert Sebastian E. , Louis Ard A.
Published: July 2023

Phenotype robustness, defined as the average mutational robustness of all the genotypes that map to a given phenotype, plays a key role in facilitating neutral exploration of novel phenotypic variation by an evolving population. By applying results from coding theory, we prove that the maximum phenotype robustness occurs when genotypes are organized as bricklayer’s graphs, so-called because they resemble the way in which a bricklayer would fill in a Hamming graph. The value of the maximal robustness is given by a fractal continuous everywhere but differentiable nowhere sums-of-digits function from number theory. Interestingly, genotype–phenotype maps for RNA secondary structure and the hydrophobic-polar (HP) model for protein folding can exhibit phenotype robustness that exactly attains this upper bound. By exploiting properties of the sums-of-digits function, we prove a lower bound on the deviation of the maximum robustness of phenotypes with multiple neutral components from the bricklayer’s graph bound, and show that RNA secondary structure phenotypes obey this bound. Finally, we show how robustness changes when phenotypes are coarse-grained and derive a formula and associated bounds for the transition probabilities between such phenotypes.
X chromosome drive is constrained by sexual selection and influences ornament evolution
Authors: Paczolt Kimberly A. , Welsh Gabrielle T. , Wilkinson Gerald S.
Published: July 2023

Experimental evolution provides an integrative method for revealing complex interactions among evolutionary processes. One such interaction involves sex-linked selfish genetic elements and sexual selection. X-linked segregation distorters, a type of selfish genetic element, influence sperm transmission to increase in frequency and consequently alter the population sex ratio and the opportunity for sexual selection, while sexual selection may impact the spread of X-linked distorters. Here we manipulated sexual selection by controlling female mating opportunities and the presence of a distorting X chromosome in experimental lines of the stalk-eyed fly,
Teleopsis dalmanni
, over 11 generations
.
We find that removal of sexual selection leads to an increase in the frequency of the X-linked distorter and sex ratio across generations and that post-copulatory sexual selection alone is sufficient to limit the frequency of distorters. In addition, we find that male eyestalk length, a trait under pre-copulatory sexual selection, evolves in response to changes in the strength of sexual selection with the magnitude of the response dependent on X chromosome type and the frequency of distorting X chromosomes. These results reveal how a selfish X can interact with sexual selection to influence the evolution of sexually selected traits in multiple ways.
The price of being late: short- and long-term consequences of a delayed migration timing
Authors: Bontekoe Iris D. , Hilgartner Roland , Fiedler Wolfgang , Flack Andrea
Published: July 2023

Choosing the right migration timing is critical for migrants because conditions encountered
en route
influence movement costs, survival, and, in social migrants, the availability of social information. Depending on lifetime stages, individuals may migrate at different times due to diverging constraints, affecting the composition of migration groups. To examine the consequences of a delayed migration timing, we artificially delayed the migration of juvenile white storks (
Ciconia ciconia
) and thereby altered their physical and social environment. Using nearly continuous 1 Hz GPS trajectories, we examined their migration behaviour, ranging from sub-second level performance to global long-distance movement, in relation to two control groups. We found that delayed storks experienced suboptimal soaring conditions, but better wind support and thereby achieved higher flight speeds than control storks. Delayed storks had a lower mortality rate than the control storks and wintered closer to the breeding area. In fact, none of the delayed storks reached the traditional African wintering areas. Thus, our results show that juvenile storks can survive migrating at the ‘wrong’ time. However, this had long-term consequences on migration decisions. We suggest that, when timing their migration, storks balance not just energy and time, but also the availability of social information.
Task-dependent Alteration in Delta Band Corticomuscular Coherence during Standing in Chronic Stroke Survivors
Authors: Kukkar Komal K. , Rao Nishant , Huynh Diana , Shah Sheel , Contreras-Vidal Jose L. , Parikh Pranav J.
Published: July 2023

Balance control is an important indicator of mobility and independence in activities of daily living. How the changes in functional integrity of corticospinal tract due to stroke affects the maintenance of upright stance remains to be known. We investigated the changes in functional coupling between the cortex and lower limb muscles during a challenging balance task over multiple frequency bands in chronic stroke survivors. Eleven stroke patients and nine healthy controls performed a challenging balance task. They stood on a computerized platform with/without somatosensory input distortion created by sway-referencing the support surface, thereby varying the difficulty levels of the task. We computed corticomuscular coherence between Cz (electroencephalography) and leg muscles and assessed balance performance using Berg Balance scale (BBS), Timed-up and go (TUG) and center of pressure (COP) measures. We found lower delta frequency band coherence in stroke patients when compared with healthy controls under medium difficulty condition for distal but not proximal leg muscles. For both groups, we found similar coherence at other frequency bands. On BBS and TUG, stroke patients showed poor balance. However, similar group differences were not consistently observed across COP measures. The presence of distal versus proximal effect suggests differences in the (re)organization of the corticospinal connections across the two muscles groups for balance control. We argue that the observed group difference in the delta coherence might be due to altered mechanisms for the detection of somatosensory modulation resulting from sway-referencing of the support platform for balance control.
Physiological Perspective of Musculoskeletal Disorders among Older Peoples in Bangladesh
Authors: Jahan Sharmila , Islam Md. Rabiul , Rahman Tania , Kabir Md. Feroz , Hossain Md. Kabir , Hossain K M Amran , Hossain Md. Zahid , Rahman Ehsanur , Islam Md. Waliul , Chakrovorty Sonjit Kumar , Sarker Altaf Hossain , Moula Golam , Antara Atqiya
Published: July 2023

Musculoskeletal disorders are debilitating conditions that significantly impact on the state of health, especially in elderly people. The study, which employed a cross-sectional design and practical sampling, included 206 participants from all over Bangladesh with musculoskeletal issues of varying severity and impact. The study was carried out between January and June of 2022. The majority of them experienced musculoskeletal pain. It was also common to have limited mobility as a result of arthritic change, which eventually affected daily activities like taking care of oneself. To improve the health of the elderly female population, more study must be conducted to identify the many factors that contribute to musculoskeletal issues. The development of effective prevention and rehabilitation programs must then be based on this knowledge.
Replication of a neuroimaging biomarker for striatal dysfunction in psychosis
Authors: Rubio Jose M , Lencz Todd , Cao Hengyi , Kraguljac Nina , Dhamala Elvisha , Homan Philipp , Horga Guillermo , Sarpal Deepak K. , Argyelan Miklos , Gallego Juan , Cholewa John , Barber Anita , Kane John , Malhotra Anil
Published: July 2023

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n=101) from healthy controls (n=51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n=97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC=75.4%, 95%CI=67.0%-83.3%; in non-affective psychosis AUC=80.5%, 95%CI=72.1-88.0%, and in affective psychosis AUC=58.7%, 95%CI=44.2-72.0%). Test-retest reliability ranged between ICC=0.48 (95%CI=0.35-0.59) and ICC=0.22 (95%CI=0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC=0.51 (95%CI=0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 minutes, diagnostic classification of the FSA increased from AUC=71.7% (95%CI=63.1%-80.3%) to 75.4% (95%CI=67.0%-83.3%) and phase encoding direction reliability from ICC=0.29 (95%CI=0.14-0.43) to ICC=0.51 (95%CI=0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic – but not prognostic – biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.
Examining the Evolution and Drivers of COVID-19 Transmission Waves in Ghana, 2020 – 2022
Authors: Tamal Christopher Sunkwa , Ohene Sally-Ann , Okine Rafiq Nii , Adjabeng Michael , Guyo Argata Guracha , Osei-Sarpong Fred , Avevor Patrick , Owusu-Asare Ama Akyampoma , Asiedu-Bekoe Franklin , Kwarteng Gideon , Kuma-Aboagye Patrick , Kasolo Francis Chisaka
Published: July 2023

Background

Ghana reported the first COVID-19 cases on 12 March 2020. Response actions were rolled out along seven thematic pillars to limit the importation, detect and contain the virus, effectively manage cases, ensure effective coordination and maintain essential services. A whole-of-government and whole-of-society approach was adopted for the response. The government instituted restriction measures at various stages of the response to contain the pandemic or limit the impact of the pandemic on the health, social and economic wellbeing of the citizens. Four distinct transmission waves were recorded within the first 2 years of the pandemic. The study examined the key drivers of the major waves.

Methods

A descriptive analysis of the pandemic from March 2020 to March 2022 was conducted using data reported through the country’s COVID-19 surveillance platforms. All RT-PCR confirmed cases reported from the 16 administrative regions over the two-year period were analysed. The effective reproduction number was computed using a model developed by Cori and colleagues.

Results

A total of 160,761 cases with 99.1% (159,227) recoveries or discharges were reported as of 12 March 2022. The Greater Accra Region reported 56.3% of the confirmed cases. Within the period, 1,445 deaths (CFR= 0.9%) were reported. Approximately 2.3 million tests (76,774 per million population) tests were conducted with a cumulative test positivity rate of 6.8%. COVID-19 vaccination was enrolled a year after the first cases were reported and 21.3% of the target population was fully vaccinated as of 12 March 2022. Ghana recorded four major COVID-19 transmission waves characterized mainly by variants of concern and sub-optimal adherence to the public health and social measures.

Conclusion

Scaling up and enhancing community acceptance of COVID-19 vaccination as well optimizing the current surveillance and response systems are essential is sustaining the current gains and limiting the emergence of new variants of concern.
Cardiovascular Risks Associated with Patients Infected with Scrub Typhus: A Nationwide Cohort Study
Authors: Yeh Jih-Kai , Wu Victor Chien-Chia , Chen Shao-Wei , Wu Chia-Ling , Lin Yu-Sheng , Cheng Chun-Wen , Chang Chih-Hsiang , Wu Michael , Chu Pao-Hsien , Chang Shang-Hung , Huang Yu-Tung
Published: July 2023

Background

Scrub typhus is an infectious disease that affects multiple organs. However, the long-term cardiovascular (CV) risk in survivors remains unknown.

Method

A retrospective cohort study used administrative claims data from the National Health Insurance Research Database (NHIRD) to investigate the CV risk of scrub typhus survivors from January 1, 2010, to December 31, 2015. People who had prior CV events before the diagnosis of scrub typhus were excluded. The CV outcomes of interest were acute myocardial infarction (AMI), heart failure hospitalization (HFH), hemorrhagic or ischemic stroke, new-onset atrial fibrillation (AF), aneurysm or dissection of aorta, venous thromboembolism (VTE), and CV death.

Result

A total of 2,269 patients with scrub typhus and without a prior CV event were identified (mean age 47.8±16.1 years, 38.0% female). The health control cohort (n=2,264) was selected to compare by the frequency matching with age, gender, and co-morbidities with patients with scrub typhus. The incidence of HFH, new-onset AF, and total events was significantly higher among patients with scrub typhus than the control cohort with an adjusted hazard ratio (aHR) of 1.97, 95% confidence interval (CI) 1.13-3.42 for HFH; 2.48, 95% CI: 1.23-5.0 for new-onset AF; 1.43, 95% CI: 1.08-1.91 for total CV events, respectively. The event rates of other outcomes were similar between the two groups.

Conclusion

In the cohort study, survivors of scrub typhus are at heightened risk of subsequent CV events, especially for HFH and new-onset AF. These findings serve as an important reminder to physicians regarding the significant CV risk that remains present following acute scrub typhus infection.
Nocturnal hypertension and left ventricular diastolic dysfunction in diabetic patients with pre-heart failure phase: Prospective cohort HSCAA study
Authors: Kidawara Yonekazu , Kadoya Manabu , Igeta Masataka , Morimoto Akiko , Miyoshi Akio , Kakutani-Hatayama Miki , Kanzaki Akinori , Konishi Kosuke , Kusunoki Yoshiki , Daimon Takashi , Asakura Masanori , Ishihara Masaharu , Koyama Hidenori
Published: July 2023

Background

Diabetes is an important risk factor of heart failure (HF) and is associated with left ventricular (LV) diastolic dysfunction. However, integrated importance of diabetes and its comorbid conditions, such as altered nocturnal blood pressure (BP) variation, as predictors of diastolic dysfunction is not known in pre-HF period. The present study was conducted as longitudinal examination of the predictive value of nocturnal hypertension profiles on progression of LV diastolic dysfunction in diabetic and non-diabetic patients without heart diseases.

Methods

Pre-heart failure 422 subjects (154 diabetes, 268 non-diabetes) were followed for 36.8 ± 18.2 months. The relationships among the patterns of nocturnal hypertension and the outcome of LV diastolic dysfunction, defined as increase in E/e’ >14, were investigated in the patients with and without diabetes.

Results

The interaction effect of the diabetes status and the patterns of nocturnal hypertension on the hazard rate of the occurrence of E/e’>14 was statistically significant (p=0.017). Kaplan-Meier analysis results revealed that diabetic patients with non-dipper (p=0.016 vs. dipper) and riser (p=0.007 vs. dipper) had a significantly greater risk for a diastolic dysfunction event. Furthermore, multivariable Cox proportional hazards analysis revealed that non-dipper (HR: 3.00; 95% CI: 1.11–8.06, p = 0.029) and riser (HR: 3.58; 95% CI:1.24–10.35, p = 0.018) patterns were significantly associated with elevated risk of the outcome of LV diastolic dysfunction. In contrast, no similar significant associations were found in non-diabetic patients.

Conclusions

During pre-HF periods, nocturnal hypertension is an important predictor for progression of LV diastolic dysfunction in diabetic patients.

Non-standard Abbreviation and Acronyms

HSCAA: Hyogo Sleep Cardio-Autonomic Atherosclerosis
More than medications: A patient-centered assessment of Parkinson’s disease care needs during hospitalization
Authors: Shurer Jessica , Golden Shannon L. S. , Mihas Paul , Browner Nina
Published: July 2023

Background

Parkinson’s disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step towards the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population.

Objectives

This qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting.

Methods

Focus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and clinical team. Data was analyzed using inductive thematic analysis.

Results

A total of twelve PwPs and thirteen CPs participated in seven focus groups. Participants were 52% female and 28% nonwhite; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explores the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD.

Conclusion

PD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility of ambulation protocols and an environment that accommodated their disability. Findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes.
Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: microbiome-related factors associated with clinical outcome
Authors: Andreani Nadia Andrea , Sharma Arunabh , Dahmen Brigitte , Specht Hannah E. , Mannig Nina , Ruan Vanessa , Keller Lara , Baines John F. , Herpertz-Dahlmann Beate , Dempfle Astrid , Seitz Jochen
Published: July 2023

There is mounting evidence regarding the role of gut microbiota in anorexia nervosa (AN). Previous studies have reported that patients with AN show dysbiosis compared to healthy controls (HCs); however, the underlying mechanisms are unclear, and data on influencing factors and longitudinal course of microbiome changes are scarce. Here, we present longitudinal data of 57 adolescent inpatients diagnosed with AN at up to nine time points (including a 1-year follow-up examination) and compare these to up to six time points in 34 HCs. 16S rRNA gene sequencing was used to investigate the microbiome composition of fecal samples, and data on food intake, weight change, hormonal recovery (leptin levels), and clinical outcomes were recorded. Differences in microbiome composition compared to HCs were greatest during acute starvation and in the low-weight group, while diminishing with weight gain and especially weight recovery at the 1-year follow-up. Illness duration and prior weight loss were strongly associated with microbiome composition at hospital admission, whereas microbial changes during treatment were associated with kilocalories consumed, weight gain, and hormonal recovery. The microbiome at admission was prognostic for hospital readmission, and a higher abundance ofSutterellawas associated with a higher body weight at the 1-year follow-up. Identifying these clinically important factors further underlines the potential relevance of gut microbial changes and may help elucidate the underlying pathophysiology of gut-brain interactions in AN. The characterization of prognostically relevant taxa could be useful to stratify patients at admission and to potentially identify candidate taxa for future supplementation studies aimed at improving AN treatment.
Proteomic prediction of common and rare diseases
Authors: Carrasco-Zanini Julia , Pietzner Maik , Davitte Jonathan , Surendran Praveen , Croteau-Chonka Damien C. , Robins Chloe , Torralbo Ana , Tomlinson Christopher , Fitzpatrick Natalie , Ytsma Cai , Kanno Tokuwa , Gade Stephan , Freitag Daniel , Ziebell Frederik , Denaxas Spiros , Betts Joanna C. , Wareham Nicholas J. , Hemingway Harry , Scott Robert A. , Langenberg Claudia
Published: July 2023

Background

For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Whether measuring thousands of proteins offers predictive information across a wide range of diseases is unknown.

Methods

In 41,931 individuals from the UK Biobank Pharma Proteomics Project (UKB-PPP), we integrated ∼3000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81 – 6038 cases). We compared prediction models based on proteins with a) basic clinical information alone, b) basic clinical information + 37 clinical biomarkers, and c) genome-wide polygenic risk scores.

Results

For 67 pathologically diverse diseases, a model including as few as 5 to 20 proteins was superior to clinical models (median delta C-index = 0.07; range = 0.02 – 0.31) and to clinical models with biomarkers for 52 diseases. In multiple myeloma, for example, a set of 5 proteins significantly improved prediction over basic clinical information (delta C-index = 0.25 (95% confidence interval 0.20 – 0.29)). At a 5% false positive rate (FPR), proteomic prediction (5 proteins) identified individuals at high risk of multiple myeloma (detection rate (DR) = 50%), non-Hodgkin lymphoma (DR = 55%) and motor neuron disease (DR = 29%). At a 20% FPR, proteomic prediction identified individuals at high-risk for pulmonary fibrosis (DR= 80%) and dilated cardiomyopathy (DR = 75%).

Conclusions

Sparse plasma protein signatures offer novel, clinically useful prediction of common and rare diseases, through disease-specific proteins and protein predictors shared across multiple diseases.

(Funded by Medical Research Council, NIHR, Wellcome Trust.)
Worldwide trends in COVID-19 related attacks against healthcare
Authors: Duffhues Willeke , Barten Dennis , De Cauwer Harald , Mortelmans Luc , van Osch Frits , Tin Derrick , Koopmans Marion P.G. , Ciottone Gregory
Published: July 2023

Background

During the COVID-19 pandemic, violence targeting healthcare reportedly increased. Attacks against healthcare have the potential to impair the public health response and threaten the availability of healthcare services. However, there is little systematic understanding of the extent and characteristics of healthcare attacks in the setting of a pandemic. This study aimed to investigate global trends regarding COVID-19 related attacks against healthcare from January 2020 until January 2023.

Methodology

COVID-19 related incidents that occurred between January 2020 and January 2023 were extracted from the Safeguarding Health in Conflict Coalition database and screened for eligibility. Data collected per incident included temporal factors; country; setting; attack and weapon type; perpetrator; motive; number of healthcare workers (HCWs) and patients killed, injured or kidnapped; and whether the incident caused damage to a health facility.

Results

This study identified 255 COVID-19 related attacks against healthcare. The attacks occurred globally and throughout the course of the pandemic. Incidents were heterogeneous with regards to motives, attack types and outcomes. At least 18 HCWs were killed, 147 HCWs were injured and 86 facilities were damaged or destroyed. There were two periods with a peak incidence of reports. The first peak occurred during the beginning of the pandemic, and predominantly concerned stigma-related attacks against healthcare. The second peak, in 2021, was mainly composed of conflict-related attacks in Myanmar, and attacks targeting the global vaccination campaign.

Conclusion

COVID-19 related attacks against healthcare occurred globally and in a variety of settings throughout the course of the pandemic. The findings of this study can be used to prevent and mitigate healthcare attacks during the ongoing and future pandemics.
The effect of sleep-corrected social jetlag on crystalized intelligence, school performance, and functional connectome in early adolescence
Authors: Yang Fan Nils , Picchioni Dante , Duyn Jeff H.
Published: July 2023

Approximately half of adolescents encounter a mismatch between their sleep patterns on school days and free days, also referred to as “social jetlag”. This condition has been linked to various adverse outcomes, such as poor sleep, cognitive deficits, and mental disorders. However, prior research was unsuccessful in accounting for other variables that are correlated with social jetlag, including sleep duration and quality. To address this limitation, we applied a propensity score matching method on a sample of 8853 11-12-year-olds from the two-year follow-up (FL2) data of the Adolescent Brain Cognitive Development (ABCD) study. We identified 3366 pairs of participants with high sleep-corrected social jetlag (SJLsc, over 1 hour) and low SJLsc (<= 1 hour) at FL2, as well as 1277 pairs at three-year follow-up (FL3), after matching based on 11 covariates including socioeconomic status, demographics, and sleep duration and quality. Our results showed that high SJLsc, as measured by the Munich Chronotype Questionnaire, was linked to reduced crystallized intelligence, lower school performance - grades, and decreased functional connectivity between cortical networks and subcortical regions, specifically between cingulo-opercular network and right hippocampus (cerc-hprh). Further mediation and longitudinal mediation analyses revealed that cerc-hprh connection mediated the associations between SJLsc and crystallized intelligence at FL2, and between SJLsc and grades at both FL2 and FL3. We validated these findings by replicating these results using objective SJLsc measurements obtained via Fitbit watches. Overall, our study highlights the negative association between social jetlag and crystallized intelligence during early adolescence.
Utility of Point-of-Care Ultrasound in A Resource-Limited Health Care Setting in Southeast Ghana: A Needs Assessment
Authors: Mohamed Elfadil Mahmoud , Baraniecki-Zwil Gwen , Fowose Mobolaji H. , Schiff Julia , Munawar Maham , Panebianco Nova , Kramer Jeffrey A.
Published: July 2023

Background

Many proven benefits of point-of-care ultrasound (POCUS) are increasingly recognized, including being non-invasive, cost-effective, and of significant diagnostic value. Evidence for these benefits has been replicated in variable settings. However, litle is known about the utilization of POCUS in the developing world and in an out-of-hospital, resource-limited setting. This needs assessment study describes utilization of POCUS in rural Ghana.

Methods

We performed retrospective analysis of data from medical missions to Southeast Ghana, evaluating the utilization of POCUS in a rural resource-limited health setting. The first mission trip took place in the Oti region between January 25th, 2023, and February 1st, 2023. The second was in the Volta region between February 19th, 2023, and February 24th, 2023. These missions established out-of-hospital remote clinics for walk in patients who are informed about the clinic by the word of mouth by their community leaders and neighbors. We included all POCUS scans performed as part of those missions.

Findings

A total of 128 POCUS studies were performed and included in this analysis. Studies were performed for 111 patients (median age 23 years; 49.9% male). Twelve distinct types of sonographic studies were performed. Notably, 48.4% revealed significant findings that helped to confirm a working diagnosis and subsequently formulate or optimize plan of management. A therapeutic intervention was made based on US findings in 16.4% of encounters, while a referral to higher level of care was recommended in 27.3% of cases. Reassurance with ruling out a main differential diagnosis was the case in 7% of encounters.

Conclusion

POCUS is effective and can be utilized for a wide range of types of scans effectively in out-of-hospital resource-limited settings in rural Ghana with significant impact on clinical decision-making process.
Estimating the gap between clinical cholera and true community infections: findings from an integrated surveillance study in an endemic region of Bangladesh
Authors: Hegde Sonia , Khan Ashraf Islam , Perez-Saez Javier , Khan Ishtiakul Islam , Hulse Juan Dent , Islam Md Taufiqul , Khan Zahid Hasan , Ahmed Shakeel , Bertuna Taner , Rashid Mamunur , Rashid Rumuna , Hossain Md Zakir , Shirin Tahmina , Wiens Kirsten , Gurley Emily S. , Bhuiyan Taufiqur Rahman , Qadri Firdausi , Azman Andrew S.
Published: July 2023

Our understanding of cholera transmission and burden largely rely on clinic-based surveillance, which can obscure trends, bias burden estimates and limit the impact of targeted cholera-prevention measures. Serologic surveillance provides a complementary approach to monitoring infections, though the link between serologically-derived infections and medically-attended disease – shaped by immunological, behavioral, and clinical factors – remains poorly understood. We unravel this cascade in a cholera-endemic Bangladeshi community by integrating clinic-based surveillance, healthcare seeking, and longitudinal serological data through statistical modeling. We found >50% of the study population had aV. choleraeO1 infection annually, and infection timing was not consistently correlated with reported cases. Four in 2,340 infections resulted in symptoms, only one of which was reported through the surveillance system. These results provide new insights into cholera transmission dynamics and burden in the epicenter of the 7thcholera pandemic and provide a framework to synthesize serological and clinical surveillance data.
Impact of four years of annually repeated indoor residual spraying (IRS) with Actellic 300CS on routinely reported malaria cases in an agricultural setting in Malawi
Authors: Hoek Spaans Remy , Mkumbwa Albert , Nasoni Peter , Jones Christopher M. , Stanton Michelle C.
Published: July 2023

Indoor residual spraying (IRS) is one of the main vector control tools used in malaria prevention. This study evaluates IRS in the context of a privately run campaign conducted across a low-lying, irrigated, sugarcane estate from Illovo Sugar, in the Chikwawa district of Malawi. The effect of Actellic 300CS annual spraying over four years (2015-2018) was assessed using a negative binomial mixed effects model, in an area where pyrethroid resistance has previously been identified. With an unadjusted incidence rate ratio (IRR) of 0.38 (95% CI: 0.32 – 0.45) and an adjusted IRR of 0.50 (95% CI: 0.42-0.59), IRS has significantly contributed to a reduction in case incidence rates at Illovo, as compared to control clinics and time points outside of the six month protective period. This study shows how the consistency of a privately run IRS campaign can improve the health of employees. More research is needed on the duration and timing of IRS programmes.
Do people with disabilities have the same level of HIV knowledge and access to testing? Evidence from 513,252 people across 37 Multiple Indicator Cluster Surveys
Authors: Rotenberg Sara , Chen Shanquan , Hanass-Hancock Jill , Davey Calum , Banks Lena Morgon , Kuper Hannah
Published: July 2023

Background

Disability and HIV are intricately linked, as people with disabilities are at higher risk of contracting HIV and HIV can lead to impairments and disability. Despite this well-established relationship, there remains limited internationally comparable evidence on HIV knowledge and access to testing for people with disabilities.

Methods and Findings

We used cross-sectional data from 37 Multiple Indicator Cluster Surveys. 513,252 people were eligible for inclusion, including 24,695 (4.8%) people with disabilities. We examined risk ratios and their 95% confidence intervals for key indicators on HIV knowledge and access to testing for people with disabilities by sex and country. We also conducted a meta-analysis to get a pooled estimate for each sex and indicator. Men and women with disabilities were less likely to have comprehensive knowledge about HIV prevention (aRR: 0.74 [0.67, 0.81] and 0.75 [0.69, 0.83], respectively) and to know of a place to be tested for HIV (aRR: 0.95 [0.92, 0.99] and 0.94 [0.92, 0.97], respectively) compared to men and women without disabilities. Women with disabilities were also less likely to know how to prevent mother-to-child transmission (aRR: 0.87 [0.81, 0.93]) and ever have been tested for HIV (aRR: 0.90 [0.85, 0.94]), while men with disabilities showed some evidence of relative inequities for these indictors. There was also some evidence women with disabilities were less likely to be tested for HIV in the past year.

Conclusion

Men and women with disabilities face inequities in HIV knowledge and access to testing, particularly for women with disabilities. Governments must include people with disabilities in HIV programs by improving accessibility and increasing disability-inclusion in each health system building block.
Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19
Authors: Pierotti Livia , Cooper Jennifer , James Charlotte , Cassels Kenah , Gara Emma , Denholm Rachel , Wood Richard
Published: July 2023

Background

COVID-19 has had a significant impact on people’s mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this.

Methods

We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based ‘talking therapies’ (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare ‘do nothing’ (baseline) scenarios to ‘what if’ (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards.

Results

The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, results in demand being shifted to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand.

Conclusion

In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.
Two-Year Evaluation ofLegionellain an Aging Residential Building: Assessment of Multiple Potable Water Remediation Approaches
Authors: Lee-Masi Monica , Coulter Caroline , Chow Steven J. , Zaitchik Benjamin , Jacangelo Joseph G. , Exum Natalie G. , Schwab Kellogg J.
Published: July 2023

Legionellais an opportunistic waterborne pathogen that is difficult to eradicate in colonized drinking water pipes.Legionellacontrol is further challenged by aging water infrastructure and lack of evidence-based guidance for building treatment. This study assessed multiple premise water remediation approaches designed to reduceLegionella pneumophila (Lp)within a residential building located in an aging, urban drinking water system over a two-year period. Samples (n=745) were collected from hot and cold-water lines and quantified via most probable number culture. Building-level treatment approaches included three single heat shocks (HS), three single chemical shocks (CS), and continuous low-level chemical disinfection (CCD) in the potable water system. The building was highly colonized withLpwith 71%Lppositivity. Single HS had a statistically significantLpreduction one day post treatment but no significantLpreduction one, two, and four weeks post treatment. The first two CS resulted in statistically significantLpreduction at two days and four weeks post treatment, but there was a significantLpincrease at four weeks following the third CS. CCD resulted in statistically significantLpreduction ten weeks post treatment implementation. This demonstrates that in a building highly colonized withLp, sustained remediation is best achieved using CCD.

SYNOPSIS

Long-termLegionella control is difficult to maintain within aging premise plumbing. This study supports continuous low-level building treatment as an effective long-term remediation of a building highly colonized withLegionella.

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Genetic and phenotype analyses of primary lateral sclerosis datasets from international cohorts
Authors: Kalia Munishikha , Spargo Thomas P. , Al Khleifat Ahmad , Opie-Martin Sarah , Kabiljo Renata , Dobson Richard JB , van Damme Philip , Corcia Philippe , Couratier Philippe , Hardiman Orla , McLaughlin Russell , Gotkine Marc , Drory Vivian , Silani Vincenzo , Ticozzi Nicola , Veldink Jan H. , van den Berg Leonard H. , de Carvalho Mamede , Pinto Susana , Pardina Jesus S. Mora , Povedano Monica , Andersen Peter M. , Weber Markus , Başak Nazli A. , Shaw Christopher E , Shaw Pamela J. , Morrison Karen E. , Landers John E. , Glass Jonathan D. , Vourc’h Patrick ,   Project MinE ALS Sequencing Consortium, Al-Chalabi Ammar , Iacoangeli Alfredo
Published: July 2023

Primary lateral sclerosis (PLS) is the rarest form of motor neurone disease (MND). It is characterized by upper motor neuron degeneration, leading to progressive weakness, spasticity and functional disability. Although PLS does not typically shorten life substantially, it gradually impacts quality of life as the diseases progresses. There is no established genetic cause of PLS. One of the biggest challenges faced by people with PLS is delayed diagnosis and misdiagnosis, since the initial symptoms can be similar to amyotrophic lateral sclerosis (ALS), the most common form of MND. In the absence of a concrete genetic test that differentiates PLS from other MNDs, this delay in diagnosis is inevitable. Understanding the genetic basis of PLS might help in reducing the time from the onset of symptoms to diagnosis, and it will improve our understanding of the disease biology favouring the development of a treatment.

The aim of our study is to collect a large international PLS genetic and clinical dataset to investigate its genetic and phenotypic landscapes as well as to evaluate whether genetic testing should be advised in PLS. Through Project MinE and AnswerALS, we accessed whole-genome sequencing data of 120 PLS, 7405 ALS and 2444 controls. We identified variants in several MND genes such asFIG4, FUS, SPG7, SPG11andSQSTM1genes among others and repeat expansions in theATXN1(12.2%) andNIPA1(7.3%) genes, but none in theC9orf72andATXN2genes. Overall PLS patients harboured fewer clinically actionable MND-associated variants than ALS patients (p = 0.0001), however, depending on the panel, up to 11% of people with PLS might benefit from genetic testing. By looking at the clinical characteristics of these cohorts, the age of symptom onset was not younger for people with PLS than for those with ALS in both Project MinE and AnswerALS. On such bases, we advise that the current diagnostic criteria that discourage the use of genetic testing and rely on age of onset should be reconsidered.
Molecular diagnosis of Cytomegalovirus infection: clinical performance of Transcription Mediated Amplification (TMA) towards conventional qPCR chemistry on whole blood samples
Authors: Bottino Paolo , Pastrone Lisa , Zanotto Elisa , Sidoti Francesca , Costa Cristina , Cavallo Rossana
Published: July 2023

Human Cytomegalovirus (HCMV) infection represents a life-threating pathogen for immunocompromised patients. Molecular quantitative testing on whole blood or plasma represents the gold standard for diagnosis of invasive HCMV infection and for monitoring antiviral treatment in individuals at risk of CMV disease. For these reasons, accurate standardization towards the 1st WHO International standard between different centres and diagnostic kits represent an effort for a better clinical management of CMV-positive patients. Herein, we evaluate for the first time the performance of a new TMA (Transcription Mediated Amplification) kit towards qPCR chemistry, used as routine method, on whole blood samples. 755 clinical whole blood specimens were collected and simultaneously tested with TMA and qPCR assays. Data showed 99.27% agreement for positive quantified samples and 89.39% agreement for those not detected between two tested methods. Evaluation of viraemia in positive samples highlighted a good correlation for TMA and qPCR chemistries in terms of International Units (ΔLog10IU/ml: − 0.29 ± 0.40). TMA assay showed a significant correlation with qPCR also in monitored patients until three months, thus allowing accurate evaluation of viraemia in transplanted patients. Moreover, preliminary data about analytical sensitivity of TMA chemistry onto DBS samples showed 86.54% correlation with whole blood specimens. Thus, TMA chemistry showed a good agreement with qPCR assay, used as current diagnostic routine, and offers important advantages: FDA and IVD approval on plasma and whole blood, automated workflow with minimal hands-on time, random access loading, thus enabling a rapid and reliable diagnostics in HCMV-infected patients.
Effects of a clinical decision support system and patient portal for preventing medication-related falls in older fallers: Protocol of a cluster randomized controlled trial with embedded process and economic evaluations (ADFICE_IT)
Authors: de Wildt Kelly K. , van de Loo Bob , Linn Annemiek J. , Medlock Stephanie K. , Groos Sara S. , Ploegmakers Kim J. , Seppala Lotta J. , Bosmans Judith E. , Abu-Hanna Ameen , van Weert Julia C.M. , van Schoor Natasja M. , van der Velde Nathalie
Published: July 2023

Background

Falls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs.

Methods

A multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient’s consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression.

Discussion

The findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries.

Trial registration

ClinicalTrials.govNCT05449470(7-7-2022)

Participant recruitment

7 July 2022-ongoing *

* Results of this study have not yet been published or submitted to any journal.

Protocol version

1

Trial sponsor

Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam