bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining the stable coexistence of drug-resistant and -susceptible pathogens: the Resistance Acquisition Purifying Selection model
Authors: Pennings Pleuni S
Published: December 2023

Drug resistance is a problem in many pathogens. While overall, levels of resistance have risen in recent decades, there are many examples where after an initial rise, levels of resistance have stabilized. The stable coexistence of resistance and susceptibility has proven hard to explain – in most evolutionary models, either resistance or susceptibility ultimately “wins” and takes over the population. Here, we show that a simple stochastic model, mathematically akin to mutation-selection balance theory, can explain several key observations about drug resistance: (1) the stable coexistence of resistant and susceptible strains (2) at levels that depend on population-level drug usage and (3) with resistance often due to many different strains (resistance is present on many different genetic backgrounds). The model works for resistance due to both mutations or horizontal gene transfer (HGT). It predicts that new resistant strains should continuously appear (through mutation or HGT and positive selection within treated hosts) and disappear (due to a fitness cost of resistance). The result is that while resistance is stable,whichstrains carry resistance is constantly changing. We used data from a longitudinal genomic study onE. coliin Norway to test this prediction for resistance to five different drugs and found that, consistent with the model, most resistant strains indeed disappear quickly after they appear in the dataset. Having a model that explains the dynamics of drug resistance will allow us to plan science-backed interventions to reduce the burden of drug resistance.

Graphical abstract
Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons
Authors: Ott Carolyn M. , Constable Sandii , Nguyen Tri M. , White Kevin , Lee Wei-Chung Allen , Lippincott-Schwartz Jennifer , Mukhopadhyay Saikat
Published: December 2023

Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While essential during early developmental stages, the fate of granule cell cilia is unknown. Here, we provide nanoscopic resolution of ciliary dynamicsin situby studying developmental changes in granule cell cilia using large-scale electron microscopy volumes and immunostaining of mouse cerebella. We found that many granule cell primary cilia were intracellular and concealed from the external environment. Cilia were disassembed in differentiating granule cell neurons in a process we call cilia deconstruction that was distinct from pre-mitotic cilia resorption in proliferating progenitors. In differentiating granule cells, ciliary loss involved unique disassembly intermediates, and, as maturation progressed, mother centriolar docking at the plasma membrane. Cilia did not reform from the docked centrioles, rather, in adult mice granule cell neurons remained unciliated. Many neurons in other brain regions require cilia to regulate function and connectivity. In contrast, our results show that granule cell progenitors had concealed cilia that underwent deconstruction potentially to prevent mitogenic hedgehog responsiveness. The ciliary deconstruction mechanism we describe could be paradigmatic of cilia removal during differentiation in other tissues.
Healthcare Cost Literacy: Exploration of Concept and Initial Development of a Novel Tool in a Representative U.S. Adult Population
Authors: Guttentag Alexandra , Warraich Haider J , van Meijgaard Jeroen
Published: December 2023

There is a growing need for understanding and addressing the issue of healthcare cost literacy (HCL) in the United States. We conducted a survey in partnership with YouGov targeting a representative sample of 1500 American adults (median age 47, 51.4% female, 62.8% white) to help develop a novel tool to assess the prevalence of HCL, and to estimate levels of HCL and health literacy across various sociodemographic and health-related variables. An exploratory factor analysis revealed that the HCL questions mapped to three factors: 1) knowledge on health insurance terminology/interpretation, 2) ability to estimate healthcare costs ahead of time, and 3) confidence in performing cost comparisons between healthcare plans and deductibles. An understanding of Americans’ levels of HCL will help policymakers and various stakeholders in the healthcare system to develop targeted plans to educate consumers on financial planning and evaluation in the healthcare system.
Association of Daily Step Count and Postoperative Surgical Complications Among All of Us Research Participants
Authors: Gehl Carson J. , Verhagen Nathaniel B. , Shaik Tahseen J. , Nimmer Kaitlyn , Yang Xin , Xing Yun , Taylor Bradley W. , Nataliansyah Mochamad M. , Kerns Sarah L. , Kothari Anai N.
Published: December 2023

Background

The association between preoperative wearable device step counts and surgical outcomes has not been examined using commercial devices linked to electronic health records (EHR). This study measured the association between daily preoperative step counts and postoperative complications.

Study Design

Data was obtained using the All of Us (AOU) Research program, a nationwide initiative to collect EHR and health-related data from the population. Included were patients who underwent a surgical procedure included in the National Surgical Quality Improvement Program (NSQIP) targeted procedures dataset. Excluded were patients who did not have available physical activity FitBit data. Primary outcome was the development of a postoperative complication. All analyses were performed in the AOU researcher workbench.

Results

Of 27,150 patients who underwent a surgical procedure, 475 participants with preoperative wearable data were included. 74.7% were female and 85.2% were White. The average age was 57.2 years. The overall rate of postoperative complications was 12.6%. Patients averaging fewer than 7,500 daily steps were at increased odds for developing a postoperative complication (OR 1.83, 95% CI [1.01, 3.31]). Following adjustment for age, sex, race, comorbid disease, body mass index (BMI), and relative procedure risk, patients with a baseline average steps/day < 7,500 were at increased odds for postoperative complication (aOR = 2.06, 95% CI [1.05, 4.06]).

Conclusions

This study found an increase in overall postoperative complication rate in patients recording lower average preoperative step counts. Patients with a baseline of less than 7,500 steps per day had increased odds of postoperative complications in this cohort. This data supports the use of wearable devices for surgical risk stratification and suggests step count may measure preoperative fitness.
Clinical features of cystic neutrophil granulomatous mastitis in 62 cases
Authors: Wang Mengjie , Zhang Dongxiao , Fu Na , Liu Min , Zhang Hongkai , Feng Shuo , Zeng Yifei , Zhao Wenjie , Cui Jianchun , Mansoor Khattak Mazher
Published: December 2023

Background

Cystic Neutrophilic Granulomatous Mastitis (CNGM) is a rare inflammatory condition affecting the breast. Despite its rarity, understanding its pathogenesis and clinical features is crucial for accurate diagnosis and effective management. This study delves into the nuanced aspects of CNGM, shedding light on its unique characteristics and potential underlying mechanisms. Methods: In this meticulous investigation, we meticulously examined and analyzed the biological data, clinical features, ultrasound imaging findings, and histopathological morphological information of 62 patients diagnosed with CNGM after thorough pathological examination. The study cohort was sourced from the Galactophore department of Beijing Hospital of Traditional Chinese Medicine, spanning the period from September 2019 to September 2022. Results: Sixty-two patients, with an average age of 33.30 years, were predominantly female. Among the 52 patients with detailed documentation of onset following the final delivery, various factors were identified, including hyperprolactinemia, pituitary tumors, psychiatric medication history, granulomatous mastitis history, breast trauma history, and a family history of breast cancer. The primary clinical manifestations were characterized by pain and palpable masses, accompanied by localized symptoms such as redness, ulceration, nipple discharge, and nipple retraction. Additionally, systemic symptoms, such as fever, headache, erythema nodosum, and cough, were observed. Ultrasound examinations revealed predominantly hypoechoic masses with heterogeneous echogenicity. Axillary lymphadenopathy, dilated ducts, and thickening of breast tissue were also noted in some cases. Histopathological analyses demonstrated lobular structural destruction, acute and chronic inflammatory cell infiltration, multinucleated giant cell reactions, granulomas, and cyst formation. Gram staining revealed detection rates of 41.94% (26/62) for gram-positive bacteria and 11.29% (7/62) for gram-negative bacteria. Conclusion: This study highlights the occurrence of Chronic Nonspecific Granulomatous Mastitis (CNGM) in women of childbearing age. Factors such as milk stasis, mammary duct secretion overcharge, exogenous trauma, hormonal influences, and bacterial colonization are implicated in the initiation and recurrence of CNGM. Notably, nipple retraction emerged not only as a clinical symptom but also as a potential risk factor for CNGM. The prevalence of multiple hypoechoic regions in CNGM surpassed that observed in breast cancer cases. The detection of gram-positive bacteria underscores the pivotal role of bacterial infections in the development of CNGM.
Expression of mechano-growth factor (MGF) in refractory overactive bladder
Authors: Spiritosanto E , Lemmon B , Mohamedi-Yousufi F , Munasinghe HA , Mahmood A , Bray R , McNeice R , Mackenzie FE , Hill NJ , Cortes E
Published: December 2023

Overactive bladder (OAB) is a urological symptom complex defined by urinary urgency. It can have a devastating impact on an individual’s quality of life and leads to significant financial cost. Insulin-like growth factor 1 (IGF-1) is a protein hormone involved in a broad range of processes including cell proliferation and differentiation. IGF-1 is also regulated through alternative splicing. While the primaryIGF-1Eatranscript is highly expressed in liver, the alternativeIGF-1Ectranscript encodes the proteolytically-derived MGF peptide and has been primarily studied in skeletal muscle. MGF has been shown to stimulate satellite cell proliferation following tissue mechanical stretch or injury, but the role of MGF in smooth muscle, such as the detrusor muscle of the bladder, has been little explored. The aim of this study was to explore the expression of MGF in bladder biopsies from patients with OAB and age-matched controls.

We show using immunohistochemistry that MGF is widely expressed in bladder tissue. Quantification of MGF expression by western blot showed that average MGF expression is more than doubled in OAB biopsies compared to controls (mean MGF in OAB=0.51±0.1, n=23; mean MGF in controls=0.22±0.07, n=9; p=0.05). Furthermore, there is an inverse correlation between MGF protein levels and symptom severity, as determined by the urodynamic parameter maximum cystometric capacity (correlation=0.53, p=0.03 n=16). MGF expression was highest in OAB biopsies with strong expression of the muscle cell markerDES. Combined with our observation that MGF induces cell proliferation in primary bladder cultures, our data suggests that high MGF expression in OAB patients may represent an attempted protective response in the bladder.
The association between the gut microbiome and 24-hour blood pressure measurements in the SCAPIS study
Authors: Lin Yi-Ting , Sayols-Baixeras Sergi , Baldanzi Gabriel , Dekkers Koen F. , Hammar Ulf , Nguyen Diem , Nielsen Nynne , Eklund Aron C. , Varotsis Georgios , Holm Jacob B. , Nielsen H. Bjørn , Lind Lars , Bergström Göran , Smith J. Gustav , Engström Gunnar , Ärnlöv Johan , Sundström Johan , Orho-Melander Marju , Fall Tove
Published: December 2023

Background and Aims

Large population-based studies on gut microbiota and hypertension have been conducted using methods with low taxonomic resolution and office blood pressure. This study aims to investigate the relationship between specific characteristics of the gut microbiome and 24-hour blood pressure measurements.

Methods and results

The association of gut microbial species, determined by shotgun metagenomic sequencing of fecal samples, with 24-hour ambulatory blood pressure measurements was assessed in 4063 participants without antihypertensive medication from the Swedish CArdioPulmonary bioImage Study. Multivariable-adjusted models identified 140 microbial species associated with at least one of the 24-hour blood pressure traits. Notably,Roseburia faecis,R. inulinivorans, andDorea longicatenawere strongly positively associated with mean systolic and diastolic blood pressure, whileAlistipes communisandA. shahiiwere inversely associated with diastolic blood pressure. An enrichment of threonine degradation I,Bifidobacteriumshunt, and lactate production was observed in species associated with mean systolic and diastolic blood pressure. Species positively associated with blood pressure were in general also positively associated with secondary bile acids but negatively associated with primary bile acids and vitamin A-related metabolites.

Conclusions

In this large cross-sectional analysis, we identified a group of gut microbial species and microbial functions associated with blood pressure. Our findings provide insights into the relation of the gut microbiome and blood pressure, which can lead to a new understanding of the etiology of hypertension.
COVID-19 vaccine effectiveness among South Asians in Ontario: A test-negative design population-based case-control study
Authors: Chanchlani Rahul , Shah Baiju R. , Bangdiwala Shrikant I. , de Souza Russ , Luo Jin , Bolotin Shelly , Bowdish Dawn ME , Desai Dipika , Lear Scott A , Loeb Mark , Punthakee Zubin , Sherifali Diana , Wahi Gita , Anand Sonia S.
Published: December 2023

Objectives

To: 1) evaluate the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians, and 2) compare the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians.

Design

Test negative design study

Setting

Ontario, Canada between Dec 14, 2020 and Nov 15, 2021

Participants

All eligible individuals >18 years with symptoms of COVID-19 and subdivided by South Asian ethnicity versus other, and those who were vaccinated versus non-vaccinated.

Main Outcome measures

The primary outcome was vaccine effectiveness as defined by COVID-19 infections, hospitalizations, and deaths, and secondary outcome was the odds of COVID-19 infections, hospitalizations, and death comparing non-vaccinated South Asians to non-vaccinated non-South Asians.

Results

883,155 individuals were included. Among South Asians, two doses of COVID-19 vaccine prevented 93.8% (95% CI 93.2, 94.4) of COVID-19 infections and 97.5% (95% CI 95.2, 98.6) of hospitalizations and deaths. Among non-South Asians, vaccines prevented 86.6% (CI 86.3, 86.9) of COVID-19 infections and 93.1% (CI 92.2, 93.8) of hospitalizations and deaths. Non-vaccinated South Asians had higher odds of symptomatic SARS-CoV-2 infection compared to non-vaccinated non-South Asians (OR 2.35, 95% CI 2.3, 2.4), regardless of their immigration status.

Conclusions

COVID-19 vaccines are effective in preventing infections, hospitalizations and deaths among South Asians living in Canada. The observation that non-vaccinated South Asians have higher odds of symptomatic COVID-19 infection warrants further investigation.

What is already known?

Some ethnic communities, such as South Asians, were disproportionately impacted during the COVID-19 pandemic. However, there are limited data on COVID-19 vaccine efficacy among this high-risk ethnic group.

What this study adds?

-

In this large population-based study including close to 900,000 individuals in Canada, we show COVID-19 vaccines are effective in preventing symptomatic SARS CoV-2 infections, hospitalizations and deaths among both South Asians and non-South Asians.

-

We also demonstrate that, among non-vaccinated individuals, South Asians have higher odds of COVID-19 infection, and an increased risk of COVID-19 hospitalizations and deaths compared to non-South Asians.
A survey of UK nurses about their care of people with malignant fungating wounds
Authors: Pramod Susy , Dumville Jo , Norman Gill , Stringer Jacqui
Published: December 2023

Background

Malignant fungating wounds (MFW) are nonhealing wounds affecting people with advanced cancer. There is currently no research evidence on who delivers care for people’s MFW in the UK and what care these professionals deliver. This survey focussed on nurses who deliver care for people with MFW to find out more about their roles and the care they deliver, and to explore perceived barriers and facilitators to delivering care for these wounds.

Method

An online anonymous survey was conducted among nurses who provide wound care for people with MFW across the UK. Study data were collected using Qualtrics XM software and analysed with SPSS.

Result

We received 154 questionnaire responses. Respondents were tissue viability nurses, community nurses and other specialist nurses. The main reported MFW-related management aims were to manage wound odour, exudate, pain and bleeding, and prevention of infection. The top-ranked treatment aim was pain management followed by odour management. The most reported antimicrobial dressing was topical silver, and the non-antimicrobial dressing was superabsorbent. Access to MFW care training is reported as a barrier to providing care to people with MFW as is a lack of local and national guidelines. Availability of dressings, access to training, and good communication processes were reported as facilitators.

Conclusion

This is the first study that explored MFW wound care practices in the UK. A range of nurses are involved in care delivery with variations in the treatments used. Lack of access to MFW care training, resources, and standardised guidelines may impede care delivery.
What’s On the Menu? Towards Predicting Nutritional Quality of Food Environments
Authors: Seo DongHyeon , Horn Abigail , Abeliuk Andrés , Burghardt Keith
Published: December 2023

Unhealthy diets are a leading cause of major chronic diseases including obesity, diabetes, cancer, and heart disease. Food environments–the physical spaces in which people access and consume food–have the potential to profoundly impact diet and related diseases. We take a step towards better understanding the nutritional quality of food environments by developing MINT: Menu Item to NutrienT model. This model utilizes under-studied data sources on recipes and generic food items, along with state-of-the-art word embedding and deep learning methods, to predict the nutrient density of never-before-seen food items using only their name as input. The model achieves anR2= 0.77, a sub-stantial improvement over comparable models. We illustrate the utility of MINT by applying it to the Los Angeles restaurant food environment, and discover close agreement between predicted and ground truth nutrient density of restaurant menu items. This model represents a significant step towards a policy toolkit needed to precisely identify and target food environments characterized by poor nutritional quality.
Alterations in Resting-State Functional Connectivity and Dynamics in Schizophrenia as a Result of Global not Local Processes
Authors: Metzner Christoph , Dimulescu Cristiana , Kamp Fabian , Fromm Sophie , Uhlhaas Peter J , Obermayer Klaus
Published: December 2023

We examined changes in large-scale functional connectivity and temporal dynamics and their underlying mechanisms in schizophrenia (ScZ) through measurements of resting-state functional magnetic resonance imaging (rs-fMRI) data and computational modelling. The rs-fMRI measurements from patients with chronic ScZ (n=38) and matched healthy controls (n=43), were obtained through the public schizConnect repository. Computational models were constructed based on diffusion-weighted MRI scans and fit to the experimental rs-fMRI data. We found decreased large-scale functional connectivity across sensory and association areas and for all functional subnetworks for the ScZ group. Additionally global synchrony was reduced in patients while metastability was unaltered. Perturbations of the computational model revealed that decreased global coupling and increased background noise levels both explained the experimentally found deficits better than local changes to the GABAergic or glutamatergic system. The current study suggests that large-scale alterations in ScZ are more likely the result of global rather than local network changes.
Reengineering a machine learning phenotype to adapt to the changing COVID-19 landscape: A study from the N3C and RECOVER consortia
Authors: Crosskey Miles , McIntee Tomas , Preiss Sandy , Brannock Daniel , Yoo Yun Jae , Hadley Emily , Blancero Frank , Chew Rob , Loomba Johanna , Bhatia Abhishek , Chute Christopher G. , Haendel Melissa , Moffitt Richard , Pfaff Emily
Published: December 2023

Background

In 2021, we used the National COVID Cohort Collaborative (N3C) as part of the NIH RECOVER Initiative to develop a machine learning (ML) pipeline to identify patients with a high probability of having post-acute sequelae of SARS-CoV-2 infection (PASC), or Long COVID. However, the increased home testing, missing documentation, and reinfections that characterize the latter years of the pandemic necessitate reengineering our original model to account for these changes in the COVID-19 research landscape.

Methods

Our updated XGBoost model gathers data for each patient in overlapping 100-day periods that progress through time, and issues a probability of Long COVID for each 100-day period. If a patient has known acute COVID-19 during any 100-day window (including reinfections), we censor the data from 7 days prior to the diagnosis/positive test date through 28 days after. These fixed time windows replace the prior model’s reliance on a documented COVID-19 index date to anchor its data collection, and are able to account for reinfections.

Results

The updated model achieves an area under the receiver operating characteristic curve of 0.90. Precision and recall can be adjusted according to a given use case, depending on whether greater sensitivity or specificity is warranted.

Discussion

By eschewing the COVID-19 index date as an anchor point for analysis, we are now able to assess the probability of Long COVID among patients who may have tested at home, or with suspected (but untested) cases of COVID-19, or multiple SARS-CoV-2 reinfections. We view this exercise as a model for maintaining and updating any ML pipeline used for clinical research and operations.
Multi-phase, multi-ethnic GWAS uncovers putative loci in predisposition to human sprint performance, health and disease
Authors: Wang Guan , Fuku Noriyuki , Miyamoto-Mikami Eri , Tanaka Masashi , Miyachi Motohiko , Murakami Haruka , Cheng Yu-Ching , Mitchell Braxton D. , Morrison Errol , Austin Krista G. , Ahmetov Ildus I. ,   Sportgene Research Group, Generozov Edward V. , Filipenko Maxim L. , Gilep Andrei A. , Gineviciene Valentina , Moran Colin N. , Venckunas Tomas , Cieszczyk Pawel , Derave Wim , Papadimitriou Ioannis , Garton Fleur C. , North Kathryn , Padmanabhan Sandosh , Pitsiladis Yannis P.
Published: December 2023

The genetic underpinnings of elite sprint performance remain largely elusive. For the first time, we uncovered rs10196189 (GALNT13) in the cross-ancestry, genome-wide analysis of elite sprint and power-oriented athletes and their controls from Jamaica, the USA, and Japan, and replicated this finding in two independent cohorts of elite European athletes (meta-analysisP< 5E-08). We identified statistically significant and borderline associations for cross-ancestry and ancestry specific loci inGALNT13,BOP1,HSF1,STXBP2 GRM7,MPRIP,ZFYVE28, CERS4, andADAMTS18, predominantly expressed in the nervous and hematopoietic systems. Further, we revealed thirty-six previously uncharacterized genes associated with host defence, leukocyte migration, and cellular responses to interferon-gamma and unveiled (reprioritized) four genes,UQCRFS1,PTPN6,RALYandZMYM4,responsible for aging, neurological conditions, and blood disorders from the elite athletic performance cohorts. Our results provide new biological insights into elite sprint performance and offer clues to the potential molecular mechanisms interlinking and operating in elite athletic performance and human health and disease.
Larger social networks may increase stigma against vocal illness: An integrated empirical and computational study of deciphering help-seeking behaviors and vocal stigma
Authors: Glick Aaron R. , Jones Colin , Martignetti Lisa , Blanchette Lisa , Tova Theresa , Henderson Allen , Pell Marc D. , Li-Jessen Nicole Y. K.
Published: December 2023

Background

Individuals with a stigmatized medical condition are often reluctant to seek medical help. Among professionals, singers and actors often experience stigma associated with voice disorders. Scientific evidence for vocal stigma is, however, limited and primarily anecdotal. No quantitative research has explored the impact that vocal stigma may have on help-seeking behavior in professional vocal performers. This study deployed and integrated empirical and computational tools to (1) quantify the experience of vocal stigma and help-seeking behaviors and (2) predict their modulations with peer influences in social networks.

Methods

Experience of vocal stigma and information-motivation-behavioral (IMB) skills were prospectively profiled using online surveys from a total of 403 Canadians (200 vocal performers and 203 controls). The survey data were used to formulate an agent-based network model that numerically simulates the effect of social interactions on vocal stigma and help-seeking behaviors. Each virtual agent updates their IMB states via social interaction, which in turn changes their self- and social-stigma states. Profiles from vocal performers and non-vocal performers were compared as a function of network size. Network analysis was performed to evaluate the effect of social network structure on the flow of information and motivation among virtual agents.

Results

Over 4000 simulation runs in each context, larger social networks are more likely to contribute to an increase in vocal stigma. For small social networks, total stigma was reduced with higher total IMB but much less so for large networks with around 400 agents. For the agent population of vocal performers with high social-stigma and risk for voice disorder, their vocal stigma is resistant to large changes in IMB. Agents with extreme IMB and stigma values are also likely to polarize their networks faster in larger social groups.

Conclusions

We used empirical surveys to contextualize vocal stigma and IMB in real world populations and developed a computational model to theorize and quantify the interaction among stigma, health-seeking behavior and influence of social interactions. This work establishes an effective, predictable experimental platform to provide scientific evidence in developing public policy or social interventions of reducing health stigma in voice disorders and other medical conditions.
Prevalence, risks and outcomes of frailty in People Experiencing Homelessness: a protocol for secondary analysis of Health Needs Audit data
Authors: Dawes Jo , Walters Kate , Frost Rachael , Bagkeris Emmanouil , Burton Alexandra , Herzberg Debra , Hayward Andrew
Published: December 2023

Frailty describes a health state related to ageing where people become less resilient to health challenges and more likely to have adverse outcomes if they become unwell. People experiencing homelessness (PEH) are known to have poor health, with research suggesting that many become frail at a younger age than the general population. Previous research using small-scale primary data collection suggests that the prevalence of frailty in homeless populations varies widely (16-55%), with variations in sample sizes and settings partially accounting for differences in current estimates. The prevalence, risks, and outcomes of frailty in PEH are poorly understood. We propose to carry out a secondary analysis of existing health survey data collected from 2,792 PEH. This will involve creating a Frailty Index (FI) to identify frail people within the dataset. Regression analyses will be used to identify associations between potential risk factors and outcomes of frailty in this population. This protocol will: 1) Outline the creation of a FI to assess the frailty prevalence within a dataset of health information collected from a cohort of PEH and 2) Describe proposed methods of regression analysis for identification of associations between frailty and risks factors/outcomes of frailty in the cohort of PEH within the dataset. The processes described in this paper can inform future development of FIs in other datasets. It is expected that the FI created will be an appropriate and robust method for identifying frailty in a cohort of PEH and results of the secondary data analysis will provide a more robust estimate of the associations between frailty and risk factors/outcomes.
Spatial and Temporal Patterns of SARS-CoV-2 transmission in uMgungundlovu, Kwa-Zulu Natal, South Africa
Authors: Gangat Radiya , Ngah Veranyuy , Tawonga Rushambwa , Blanford Justine I. , Ncayiyana Jabulani Ronnie , Nyasulu Peter Suwirakwenda
Published: December 2023

Background

Investigating the spatial distribution of SARS-CoV-2 at a local level and describing the pattern of disease occurrence can be used as the basis for efficient prevention and control measures. This research project aims to utilize geospatial analysis to understand the distribution patterns of SARS-CoV-2 and its relationship with certain co-existing factors.

Methods

Spatial characteristics of SARS-CoV-2 were investigated over the first four waves of transmission using ESRI ArcGISPro v2.0, including Local Indicators of Spatial Association (LISA) with Moran’s “I” as the measure of spatial autocorrelation; and Kernel Density Estimation (KDE). In implementing temporal analysis, time series analysis using the Python Seaborn library was used, with separate modelling carried out for each wave.

Results

Statistically significant SARS-CoV-2 incidences were noted across age groups with p-values consistently < 0.001. The central region of the district experienced a higher level of clusters indicated by the LISA (Moran’s I: wave 1 – 0.22, wave 2 – 0.2, wave 3 – 0.11, wave 4 – 0.13) and the KDE (Highest density of cases: wave 1: 25.1-50, wave 2: 101-150, wave 3: 101-150, wave 4: 50.1-100). Temporal analysis showed more fluctuation at the beginning of each wave with less fluctuation in identified cases within the middle to end of each wave.

Conclusion

A Geospatial approach of analysing infectious disease transmission is proposed to guide control efforts (e.g., testing/tracing and vaccine rollout) for populations at higher vulnerability. Additionally, the nature and configuration of the social and built environment may be associated with increased transmission. However, locally specific empirical research is required to assess other relevant factors associated with increased transmission.
Optimal and Safe Pain Management Approach in Ankle and Hindfoot Fractures: Improving Practitioner Decision
Authors: Ahmad Tashfeen , Muhammad Zehra Abdul , Mohib Yasir , Hussain Riaz , Umer Masood
Published: December 2023

Background

Over or sub-optimal analgesic treatment leads to undesired consequences and patient dissatisfaction. The study aims to assess the sub-optimal or optimal pain relief and safety of routinely prescribed oral analgesic(s) at discharge and 1-week post-discharge in ankle and foot fracture surgeries.

Methods

The ongoing prospective cohort study data on 54 ankle and hindfoot trauma fracture adult patients enrolled between June 2022 to July 2023 was analyzed. Post-surgery oral analgesics prescribed at hospital discharge and 1-week follow-up were stratified for assessing adverse events and pain (Visual Analogue Scale) at 1- and 2 weeks post-discharge. The relationship of age, gender, and comorbidity was analyzed by multiple logistic regression for adverse events and multiple linear regression for pain score.

Results

Median pain scores at 1- and 2-week follow-ups were 3.2 (IQR=3.0) and 2 (IQR=2.0) respectively. Combinations of tramadol, acetaminophen with naproxen or diclofenac or orphenadrine; and naproxen, pregabalin, with acetaminophen seemed toxic with sub-optimal pain control. Similar results were for celecoxib combined with pregabalin and etoricoxib combined with diclofenac or tramadol. Acetaminophen alone was safe but occasionally showed intolerance. Etoricoxib or diclofenac alone or with acetaminophen was safe and showed better pain control in this cohort. A regression model was non-significant for a relationship between covariates and pain scores or adverse events.

Conclusion

Current data suggests that certain oral analgesics or their combinations are harmful with sub-optimal pain control while some are safe and effective. Choosing suitable analgesics or their combinations in specific fractures might reduce patient harm with optimal pain management.
Use of a Single Case-Finding Questionnaire to Simultaneously Target Multiple Related Diseases Allows Enhanced Disease Detection
Authors: Aaron Shawn D. , Huynh Chau , Whitmore George Alex
Published: December 2023

Objective

To develop a research methodology to apply a single case-finding tool to multiple related diseases and to evaluate the ability of a single tool to detect two or more related chronic diseases.

Methods

Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialing. Multiple risk scores, one for asthma and one for COPD, were developed using data from a single case-finding questionnaire administered to the study population. Each score was statistically optimized for targeted detection of cases having one disease in the class. External validation of tandem risk scores was prospectively conducted in an independent sample and predictive performance re-evaluated.

Results

Sensitivity for detection of asthma improved from 87% using single risk scores to 96% using tandem risk scores, and sensitivity for detection of COPD similarly improved from 87% to 99%. In the independent validation cohort, case-finding sensitivities increased from 64% and 59% using single risk scores to 95% and 96% using tandem risk scores for asthma and for COPD, respectively.

Conclusions

Use of a single questionnaire which incorporates risk scores for multiple diseases considered in tandem, rather than individually, enhances the yield of cases detected when compared with one-at-a-time application of risk scores for case discovery. Benefits include greater efficiency in case-finding and improved sensitivities for detection of each disease.

What is New?

We describe case finding in a population of undiagnosed, symptomatic subjects who have one disease from a class of related chronic diseases.

Multiple risk scores are developed using data from a single case-finding instrument administered to a representative sample from the study population. Each score is statistically optimized for targeted detection of cases having one disease in the class.

Use of multiple risk scores, when considered in tandem, enhances the yield of cases detected when compared with one-at-a-time application of risk scores for case discovery.
LOW LEVELS OF DIRECT ORAL ANTICOAGULANTS AT STEADY STATE IN ATRIAL FIBRILLATION PATIENTS WHO LATER DEVELOP THROMBOTIC COMPLICATIONS; THE PROSPECTIVE MAS (MEASURE AND SEE) STUDY
Authors: Testa Sophie , Palareti Gualtiero , Legnani Cristina , Dellanoce Claudia , Cini Michela , Paoletti Oriana , Ciampa Antonio , Antonucci Emilia , Poli Daniela , Morandini Rossella , Tala Maurizio , Chiarugi Paolo , Santoro Rita Carlotta , Iannone Angela Maria , Candia Erica De , Pignatelli Pasquale , Faioni Elena Maria , Chistolini Antonio , Esteban Maria del Pilar , Marietta Marco , Tripodi Armando , Tosetto Alberto ,   MAS Study group
Published: December 2023

Background

Though effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve the efficacy of treatment is an open issue.

Methods

We carried out the observational, prospective, multicenter study [“Measure and See” Study (MAS) (NCT03803579)]. Blood was collected 15-30 days after starting DOAC treatment in AF patients, who were then followed for one year. Plasma samples were centralized, for DOAC levels measurement. Patients’ DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values by subtracting from the original values the overall mean value of each DOAC and divided by the standard deviation. Standardized values represent the distance of each value from the overall mean.

Results

Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. Twenty-one thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% patient/years). 17/21 thrombotic events occurred in patients whose standardized activity levels were below the mean of each DOAC (zero); the incidence was the highest (4.08% patient/years) in patients whose standardized values were in the lowest class (below zero, σ; - 1.00).

Conclusions

Early measurement of DOAC levels in AF patients allowed us to identify most of the subjects who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated.
Somatic mutation as an explanation for epigenetic aging
Authors: Koch Zane , Li Adam , Evans Daniel S. , Cummings Steven , Ideker Trey
Published: December 2023

DNA methylation marks have recently been used to build models known as “epigenetic clocks” which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In analysis of multimodal data from 9,331 human individuals, we find that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but also with pervasive remodeling of the methylome out to ±10 kilobases. This one-to-many mapping enables mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging faster or slower than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age. These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life.
Exploring white matter dynamics and morphology through interactive numerical phantoms: The White Matter Generator
Authors: Winther S. , Peulicke O. , Andersson M. , Kjer H. M. , Bærentzen J. A. , Dyrby T. B.
Published: December 2023

Brain white matter is a dynamic environment that continuously adapts and reorganizes in response to stimuli and pathological changes. Glial cells, especially, play a key role in tissue repair, inflammation modulation, and neural recovery. The movements of glial cells and changes in their concentrations can influence the surrounding axon morphology. We introduce the White Matter Generator (WMG) tool to enable the study of how axon morphology is influenced through such dynamical processes, and how this, in turn, influences the diffusion-weighted MRI signal. This is made possible by allowing interactive changes to the configuration of the phantom generation throughout the optimisation process. The phantoms can consist of axons, myelinated axons, and cell clusters, separated by extra-cellular space. Due to morphological flexibility and computational advantages during the optimisation, the tool uses ellipsoids as building blocks for all structures; chains of ellipsoids for axons, and individual ellipsoids for cell clusters. After optimisation, the ellipsoid representation can be converted to a mesh representation which can be employed in Monte-Carlo diffusion simulations. This offers an effective method for evaluating tissue microstructure models for diffusion-weighted MRI in controlled realistic white matter environments. Hence, the WMG offers valuable insights into white matter’s adaptive nature and implications for diffusion-weighted MRI microstructure models, and thereby holds the potential to advance clinical diagnosis, treatment, and rehabilitation strategies for various neurological disorders and injuries.
Cortical tracking of postural sways during standing balance.
Authors: Legrand Thomas , Mongold Scott J , Muller Laure , Naeije Gilles , Vander Ghinst Marc , Bourguignon Mathieu
Published: December 2023

Maintaining an upright stance requires the integration of sensory inputs from the visual, vestibular and somatosensory-proprioceptive systems by the cortex to develop a corrective postural strategy. However, it is unclear whether and how the cerebral cortex monitors and controls postural sways. Here, we asked whether postural sways are encoded in ongoing cortical oscillations, giving rise to a form of corticokinematic coherence (CKC) in the context of standing balance. Center-of-pressure (CoP) and center of mass (CoM) fluctuations and electroencephalographic cortical activity were recorded as young healthy participants performed balance tasks during which sensory information was manipulated, by either removal or alteration. We found that postural sways are represented in ongoing SM1 cortical activity during challenging balance conditions, in the form of CKC at 1-6 Hz that was stronger for CoP compared with CoM fluctuations. Time delays between cortical activity and CoP features indicated that both afferent and efferent pathways contribute to CKC, wherein the brain would monitor the CoP velocity and control its position. Importantly, CKC was behaviorally relevant, as it predicted the increase in instability brought by alteration of sensory information. Our results demonstrate that human sensorimotor cortical areas take part in the closed-loop control of standing balance in challenging conditions. They demonstrate that CKC could serve as a neurophysiological marker of cortical involvement in maintaining balance.
Virological characteristics of the SARS-CoV-2 JN.1 variant
Authors: Kaku Yu , Okumura Kaho , Padilla-Blanco Miguel , Kosugi Yusuke , Uriu Keiya , Hinay Alfredo A , Chen Luo , Plianchaisuk Arnon , Kobiyama Kouji , Ishii Ken J ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Zahradnik Jiri , Ito Jumpei , Sato Kei
Published: December 2023

The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the currently circulating SARS-CoV-2 Omicron XBB lineages, including EG.5.1 and HK.3. Comparing to XBB and BA.2, BA.2.86 carries more than 30 mutations in the spike (S) protein, indicating a high potential for immune evasion. BA.2.86 has evolved and its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbors S:L455S and three mutations in non-S proteins. S:L455S is a hallmark mutation of JN.1: we have recently shown that HK.3 and other “FLip” variants carry S:L455F, which contributes to increased transmissibility and immune escape ability compared to the parental EG.5.1 variant. Here, we investigated the virological properties of JN.1.
Effects of urbanisation, habitat characteristics, and management on garden pond biodiversity: findings from a large-scale citizen science survey
Authors: Márton Zsuzsanna , Barta Barbara , Vad Csaba F. , Szabó Beáta , Hamer Andrew J. , Kardos Vivien , Laskai Csilla , Fierpasz Ádám , Horváth Zsófia
Published: December 2023

The rapid expansion of urban areas often leads to degradation, fragmentation, and loss of natural habitats, threatening biodiversity. While urban ponds might contribute substantially to the biodiversity of urban blue-green infrastructure, the role of garden ponds is still largely unkown. We lack a comprehensive understanding of how local habitat features, different forms of management, and urbanisation might impact the biodiversity of these habitats. This study aimed to reveal the importance of garden ponds via a country-wide online citizen science survey in Hungary, Central Europe. Data from over 800 pond owners revealed the occurrence and local frequency of various native animal taxa (amphibians, odonates, and birds), and introduced animals (e.g., fish). We collected data about pond features and management practices. We tested the effect of pond features, pond management, and landscape-level drivers (urbanisation, surrounding wetland coverage) on the presence of conspicuous animal taxa (adult amphibians and tadpoles, birds, odonates) to identify the potential drivers of the biodiversity of garden ponds. Key pond features including pond age, area, aquatic and shoreline vegetation were the most important factors, while algaecide addition was the most influential management practice negatively affecting amphibian presence. Urbanisation negatively affected the presence of adult amphibians and their tadpoles, but it was not associated negatively with the presence of odonates and birds. Our results indicate the high potential to utilise garden ponds as urban habitats surveyed with the help of the public. Developing effective urban biodiversity monitoring and conservation strategies are necessary for a better functioning blue-green infrastructure. The high level of engagement of pond owners, as in our survey, can create valuable data for achieving these aims.