bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of cooperation in the unidirectional linear division of labour of finite roles
Authors: Nirjhor Md Sams Afif , Nakamaru Mayuko
Published: March 2023

Evolution of cooperation is a puzzle in evolutionary biology and social sciences. Previous studies assumed that players are equal and have symmetric relationships. In our society, players are in different roles, have an asymmetric relationship and cooperate together. We focused on the linear division of labour in a unidirectional chain that has finite roles, each of which is assigned to one group with cooperators and defectors. A cooperator in an upstream group produces and modifies a product, paying a cost of cooperation, and hands it to a player in a downstream group who obtains the benefit from the product. If players in all roles cooperate, a final product can be completed. However, if a player in a group chooses defection, the division of labour stops, the final product cannot be completed and all players in all roles suffer damage. By using the replicator equations of the asymmetric game, we investigate which sanction system promotes the evolution of cooperation in the division of labour. We find that not the benefit of the product but the cost of cooperation matters to the evolutionary dynamics and that the probability of finding a defector determines which sanction system promotes the evolution of cooperation.
Sediment reworking of intertidal sediments by the benthic foraminifera
Haynesina germanica
: the importance of motion behaviour and densities
Authors: Deldicq Noémie , Mermillod-Blondin Florian , Bouchet Vincent M. P.
Published: March 2023

This study aimed to describe for the first time the vertical motion behaviour of the intertidal foraminifera
Haynesina germanica
and its contribution to bioturbation. Its infaunal behaviour leads to the creation of a one-end tube within the first centimetre of sediment. In addition, a vertical trail following behaviour was described for the first time in foraminifera, which may be linked to the sustainability of the biogenic sedimentary structures. As a consequence,
H. germanica
produces a vertical transport of both mud and fine sediment fractions similarly to the sediment reworking mode reported for gallery-diffusor benthic species. This finding allows us to refine the bioturbating mode of
H. germanica
, previously classified as surficial biodiffusor. Furthermore, sediment reworking intensity appeared to be dependent on the foraminiferal density.
H. germanica
would adapt its motion behaviour to deal with the intra-specific competition for food and space that may occur when density increases. Consequently, this behavioural modification would affect both the species and the individual contribution to sediment reworking processes.
In fine
, sediment reworking in
H. germanica
may further contribute to the bioirrigation of intertidal sediments, which has implications for oxygen availability in sediments and on aerobic microbial processes involved in carbon and nutrient cycling at the sediment–water interface.
Respiratory Bacterial coinfections and their antibiotic resistance pattern in COVID-19 Patients at a Tertiary Care Center in India
Authors: Kar Mitra , Siddiqui Tasneem , Dubey Akanksha , Hashim Zia , Sahu Chinmoy , Ghoshal Ujjala
Published: March 2023

Introduction: Patients suffering from Coronavirus disease-2019 (COVID-19) are prone to develop respiratory bacterial infections irrespective of their need for mechanical ventilatory support.
Hypothesis/Gap Statement: Information about the incidence of concomitant respiratory bacterial infections in COVID- 19 patients from India is limited.
Aim: This study denotes the incidence of concomitant respiratory bacterial pathogens and their drug resistance in these patients.
Methodology: A prospective study was performed by including the patients who were admitted to our tertiary care center from March 2021 to May 2021 to evaluate secondary bacterial respiratory co-infections in patients with Real-time polymerase chain reaction (RT-PCR) confirmed cases of COVID-19 disease caused by SARS CoV-2 virus.
Results: Sixty-nine culture-positive respiratory samples from patients suffering from COVID-19 were incorporated into this study. The most commonly isolated bacterial microorganism was Klebsiella pneumoniae (23, 33.33%) and Acinetobacter baumannii (15, 21.73%), followed by Pseudomonas aeruginosa (13, 18.84%). Among the microorganisms isolated, 41 (59.4%) were multidrug-resistant (MDR), and 9 (13%) were extensively drug-resistant (XDR). Among the Gram-negative bacteria isolated, Klebsiella pneumoniae showed high drug resistance. Fifty carbapenem-resistant microorganisms were isolated from the patients included in our study. Concerning the hospital stay of the patients enrolled, there was an increased length of intensive care unit (ICU) stay, which was 22.25 ± 15.42 days among patients needing mechanical ventilation in comparison to 5.39 ± 9.57 days of intensive care unit stay in patients on ambient air or low/high flow oxygen.
Conclusion: COVID-19 patients need increased length of hospitalization and have a high incidence of secondary respiratory bacterial infections and high anti-microbial drug resistance.
Shiga toxin-producing Escherichia coli (STEC) and atypical enteropathogenic E. coli (aEPEC) in Swedish retail wheat flour
Authors: Soderlund Robert , Flink Catarina , Aspán Anna , Eriksson Erik
Published: March 2023

Wheat flour has been identified as the source of multiple outbreaks of gastrointestinal disease caused by shiga-toxin producing Escherichia coli (STEC). We have investigated the presence and genomic characteristics of STEC and related atypical enteropathogenic E. coli (aEPEC) in 200 bags of Swedish-produced retail wheat flour, representing 87 products and 25 brands. Samples were enriched in modified TSB and screened with real-time PCR targeting stx1, stx2, eae, and the serogroups O157, O121, and O26. Isolation was performed by IMS for suspected STEC/aEPEC O157, O121 and O26, and by screening pools of colonies for other STEC. Real-time PCR after enrichment revealed 12% of samples to be positive for shiga toxin genes (stx1 and/or stx2) and 11% to be positive for intimin (eae). Organic production, small-scale production or whole grain did not significantly influence shiga toxin gene presence or absence in a generalized linear mixed model analysis. Eight isolates of STEC were recovered, all of which were intimin negative. Multiple serotype/sequence type/shiga-toxin subtype combinations were recovered which have also been found in flour samples in other European countries. Most STEC types recovered were associated with sporadic cases of STEC among humans in Sweden, but no types known to have caused outbreaks or severe cases of disease (i.e. haemolytic-uraemic syndrome) were found. The most common finding was O187:H28 ST200 with stx2g, with possible links to cervid hosts. Wildlife associated with crop damage is a plausible explanation for at least some of the surprisingly high frequency of STEC in wheat flour.
Using an Artificial Intelligence Application Expedited ENRICH Trial Patient Screening: A Single Center Experience
Authors: C. Field Nicholas , Rogers Aubrey , Custozzo Amanda J. , Boulos Alan S. , Dalfino John , Paul Alexandra R.
Published: March 2023

Objective

The ENRICH Trial was the first to demonstrate superiority of surgical intervention over medical management when performed within 24 hours of symptom onset for supratentorial lobar hemorrhages. We aimed to determine whether the implementation of an intracranial hemorrhage detection algorithm that provides immediate active notification to provider cell phones would expediate the screening of hemorrhagic stroke patients for the trial at our institution.

Methods

A retrospective review of our prospectively collected ENRICH Trial patient screening log was performed at our Comprehensive Stroke Center. The log encompassed patients screened for the ENRICH Trial who presented between January 2018 and March 2022. Trial screening data was compared pre- and post-implementation of the VizAI (Viz.ai, San Francisco, California, USA) smartphone application.

Results

188 adult patients were identified during the study period. Time between CT Head and notification of the neurosurgical team for trial screening was reduced by 50 minutes after the implementation of VizAI (p<0.002). The number increases to 57 minutes when hemorrhages not identified by the ICH algorithm were excluded.

Conclusions

Active notification of the neurosurgical team by an artificial intelligence application significantly reduces the time from hemorrhage identification to trial screening. Further studies are needed to evaluate whether this results in a clinical benefit.
Clinical hypoxemia score for outpatient child pneumonia care lacking pulse oximetry in Africa and South Asia
Authors: Schuh Holly B. , Hooli Shubhada , Ahmed Salahuddin , King Carina , Roy Arunangshu D. , Lufesi Norman , Islam ASMD Ashraful , Mvalo Tisungane , Chowdhury Nabidul H. , Ginsburg Amy Sarah , Colbourn Tim , Checkley William , Baqui Abdullah H. , McCollum Eric D.
Published: March 2023

Background

Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia.

Methods

This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO2<93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO. Results: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO2<93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO2<93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO2<93% cases. Both LASSO models had similar performance for a SpO2<90%.

Conclusions

In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed.
Does ChatGPT Provide Appropriate and Equitable Medical Advice?: A Vignette-Based, Clinical Evaluation Across Care Contexts
Authors: Nastasi Anthony J. , Courtright Katherine R. , Halpern Scott D. , Weissman Gary E.
Published: March 2023

ChatGPT is a large language model trained on text corpora and reinforced with human supervision. Because ChatGPT can provide human-like responses to complex questions, it could become an easily accessible source of medical advice for patients. However, its ability to answer medical questions appropriately and equitably remains unknown. We presented ChatGPT with 96 advice-seeking vignettes that varied across clinical contexts, medical histories, and social characteristics. We analyzed responses for clinical appropriateness by concordance with guidelines, recommendation type, and consideration of social factors. Ninety-three (97%) responses were appropriate and did not explicitly violate clinical guidelines. Recommendations in response to advice-seeking questions were completely absent (N=34, 35%), general (N=18, 18%), or specific (N=44, 46%). Fifty-three (55%) explicitly considered social factors like race or insurance status, which in some cases changed clinical recommendations. ChatGPT consistently provided background information in response to medical questions but did not reliably offer appropriate and personalized medical advice.
US Life Expectancy Rebounds in 2022
Authors: Wetzler Harry
Published: March 2023

From 2019 to 2021 life expectancy at birth in the United States (US) declined by approximately 2.45 years to values not seen since 1996. Complete life tables for 2019 to 2022 were constructed for the total US population, females, and males using mortality data from the CDC WONDER Multiple Cause of Death database and Census Bureau Vintage population estimates. Life expectancy at birth increased by 1.07 years between 2021 and 2022. Nearly 40% of lost life expectancy years at birth were regained in 2022.
The relationship between mental health, sleep quality, and the immunogenicity of COVID-19 vaccinations
Authors: Wagenhäuser Isabell , Reusch Julia , Gabel Alexander , Mees Juliane , Nyawale Helmut , Frey Anna , Lâm Thiên-Trí , Schubert-Unkmeir Alexandra , Dölken Lars , Kurzai Oliver , Frantz Stefan , Petri Nils , Krone Manuel , Krone Lukas B.
Published: March 2023

Sleep modulates the immune response and sleep loss can reduce the immunogenicity of certain vaccinations. Vice versa immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality.

The prospective CoVacSer study monitored mental health, sleep quality, and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1,082 healthcare workers from the 29thof September 2021 to the 19thof December 2022. Questionnaires and blood samples were collected before, 14 days, and three months after the third COVID-19 vaccination. In 154 participants the assessments were also conducted before and 14 days after the fourth COVID-19 vaccination.

Healthcare workers with psychiatric disorders had slightly lower Anti-SARS-CoV-2-Spike IgG levels before the third COVID-19 vaccination. However, this effect was mediated by higher median age and body mass index in this subgroup. Antibody titres following the third and fourth COVID-19 vaccination (‘booster vaccinations’) were not significantly different between subgroups with and without psychiatric disorders. Sleep quality did not affect the humoral immunogenicity of the COVID-19 vaccinations. Moreover, the COVID-19 vaccinations did not impact self-reported sleep quality.

Our data suggests that in a working population neither mental health nor sleep quality relevantly impact the immunogenicity of COVID-19 vaccinations and that COVID-19 vaccinations are not a precipitating factor for insomnia. The findings from this large-scale real-life cohort study will inform clinical practice regarding the recommendation of COVID-19 booster vaccination for individuals with mental health and sleep problems.
The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2
Authors: Stoddard Madison , Yuan Lin , Sarkar Sharanya , Van Egeren Debra , White Laura F. , Chakravarty Arijit
Published: March 2023

In the fourth year of the COVID-19 pandemic, public health authorities worldwide have adopted a strategy of learning to live with SARS-CoV-2. This has involved the removal of measures for limiting viral spread, resulting in a large burden of recurrent SARS-CoV-2 infections. Crucial for managing this burden is the concept of the so-called wall of hybrid immunity, through repeated reinfections and vaccine boosters, to reduce the risk of severe disease and death. Protection against both infection and severe disease is provided by the induction of neutralizing antibodies (nAbs) against SARS-CoV-2. However, pharmacokinetic (PK) waning and rapid viral evolution both degrade nAb binding titers. The recent emergence of variants with strongly immune evasive potential against both the vaccinal and natural immune responses raises the question of whether the wall of population-level immunity can be maintained in the face of large jumps in nAb binding potency. Here we use an agent-based simulation to address this question. Our findings suggest large jumps in viral evolution may cause failure of population immunity resulting in sudden increases in mortality. As a rise in mortality will only become apparent in the weeks following a wave of disease, reactive public health strategies will not be able to provide meaningful risk mitigation. Learning to live with the virus could thus lead to large death tolls with very little warning. Our work points to the importance of proactive management strategies for the ongoing pandemic, and to the need for multifactorial approaches to COVID-19 disease control.
Improving the representativeness of UK’s national COVID-19 Infection Survey through spatio-temporal regression and post-stratification
Authors: Pouwels Koen B. , Eyre David W. , House Thomas , Aspey Ben , Matthews Philippa C. , Stoesser Nicole , Newton John N. , Diamond Ian , Studley Ruth , H.Taylor Nick G. , Bell John I. , Farrar Jeremy , Kolenchery Jaison , Marsden Brian D. , Hoosdally Sarah , Jones E. Yvonne , Stuart David I. , Crook Derrick W. , Peto Tim E. A. , Walker A Sarah ,   the COVID-19 Infection Survey Team
Published: March 2023

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we use spatio-temporal regression and post-stratification models to UK’s national COVID-19 Infection Survey (CIS) to obtain representative estimates of PCR positivity (6,496,052 tests) and antibody prevalence (1,941,333 tests) for different regions, ages and ethnicities (7-December-2020 to 4-May-2022). Not accounting for vaccination status through post-stratification led to small underestimation of PCR positivity, but more substantial overestimations of antibody levels in the population (up to 21%), particularly in groups with low vaccine uptake in the general population. There was marked variation in the relative contribution of different areas and age-groups to each wave. Future analyses of infectious disease surveys should take into account major drivers of outcomes of interest that may also influence participation, with vaccination being an important factor to consider.
Is the Patient State Index Recorded with the Sedline Sedation Monitor Correlated with the Duration of Emergence After Pediatric Surgery: An Exploratory, Single-center, Blinded, Prospective Cohort Study
Authors: Mitrev Ludmil , Pasch Stuart , Brotman Ian , Gourkanti Bharathi , Habib Fatima , Schwartz Michael , van Helmond Noud
Published: March 2023

Introduction

Following surgery with general anesthesia, some children experience a prolonged emergence. We designed a prospective observational study in children undergoing general anesthesia who were monitored with the SedLine®Sedation Monitoring system (Masimo Corporation, Irvine, CA) to explore the hypothesis that the Patient State Index (PSI) obtained with this monitor could be inversely correlated with the duration of emergence after anesthesia.

Materials and methods

Prospective, observational single center study in a tertiary academic center in the United States. Fifty-six children between the ages of 1 and 12 years scheduled to undergo non-emergent surgery with general inhalational anesthesia were enrolled. Demographic and intraoperative characteristics were recorded. All caregivers were blinded to the PSI. Correlations were derived between PSI, duration of emergence, post-anesthesia care unit length of stay (LOS), and hospital LOS. PSI was analyzed in categories of <25, 25-50, and >50 both as absolute time spent in each category, and as the fraction of time compared to the length of the anesthetic. The development of emergence delirium (ED) was recorded as a secondary outcome variable.

Results

The correlation coefficients between the PSI categories and the outcomes were weak (<0.3). Only two of the correlation coefficients reached statistical significance at p=0.05: fraction and absolute time spent in PSI category > 50 and PACU length of stay, indicating that longer periods of PSI > 50 during the anesthetic were associated with longer PACU LOS. Three patients (5%) developed ED.

Conclusion

PSI measured with the SedLine monitor was not significantly correlated with the duration of emergence. There was a weak positive correlation between intraoperative time spent with PSI readings >50 and PACU LOS. Our sample did not have a high-enough event rate of ED to make statistical inferences about a correlation between PSI, ED and duration of emergence.
Imaging the effects of tumour necrosis factor inhibition on pain processing in severe rheumatoid arthritis
Authors: Wartolowska Karolina , Jenkinson Mark , Andersson Jesper , Wordsworth B. Paul , Tracey Irene
Published: March 2023

Background

Monoclonal antibodies against tumour necrosis factor (TNF) markedly reduce inflammation and disease activity in rheumatoid arthritis; however, the mechanisms through which they affect pain are not fully understood.

Aims

The aim of this study was to investigate how monoclonal antibodies against TNF alter pain processing and to determine whether neuroimaging can be used as a marker of treatment efficacy and a predictor of treatment response.

Methods

Functional magnetic resonance imaging was used to study the neural correlates of clinically-relevant pain evoked by pressing the most painful joint of the right hand and experimental pain evoked by a thermal stimulus applied to the right forearm. A flashing checkerboard was used as a control stimulus. Patients with severe rheumatoid arthritis, qualifying for the anti-TNF treatment, were scanned before the beginning of the therapy and then approximately one and six months after the first injection.

Results

TNF inhibition was associated with a marked reduction in pain ratings, inflammation, disease activity as well as depression and catastrophising scores. Effective treatment was linked with less pressure-evoked brain activation in the regions involved in the processing of the sensory aspect of pain and in the limbic structures. Baseline pressure-evoked activation in the thalamus predicted future response to treatment. There was no reduction in heat-evoked brain activation; on the contrary, there was an increase in the activation in the precuneus, which is involved in interoception. There were no differences in response to the visual stimulus.

Conclusions

TNF inhibition strongly reduces brain activation in response to clinically relevant pressure pain but not experimental heat pain and these changes reflect the decrease of nociceptive input from the periphery due to the reduction of inflammation as well as central changes in pain modulation. Neuroimaging methods have the potential to explain and predict treatment effects in inflammatory pain conditions.
Influence of liver attenuation on the severity of course COVID-19: a retrospective cohort study
Authors: Shumskaya Yuliya F. , Gonchar Anna P. , Mnatsakanyan Marina G. , Blokhin Ivan A. , Reshetnikov Roman V. , Vasilev Yuriy A.
Published: March 2023

Introduction

There is no unequivocal opinion concerning the influence of decreased liver attenuation on the COVID-19 severity, but its widespread occurrence among these patients has been shown. It is still debatable whether decreased liver attenuation is an independent risk factor for the severe course of CVID-19.

Study objective

To assess the prognostic value of liver attenuation on CT scan in patients with COVID-19.

Material and methods

A retrospective cohort study. Data of COVID-19 outpatients were analyzed. Inclusion criteria: two chest CT scans, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood, and polymerase chain reaction results to verify SARS-CoV-2. Subjects were categorized into four comparison groups depending on the severity of lung involvement. Liver attenuation was analyzed by automatic segmentation, where the values less than 40 HU were considered pathological.

Results

Data from 499 subjects were included. The groups differed in age and the level of liver attenuation on both CT scans. No correlation between ALT, AST and changes in liver attenuation was found. On follow-up CT, low liver attenuation was observed in males (odds ratio (OR) 2.79 (95% CI 1.42–5.47),p-value= 0.003) and in patients with a baseline reduced liver attenuation (OR 60.59 (95% CI 30.51–120.33),p-value< 0.001). Age over 60 years was associated with the development of lung lesions (OR 1.04 (95% CI 1.02–1.06) for extent of lung injury < 25%, OR 1.08 (95% CI 1.05–1.11) for 25–50%, OR 1.1 (95% CI 1.06–1.15) for 25– 50%,p-value< 0.001). Low liver attenuation on the baseline CT scan increased the odds of severe lung injury (OR 6.9 (95% CI 2.06–23.07),p-value= 0.002).

Conclusion

In COVID-19, patients with low liver attenuation are more likely to develop severe lung damage.
Pointing in the right direction: Motor improvements with directional versus circular DBS
Authors: Hurt Christopher P , Kuhman Daniel J , Guthrie Barton L , Olson Joseph W , Nakhmani Arie , Wade Melissa , Walker Harrison C
Published: March 2023

Directional brain stimulation provides greater control of radial current spread than conventional ring-shaped electrodes. Whether this added flexibility can improve motor function is unclear. Here we examine whether directional and circular stimulation differentially change motor performance in patients with Parkinson’s disease. We measured motor behaviors in 31 patients who underwent unilateral subthalamic nucleus brain stimulation surgery (SUNDIAL,NCT03353688) from each of 8 configurations (6 directional contacts and their corresponding rings) during device activation. Objective measures of dexterity, gait, balance, and overall mobility were queried in a double-blind fashion in the practically defined “off” medication state versus preoperative baseline with stimulus amplitude at the center of the therapeutic window. The best versus the worst directional contact on a given row yields significant changes in performance across 5 motor tasks (p<0.001 each task). Specific stimulation directions can worsen function versus baseline, whereas the best direction yields greater improvement than ring stimulation (p=0.005, p=0.001, p=0.007, p<0.001, respectively, across tasks). Although directional DBS improves side effect thresholds versus ring stimulation (p<0.001), the side effect threshold and therapeutic window correlate only modestly with motor improvements. Resting beta power did not predict motor improvements by directional DBS across any of the motor tasks. Optimized directional subthalamic nucleus DBS yields better group-level motor performance than ring stimulation, in addition to known advantages related to tolerability. Prospective studies should evaluate whether these improvements persist over longer time intervals.
Quantification of Subtype Purity in Luminal A Breast Cancer Predicts Clinical Characteristics and Survival
Authors: Kumar Neeraj , Gann Peter H. , McGregor Stephanie M. , Sethi Amit
Published: March 2023

Purpose

PAM50 profiling assigns each breast cancer to a single intrinsic subtype based on a bulk tissue sample. However, individual cancers may show evidence of admixture with an alternate subtype that could affect prognosis and treatment response. We developed a method to model subtype admixture using semi-supervised non-negative matrix factorization (ssNMF) of whole transcriptome data and associated it with tumor, molecular, and survival characteristics for Luminal A (LumA) samples.

Methods

We combined TCGA and METABRIC cohorts and obtained transcriptome, molecular, and clinical data, which yielded 11,379 gene transcripts in common, and 1,179 cases assigned to LumA. We used ssNMF to compute the subtype admixture proportions of the four major subtypes – pLumA, pLumB, pHER2 and pBasal – for each case and measured associations with tumor characteristics, molecular features, and survival.

Results

Luminal A cases with low pLumA transcriptomic proportion were likelier to have non-luminal pathology, higher clinical and genomic risk factors, and lower overall survival (log rankP< 10−5), independent of age, stage, and tumor size. We found positive associations between pHER2 and HER2-positivity by IHC or FISH; between pLumB and PR negativity; and between pBasal and younger age, node positivity,TP53mutation, and EGFR expression. Predominant basal admixture, in contrast to predominant LumB or HER2 admixture, was not associated with shorter survival.

Conclusions

Bulk sampling for genomic analyses provides an opportunity to expose intratumor heterogeneity, as reflected by subtype admixture. Our results elucidate the striking extent of diversity among LumA cancers and suggest that determining the extent and type of admixture holds promise for refining individualized therapy. LumA cancers with a high degree of basal admixture appear to have distinct biological characterstics that warrant further study.
Maternal characteristics and pregnancy outcomes during the global pandemic Covid-19 in indonesian tertiary referral hospital
Authors: Farizi Sofia Al , Setyowati Dewi , Azyanti Azra Fauziyah , Fatmaningrum Dyah Ayu , Candrakirana Rahayu Kusuma
Published: March 2023

Aim

Analyse differences in intervention and pregnancy outcomes characteristics in obstetric patients with a diagnosis of COVID-19 and non-COVID-19 at one of the Indonesia tertiary referral hospital in East Java.

Design

This was cross sectional study.

Methods

This study was performed 694 obstetric patients, the data for these patients were obtained from the hospital medical records Sampling was used simple random. This study used Mann-Whitney test to analyse the differences between the variables.

Results

There was a significant difference in the Length Of Stay (LOS), LOS of COVID-19 patients tends to be longer than that of non-COVID-19 patients. More than half of the patients gave birth by caesarean delivery, 83 for COVID-19 and 283 for Non COVID-19. Some of the most common complications among COVID-19 patients were maternal infectious and parasitic diseases (1.3% vs 0.0%), abnormalities of forces of labour (12.3% vs 9.6%), complication of puerperium (0.6 % vs 0.0%). 40.9% COVID-19 patient suffered Acute Respiratory Distress Syndrome (ARDS). COVID-19 infection had no significant effect on pregnancy outcomes.

Conclusion

Several interventions need to be re-evaluated, such as cesarean delivery in COVID-19 and non-COVID-19 patients. The health-care delivery system must also be re-evaluated, and the tiered referral system must be strengthened.
Metagenome-assembled microbial genomes from Parkinson’s disease fecal samples
Authors: Duru Ilhan Cem , Lecomte Alexandre , Shishido Tânia Keiko , Laine Pia , Suppula Joni , Paulin Lars , Scheperjans Filip , Pereira Pedro A. B. , Auvinen Petri
Published: March 2023

The human gut microbiome composition has been linked to Parkinson’s disease (PD). However, knowledge of the gut microbiota on the genome level is still limited. Here we performed deep metagenomic sequencing and binning to build metagenome-assembled genomes (MAG) from 136 human fecal microbiomes (68 PD samples and 68 control samples). We constructed 952 non-redundant high-quality MAGs and compared them between PD and control groups. Among these MAGs, there were 22 different versions ofCollinsellaandPrevotellaMAGs, indicating high variability of those genera in the human gut environment. Microdiversity analysis indicated thatRuminococcus bromiiwas statistically significantly (p < 0.002) more diverse on the strain level in the control samples compared to the PD samples. In addition, by clustering all genes and performing presence-absence analysis between groups, we identified several control-specific (p < 0.05) related genes, such asspeFand Fe-S oxidoreductase. We also report detailed annotation of MAGs, including Clusters of Orthologous Genes (COG), Cas operon type, antiviral gene, prophage, and secondary metabolites biosynthetic gene clusters, which can be useful for providing a reference for future studies.
Comparison of hemodynamic response functions obtained from resting-state functional MRI and invasive electrophysiological recordings in rats
Authors: Rangaprakash D , David Olivier , Barry Robert L , Deshpande Gopikrishna
Published: March 2023

Resting-state functional MRI (rs-fMRI) is a popular technology that has enriched our understanding of brain and spinal cord functioning, including how different regions communicate (connectivity). But fMRI is an indirect measure of neural activity capturing blood hemodynamics. The hemodynamic response function (HRF) interfaces between the unmeasured neural activity and measured fMRI time series. The HRF is variable across brain regions and individuals, and is modulated by non-neural factors. Ignoring this HRF variability causes errors in FC estimates. Hence, it is crucial to reliably estimate the HRF from rs-fMRI data. Robust techniques have emerged to estimate the HRF from fMRI time series. Although such techniques have been validated non-invasively using simulated and empirical fMRI data, thorough invasive validation using simultaneous electrophysiological recordings, the gold standard, has been elusive. This report addresses this gap in the literature by comparing HRFs derived from invasive intracranial electroencephalogram recordings with HRFs estimated from simultaneously acquired fMRI data in six epileptic rats. We found that the HRF shape parameters (HRF amplitude, latency and width) were not significantly different (p>0.05) between ground truth and estimated HRFs. In the single pathological region, the HRF width was marginally significantly different (p=0.03). Our study provides preliminary invasive validation for the efficacy of the HRF estimation technique in reliably estimating the HRF non-invasively from rs-fMRI data directly. This has a notable impact on rs-fMRI connectivity studies, and we recommend that HRF deconvolution be performed to minimize HRF variability and improve connectivity estimates.
Prevalence ofPlasmodium vivaxin a semi-arid region of northern Kenya
Authors: Prudhomme O’Meara Wendy , Maraga Linda , Meredith Hannah , Esimit Daniel , Lokoel Gilchrist , Chepkwony Tabitha , Kipkoech Joseph , Ambani George , Menya Diana , Freedman Elizabeth , Taylor Steve , Obala Andrew
Published: March 2023

Most malaria morbidity in Kenya is due toPlasmodium falciparumwith no cases attributed toP.vivax. Little is known about the epidemiology in northern Kenya along the border with Ethiopia and Sudan. We found that 2% of household members ofP.falciparumcases were infected withP.vivax, affecting all ages in urban and rural sites.
A one health approach for enhancing the integration ofSalmonella entericasurveillance in Colombia
Authors: Bernal Johan F. , Díaz Paula L. , Perez-Sepulveda Blanca M. , Valencia-Guerrero María Fernanda , Weisner Magdalena , Clavijo Viviana , Montaño Lucy Angeline , Arevalo Stefany A. , León Ingrid Maribel , Castellanos Luis Ricardo , Underwood Anthony , Duarte Carolina , Argimón Silvia , Moreno Jaime , Aanensen David , Donado-Godoy Pilar
Published: March 2023

Foodborne diseases represent a link between environmental, animal, and human health interfaces from the One Health perspective. Whole genome sequencing (WGS) is becoming the gold standard in foodborne surveillance, worldwide. WGS than provides precision data from pathogens allows laboratories to resolve the genetic relations among all sources from One Health perspective, especially during outbreak investigations, getting insights into their transmission routes and pathogenicity.Salmonellaspp. is the most prevalent foodborne bacteria in Colombia, in 2020, 268 foodborne outbreaks were reported to National health institute (INS) and 3079 invasive and faecal salmonellosis samples from 81% of the Colombian geographical regions. Several studies in different food sources exhibited an increase of contamination withSalmonella, a public health concern due to the steady development of antimicrobial resistance associated to specific serovars. However, integration ofSalmonella spp. data including food-chain supply and clinical interfaces is very scarce in Colombia. This study carried out a national comparison ofSalmonellaisolates collected from food-chain supply and clinical sources. Using an epidemiological and phenotypic approach, we demonstrated the higher resolution of WGS compared with PFGE, routinely used inSalmonellasurveillance in Colombia. For example, the resolution of PFGE allowed the description of two main clusters of foodSalmonellaEnteritidis isolates which were expanded to eight clades by using WGS. Virulence factors and antimicrobial determinant genes observed in the foodborne clades should be considered a public health concern in Colombia. WGS is a technology that provides precise and valid evidence for the establishment of dissemination routes of foodborne high-riskSalmonellaclades, but it requires an integrative and continued collaboration between the stakeholders across the One Health interfaces to promote and support integrated real-time actions in public health.
Anti-Correlation of KLRG1 and PD-1 Expression in Human Tumor CD8 T Cells
Authors: Greenberg Steven A
Published: March 2023

Recently, combination checkpoint therapy of cancer has been recognized as producing additive as opposed to synergistic benefit due to in part to positively correlated effects. The potential for uncorrelated or negatively correlated therapies to produce true synergistic benefits has been noted. Whereas the inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT have been collectively characterized as exhaustion receptors, another inhibitory receptor KLRG1 was historically characterized as a senescent receptor and received relatively little attention as a potential checkpoint inhibitor target. The anti-tumor effects of KLRG1 blockade has relatively recently been demonstrated in preclinical in vivo studies. Here, expression of the inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and KLRG1 was studied in publicly available gene expression datasets. Bulk RNA microarray and RNAseq, and single cell RNAseq data from healthy blood and tumor tissue samples were analyzed for Pearson correlation. CD8 T cell differentiation of memory T cells from the TEM to TEMRA states is characterized by PD-1/KLRG1 anti-correlation, with decreased PD-1 expression but increased KLRG1 expression. Single cell RNAseq analysis of tumor infiltrating CD8 T cells shows positive correlation of CTLA-4, TIM-3, LAG-3, and TIGIT with PD-1 but negative correlation of KLRG1 with PD-1. The anti-correlation of PD-1 and KLRG1 expression in human tumor infiltrating CD8 T cells suggests the potential for combination therapy supra-additive benefits of anti-PD-1 and anti-KLRG1 therapies.
Interobserver Variability in Target Definition for Stereotactic Arrhythmia Radioablation
Authors: van der Ree Martijn H. , Cuculich Phillip S. , van Herk Marcel , Hugo Geoffrey D. , Balt Jippe C. , Bates Matthew , Ho Gordon , Pruvot Etienne , Herrera-Siklody Claudia , Hoeksema Wiert F. , Lee Justin , Lloyd Michael S. , Kemme Michiel , Sacher Frederic , Tixier Romain , Balgobind Brian V. , Robinson Clifford G. , Rasch Coen R.N. , Postema Pieter G.
Published: March 2023

Background

Stereotactic arrhythmia radioablation (STAR) is emerging as a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR.

Methods

Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists (observers) delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the arrhythmogenic cardiac VT target in three patients previously treated with STAR based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed (e.g. image integration). Thirdly, observers delineated three predefined segments from the cardiac 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume as expressed by the root-mean-square of the observer standard deviation (RMS SD) over the target volume, and the Dice coefficient.

Results

Ten electrophysiologists completed the study. For the first phase (spinal canal delineation), interobserver variability was low as indicated by low variation in distance to the median volume (RMS SD range: 0.02-0.02cm) and high Dice coefficients (mean: 0.97±0.01). In the second phase (VT-target delineation), distance to the median volume was large (RMS SD range: 0.52-1.02cm) and the Dice coefficients low (mean: 0.40±0.15). In the third phase (segment delineation), similar results were observed (RMS SD range: 0.51-1.55cm, Dice coefficient mean: 0.31±0.21)

Conclusions

Interobserver variability is high for manual delineation of the VT-target and ventricular segments. Difficulties in cardiac anatomical orientation on traditional radiation oncology CT scans appear to be an important driver of variability. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation.
A Supervised Text Classification System Detects Fontan Patients in Electronic Records with Higher Accuracy than ICD Codes
Authors: Guo Y , Al-Garadi MA , Book WM , Ivey LC , Rodriguez FH , Raskind-Hood CL , Robichaux C , Sarker A
Published: March 2023

Background

The Fontan operation palliates single ventricle heart defects and is associated with significant morbidity and premature mortality. Native anatomy varies; thus, Fontan cases cannot always be identified byInternational Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM)codes, making it challenging to create large Fontan patient cohorts. We sought to develop natural language processing (NLP) based machine learning (ML) models, which utilize free text notes of patients, to automatically detect Fontan cases, and compare their performances with ICD code based classification.

Methods and Results

We included free text notes of 10,935 manually validated patients, of whom 778 (7.1%) were Fontan and 10,157 (92.9%) non-Fontan patients, from two large, diverse healthcare systems. Using 5-fold cross validation, we trained and evaluated multiple ML models, namely support vector machines (SVM) and a transformer based model for language understanding named RoBERTa (2 versions), for automatically identifying Fontan cases based on free text notes. To optimize classifier performances, we experimented with different text representation techniques, including a sliding window strategy to overcome the length limit imposed by RoBERTa. We compared the performances of the ML models to ICD code based classification using the F1score metric. The ICD classification model, SVM, and RoBERTa achieved F1scores of 0.81 (95% CI: 0.79-0.83), 0.95 (95% CI: 0.92-0.97), and 0.89 (95% CI: 0.88-0.85) for the positive (Fontan) class, respectively. SVM obtained the best performance (p<0.05), and both NLP models outperformed ICD code based classification (p<0.05). The novel sliding window strategy improved performance over the base RoBERTa model (p<0.05) but did not outperform SVM. ICD code based classification tended to have more false positives compared to both NLP models.

Conclusions

Our proposed NLP models can automatically detect Fontan patients based on clinical notes with higher accuracy than ICD codes. Since the sensitivity of ICD codes is high but the positive predictive value is low, it may be beneficial to apply ICD codes as a filter prior to applying NLP/ML to achieve optimal performance.
Approach to Machine Learning for Extraction of Real-World Data Variables from Electronic Health Records
Authors: Adamson Blythe , Waskom Michael , Blarre Auriane , Kelly Jonathan , Krismer Konstantin , Nemeth Sheila , Gippetti James , Ritten John , Harrison Katherine , Ho George , Linzmayer Robin , Bansal Tarun , Wilkinson Samuel , Amster Guy , Estola Evan , Benedum Corey M. , Fidyk Erin , Estevez Melissa , Shapiro Will , Cohen Aaron B.
Published: March 2023

Background

As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI’s ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability.

Methods

We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (eg, clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (ie, not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information.

Results

We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates.

Conclusions

NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer.
Severe haemolysis during primaquine radical cure ofPlasmodium vivaxmalaria: two systematic reviews and individual patient data descriptive analyses
Authors: Yilma Daniel , Groves Emily S , Brito-Sousa Jose Diego , Monteiro Wuelton M , Chu Cindy , Thriemer Kamala , Commons Robert J , Lacerda Marcus V G , Price Ric N , Douglas Nicholas M
Published: March 2023

Background

Primaquine (PQ) killsPlasmodium vivaxhypnozoites but can cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Methods

We did two systematic reviews: the first used data from clinical trials to determine the spectrum of definitions and frequency of haematological serious adverse events (SAE) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management and outcome of ‘severe’ PQ-associated haemolysis necessitating hospitalisation.

Findings

In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 haematological SAEs amongst 9,824 patients with vivax malaria treated with PQ, 9 of which necessitated hospitalisation or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalised following PQ radical cure; 79.9% (123/154) of whom were prescribed PQ at ≥0.5mg/kg/day. Overall, 101 patients were categorised as having probable or possible ‘severe’ PQ-associated haemolysis, 96.8% of whom were G6PD deficient (<30% activity). The first symptoms of haemolysis were mostly reported on day 2 or 3 (45.5%) and all patients were hospitalised within 7 days of PQ commencement. 57.9% (77/133) of patients had blood transfusion. Seven (6.9%) patients with probable or possible haemolysis died.

Interpretation

Even when G6PD testing is available, enhanced monitoring for haemolysis is warranted following PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of haemolysis. More robust definitions of severe PQ-associated haemolysis are required.

Funding

WHO-TDR, Australian National Health and Medical Research (NHMRC), The Bill & Melinda Gates Foundation.