bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccine coverage among immigrants and refugees in Alberta: a population-based cross-sectional study
Authors: MacDonald Shannon E. , Paudel Yuba Raj , Du Crystal
Published: April 2022

Introduction

Studies have shown that immigrants have lower vaccination rates than the Canadian-born population. We sought to assess COVID-19 vaccine coverage and factors associated with uptake among foreign-born immigrants relative to the non-immigrant population in Alberta, Canada.

Methods

In this cross-sectional study, we analyzed population-based linked administrative health data from Alberta to examine vaccine coverage for 3,931,698 Albertans, of which 731,217 were immigrants. We calculated COVID-19 vaccination coverage as the proportion of eligible Albertans with a record of receiving at least one dose of a COVID-19 vaccine as of November 29, 2021. We used multivariable logistic regression to examine the association of vaccine coverage with migration status (immigrants: four categories based on time since migration and non-immigrants) adjusting for socio-demographic variables.

Results

Overall, COVID-19 vaccination coverage was higher among immigrants (78.2%; 95% CI: 78.1%-78.3%) compared to non-immigrants (76.0%; 95% CI: 75.9%-76.0%). Coverage among immigrants differed by continent of origin, with North America, Oceania, and Europe having the lowest coverage. Although vaccine coverage was relatively uniform across neighborhood income quintiles for immigrants, immigrants living in rural areas had lower vaccine coverage compared to non-immigrants living in rural areas. Multivariable logistic regression analysis showed a significant interaction between age category and migration status. While immigrants below 50 years of age generally had significantly higher vaccine coverage compared to non-immigrants, there was some variation based on time since migration. Immigrants above 50 years of age showed significantly lower coverage compared to non-immigrants of the same age.

Conclusion

Public health interventions should focus on older immigrants, immigrants living in rural areas, and immigrants from specific continental backgrounds in order to improve COVID-19 vaccination coverage.
Investigation of the association between high arachidonic acid synthesis and colorectal polyp incidence: a Mendelian randomisation approach
Authors: Moon Rachel , Moore J. Bernadette , Hull Mark A. , Zulyniak Michael A.
Published: April 2022

Background & Aims

Arachidonic acid (ARA) is causally associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC. Therefore, this study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence using Mendelian randomisation.

Methods

Summary level GWAS data from European, Singaporean, and Chinese cohorts (n=10,171) identified 4 single nucleotide polymorphisms (SNPs) associated with blood ARA levels (p< 5 × 10−8). After pruning, 1 SNP was retained (rs174547; p=3.0×10−971) for 2-stage Mendelian randomisation to infer the causal effect of ARA on self-reported colorectal polyp outcomes within the UK Biobank (1,391 cases; 462,933 total).

Results

No association between ARA and colorectal polyp incidence was observed [OR= 1.00 (95% CI: 0.99, 1.00); P-value = 0.50).

Conclusions

Blood levels of ARA do not associate with colorectal polyp incidence. This work supports the contention that downstream lipid mediators, such as PGE2, are key for polyp formation during early-stage colorectal carcinogenesis
Discovery of Neurocognitive Phenotypes of Autism By Analyzing Functional Connectivity in the Default Mode Network and Dorsolateral Prefrontal Cortex
Authors: Vasantha Amith
Published: April 2022

Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually presenting as reduced social interaction, lessened verbal communication, and repetitive behavior. Diagnosing ASD is extremely difficult because of its wide variety of symptoms, so it can only be diagnosed through behavioral tests and analysis of developmental history. Resting-state fMRI can help researchers discover a neural substrate for ASD to diagnose it earlier. One prominent fMRI database for ASD research is the Autism Brain Imaging Data Exchange, a large-scale collection of anonymized functional MRI scans subdivided by age, gender, handedness, and scores on behavioral assessments.

This analysis focused on two brain networks: the default mode network (DMN), which is active when minds wander, and the executive network, which is active during the performance of tasks. The medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and angular gyrus are nodes of the DMN, and the dorsolateral prefrontal cortex (DLPFC) is the main node in the executive network. Both networks are affected by ASD.

This research used preprocessed resting-state fMRI data to establish neurocognitive phenotypes for ASD. Bivariate correlation was used to compare connectivity in the DMN and DLPFC between ASD and control fMRI scans, and these differences were analyzed for correlations with each patient’s assessment scores. After the Benjamini-Hochberg procedure was applied to reduce the false discovery rate, analysis of these metrics revealed that in ASD patients there was underconnectivity between the right PCC and the right mPFC, while in control patients there was overconnectivity between the right angular gyrus and left DLPFC. ASD is extremely heritable, so phenotypic research is absolutely necessary for discovering more about the genetic causes of ASD, which will speed up ASD diagnosis and help researchers develop more targeted treatments for ASD.
Morphometric and molecular analysis of Schistosomes eggs recovered from human urines in communities along the shore-line of Oyan-dam in Ogun State, Nigeria
Authors: Bayegun Adedotun Ayodeji , Omitola Olaitan Olamide , Umunnakwe Uche Cynthia , Akande Adedayo Foluke , Akinwale Olaoluwa P. , Mogaji Hammed Oladeji , Ademolu Kehinde O. , Gyang Pam Vincent , Odoemene Nnayere Simon , Ekpo Uwem Friday
Published: April 2022

Background

There are growing concerns that communities characterized with surface water, where both humans and livestock interact for agricultural, domestic, cultural, and recreational purposes, are likely to support hybridization between schistosome species infecting humans and livestock. This study therefore investigated the possible human infections with hybrid schistosomes in four schistosomiasis endemic communities along the banks of Oyan dam in Ogun State, Nigeria.

Methods

Human urine samples were collected in Imala-Odo, Abule-Titun, Apojula and Ibaro-Oyan communities. Recovered eggs were counted, photographed, and measured with IC Measure™ for Total Length, Maximum Width, and a ratio of egg shape. Eighty-seven unusual Schistosoma eggs shaped were molecularly characterised by PCR amplification of Schistosoma specific Dra1 gene. The amplicons were further subjected to PCR amplification of schistosome ITS-2 rDNA and right representative samples with varying gel band sizes were sequenced.

Results

A total of 1,984 Schistosoma eggs were analysed. The egg morphometrics were within the range of 70.90 - 262.30 μm and 30.10 - 102.60 μm for total length and width respectively. The length to width ratio was 1.60 - 4.06μm. Majority of the eggs have the typical round-to-oval shaped eggs (1345, 67.8 %), followed by eggs with atypical spindle-shaped (639, 32.2 %) and eggs without spines (22, 1.1 %). Egg morphotypes were significantly different (p = 0.017). PCR amplification of Dra1 gene and ITS2 confirmed 54 (62.1%) of the eggs and 33 (61.1%) of Schistosoma origin. Sequencing of two of the DNA samples produced sequences similar to vertebrate S. magrebowiei (accession number UZAI01000474.1) and Asian S. japonicum (accession number SKCS01001458.1).

Conclusion

These findings suggest possibly that hybrids schistosome may be circulating in the human population in the study areas.

Author summary

Human schistosomiasis is one of the most common neglected tropical diseases in Africa. The disease is caused by a water-borne trematode parasite, and transmission among human requires contact with infested water bodies. There are growing concerns that communities characterized with infested surface water, where both humans and livestock interact are likely to support hybridization between schistosome species infecting humans and livestock. We therefore screened human urine samples using morphological and molecular methods, for the presence of hybrid schistosomes in four communities along the banks of Oyan dam in Ogun State, Nigeria. Our findings show the possible occurrence of hybrid schistosomes in the study area, which call for urgent public health interventions.
Overestimation of School-Based Deworming Coverage Resulting from School-Based Reporting
Authors: Sheahan William , Anderson Roy , Aruldas Kumudha , Avokpaho Euripide , Galagan Sean , Goodman Jeanne , Houngbegnon Parfait , Israel Gideon John , Janagaraj Venkateshprabhu , Kaliappan Saravanakumar Puthupalayam , Means Arianna Rubin , Morozoff Chloe , Pearman Emily , Ramesh Rohan Michael , Roll Amy , Schaefer Alex , Ajjampur Sitara S. R. , Bailey Robin , Ibikounlé Moudachirou , Kalua Khumbo , Luty Adrian J.F. , Pullan Rachel , Walson Judd L. , Ásbjörnsdóttir Kristjana Hrönn
Published: April 2022

Background

Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD.

Methodology/Principal Findings

Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected.

In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi.

Conclusions/Significance

These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities.
Aging in India: Comparison of Conventional and Prospective Measures, 2011
Authors: Srivastava Ankita , Nandita Saikia
Published: April 2022

Conventional measurements of aging do not take into account the dynamic nature of aging-related characteristics over time. Therefore, in order to refine the estimates of aging, demographers have proposed prospective measures based on remaining life expectancy, Sanderson and Scherbov (2007). We compared these new measures with conventional aging measures using the data from the Census of India 2011 and Sample Registration System life tables 2009–2013. In conventional aging measures, we used life expectancy at age 60 and the old age dependency ratio (OADR), whereas for new measures of aging, we applied the threshold of old age based on the remaining life expectancy and prospective old age dependency ratio (POADR). Both measures of aging provided different estimates of the aging population at the national and subnational levels. At national level, application of prospective measures increased the number of older dependents from 66.4 million to 71.8 million (OADR: 8.6% vs. POADR: 10.6%). We observed profound variation at sub-national level in India. We also observed that the prospective ageing measures not only provided higher estimates of ageing burden in India, but also altered the gender and rural urban differential in ageing. Considering the heterogeneity of life expectancies across Indian states, prospective measures provide more accurate refined estimates of aging burden in India as they are based on length of life expectancy. Application of these measures has great policy relevance in India.
SYSTEMATIC REVIEW EXPLORING THE IMPACT OF SOCIO-CULTURAL FACTORS ON PAIN MANAGEMENT APPROACHES IN SUB- SAHARAN AFRICA
Authors: Dompreh Henrietta Obaabeng , Lynch Mary , Longworth Mary
Published: April 2022

Aim

The experience and expression of pain are influenced by numerous factors of which culture and the society plays a major role especially in SSA. However, few studies have focused on the impact of cultural influences on pain assessment and management in SSA. This systemic review examines pain prevalence and its intensity/severity, the socio-cultural factors that affect pain management and the extent to which socio-cultural practices influence pain assessment and management in SSA.

Methods

Applying the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted. Seven electronic databases were searched, and a strict inclusion and exclusion criteria applied to the retrieve articles along with a robust filtering to identify eligible peer reviewed literature. The review process concluded with 24 eligible articles and following the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was applied to assess the quality of the included literature and thematic narrative analysis was conducted.

Results

The analysis findings identified that there are sociocultural barriers to effective pain management from the perspective of different subcultures in SSA. The evidence suggests that religious/spiritual and inherited beliefs, along with limited knowledge and health literacy influence the experience and pain management approaches applied in SSA. In addition, results indicate that, resource constraints and cultural and societal norms impact on access and use of pain management among the population in SSA.

Conclusion

Healthcare professionals should be aware of how the society, cultural and beliefs of their patients influence their expression of pain and subsequent pain management. Under-treatment or over-treatment might occur if health workers are unaware or do not consider the cultural norms associated with pain and pain expression, due to the subjective and individual nature of pain.
Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis
Authors: Wu Xiaoling , Cao Shaobo , Yu Bo , He Tao
Published: April 2022

Background

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious.

Objectives

We aim to review and analyze literature on the efficacy and safety of DOACs compared to VKAs in treating patients with APS. A literature search was performed from inception to March 1, 2022. Subgroups were analyzed based on the risk stratification of APS profiles and different DOAC types.

Results

A total of 9 studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis (RR=3.65, 95% CI:1.49-8.93; I2=29%, P=0.005) compared to those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR=2.63; 95% CI, 1.56-4.42; I2 =0, P=0.0003), particularly recurrent arterial thromboses (RR=4.52; 95% CI, 1.99-10.29; I2 =0, P=0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences.

Conclusions

In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.
Prioritisation of Informed Health Choices (IHC) Key Concepts to be included in lower-secondary school resources: a consensus study
Authors: Agaba Joseph Jude , Chesire Faith , Michael Mugisha , Nandi Pamela , Njue Jane , Nsangi Allen , Nsengimana Venuste , Oyuga Cyril , Rutiyomba Florian , Semakula Daniel , Ssenyonga Ronald , Uwimana Innocent , Oxman Andrew D
Published: April 2022

Background

The Informed Health Choices Key Concepts are principles for thinking critically about healthcare claims and deciding what to do. The Key Concepts provide a framework for designing curricula, learning resources, and evaluation tools.

Objectives

To prioritise which of the 49 Key Concepts to include in resources for lower-secondary schools in East Africa.

Methods

Twelve judges used an iterative process to reach a consensus. The judges were curriculum specialists, teachers, and researchers from Kenya, Uganda, and Rwanda. After familiarising themselves with the concepts, they pilot tested draft criteria for selecting and ordering the concepts. After agreeing on the criteria, nine judges independently assessed all 49 concepts and reached an initial consensus. We sought feedback on the draft consensus from teachers and other stakeholders. After considering the feedback, nine judges independently reassessed the prioritised concepts and reached a consensus. The final set of concepts was determined after user-testing prototypes and pilot-testing the resources.

Results

The first panel prioritised 29 concepts. Based on feedback from teachers, students, curriculum developers, and other members of the research team, two concepts were dropped. A second panel of nine judges prioritised 17 of the 27 concepts. Due to the Covid-19 pandemic and school closures, we have only been able to develop one set of resources instead of two, as originally planned. Based on feedback on prototypes of lessons and pilot-testing a set of 10 lessons, we determined that it was possible to introduce nine concepts in 10 single-period (40 minute) lessons. We included eight of the 17 prioritised concepts and one additional concept.

Conclusion

Using an iterative process with explicit criteria, we prioritised nine concepts as a starting point for students to learn to think critically about healthcare claims and choices.
The “Trauma Pitch”: How stigma emerges for Iraq and Afghanistan veterans seeking disability compensation
Authors: Hooyer Katinka
Published: April 2022

Posttraumatic Stress Disorder continues to be a highly stigmatized disease for the veteran population and stigma continues to be identified as the main deterrent in treatment seeking. Little attention has been paid to how the process of obtaining service-connected disability status can amplify veterans’ perceptions of being stigmatized. The following ethnographic study identified how combat veterans experienced stigma in processing through Veterans Affairs care and the effects of linking a Posttraumatic Stress Disorder diagnosis with disability compensation to perceived stigmas. Stigma was identified in two inter-related areas: 1) the structural level in the Veterans Affairs disability claims process and 2) the individual level in interactions with Veterans Affairs service providers. Results based on veterans’ narratives suggest that the disability claims process, requiring multiple repetitions of personal trauma, coupled with perceptions of institutional stigmas of malingering, created bureaugenic effects: a worsening of symptoms caused by bureaucratic protocols intended to help veterans. This process influenced first time treatment users of the Veterans Affairs by deterring treatment-seeking behavior but was not found to affect veterans who had already initiated treatment. Despite the experience of stigma and commodification of their suffering through disability and diagnostic screening, veterans still sought disability compensation. Veterans viewed this compensation as acknowledgment of their loss and validation of their sacrifice.
Heterogeneity of resting-state EEG features in juvenile myoclonic epilepsy and controls
Authors: Shakeshaft Amy , Laiou Petroula , Abela Eugenio , Stavropoulos Ioannis , Richardson Mark P. , Pal Deb K.
Published: April 2022

Abnormal EEG features are a hallmark of epilepsy, and abnormal frequency and network features are apparent in EEGs from people with idiopathic generalised epilepsy in both ictal and interictal states. Here, we characterise differences in the resting-state EEG of individuals with juvenile myoclonic epilepsy (JME) and assess factors influencing the heterogeneity of these EEG features. We collected EEG data from 147 participants with JME through the Biology of Juvenile Myoclonic Epilepsy (BIOJUME) study. 95 control EEGs were acquired from two independent studies (Chowdhury et al. (2014) and EU-AIMS Longitudinal European Autism Project). We extracted frequency and functional network-based features from 10-20s epochs of resting-state EEG, including relative power spectral density (PSD), peak alpha frequency, network topology measures and Brain Network Ictogenicity (BNI): a computational measure of the propensity of networks to generate seizure dynamics. The influence of covariates such as age, sex, antiseizure medication, EEG time and epoch length were investigated for each EEG feature prior to testing for differences between JME and control EEGs using univariate, multivariable and receiver operating curve (ROC) analysis. Additionally, associations of clinical phenotypes (seizure type, seizure control) with EEG features were investigated in the JME cohort. P-values were corrected for multiple comparisons. Univariate analysis showed significant differences in PSD in delta (2-5Hz) (p=0.0007, hedges’ g=0.55) and low-alpha (6-9Hz) (p=2.9×10-8, g=0.80) frequency bands, peak alpha frequency (p=0.000007, g=0.66), functional network mean degree (p=0.0006, g=0.48) and BNI (p=0.00006, g=0.56) between JME and controls. Since age (p=0.009) and epoch length (p=1.7×10-8) differed between the two groups and were potential confounders, we controlled for these covariates in multivariable analysis where disparities in EEG features between JME and controls remained. ROC analysis showed low-alpha PSD was optimal at distinguishing JME from controls, with an area under the curve of 0.72. Lower average normalized clustering coefficient and shorter average normalized path length were associated with poorer seizure control in JME patients. To conclude, individuals with JME have increased power of neural oscillatory activity at low-alpha frequencies, along with increased BNI compared to controls, supporting evidence from studies in other epilepsies with considerable external validity. In addition, the impact of confounders on different frequency-based and network-based EEG features observed in this study highlights the need for careful consideration and control of these factors in future EEG research in IGE particularly for their use as biomarkers.
Patterns of impaired neurocognitive performance on Global Neuropsychological Assessment (GNA), and their brain structural correlates in recent-onset and chronic schizophrenia: A pilot study
Authors: Mohan Vineeth , Parekh Pravesh , Lukose Ammu , Moirangthem Sydney , Saini Jitender , Schretlen David J , John John P
Published: April 2022

Cognitive deficits are established as a fundamental feature of schizophrenia; however, their pattern and how they are affected by chronicity are still unclear. Although a generalized stable impairment affecting multiple cognitive domains is commonly seen from the onset, some longitudinal studies have shown evidence of neuroprogression, and selective deterioration in certain cognitive domains. We assessed cognitive performance in patients with recent-onset (n= 17, duration of illness ≤ 2 years) and chronic schizophrenia (n= 14, duration ≥ 15 years), and healthy adults (n= 16) using the Global Neuropsychological Assessment and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted MRI images. We also measured and analyzed differences between patient groups for negative and positive symptoms, psychotic exacerbations, and medication exposure, and studied their correlations with cognitive performances. We observed cognitive deficits affecting multiple domains in both recent-onset and chronic schizophrenia samples. Selectively greater impairment of perceptual comparison/processing speed was found in adults with chronic schizophrenia (p= 0.009, η2partial= 0.25). In the full sample (n= 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes, predominantly on the left side (TFCE, FWEp< 0.01). These results indicate that along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison/processing speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Gray matter volumetric deficits in the anterior-medial temporal lobes especially of left side might underlie the impaired perceptual comparison/processing speed seen in schizophrenia.
Comparative and Integrated Analysis of Plasma Extracellular Vesicles Isolations Methods in Healthy Volunteers and Patients Following Myocardial Infarction
Authors: Paget Daan , Checa Antonio , Zöhrer Benedikt , Heilig Raphael , Shanmuganathan Mayooran , Dhaliwal Raman , Johnson Errin , Jørgensen Maléne Møller , Bæk Rikke ,   Oxford Acute Myocardial Infarction Study (OxAMI), Wheelock Craig E. , Channon Keith M. , Fischer Roman , Anthony Daniel C. , Choudhury Robin P. , Akbar Naveed
Published: April 2022

Plasma extracellular vesicle (EV) number and composition are altered following myocardial infarction (MI), but to properly understand the significance of these changes it is essential to appreciate how the different isolation methods affect EV characteristics, proteome and sphingolipidome. Here, we compared plasma EV isolated from platelet-poor plasma from four healthy donors and six MI patients at presentation and 1-month post-MI using ultracentrifugation, polyethylene glycol precipitation, acoustic trapping, size-exclusion chromatography (SEC) or immunoaffinity capture. The isolated EV were evaluated by Nanoparticle Tracking Analysis, Western blot, transmission electron microscopy, an EV-protein array, untargeted proteomics (LC-MS/MS) and targeted sphingolipidomics (LC-MS/MS). The application of the five different plasma EV isolation methods in patients presenting with MI showed that the choice of plasma EV isolation method influenced the ability to distinguish elevations in plasma EV concentration following MI, enrichment of EV-cargo (EV-proteins and sphingolipidomics) and associations with the size of the infarct determined by cardiac magnetic resonance imaging 6 months-post-MI. Despite the selection bias imposed by each method, a core of EV associated proteins and lipids was detectable using all approaches. However, this study highlights how each isolation method comes with its own idiosyncrasies and makes the comparison of data acquired by different techniques in clinical studies problematic.
Early detection of patients with narcotic use disorder using a modified MEDD score based on the analysis of real-world prescription patterns
Authors: Kim Yi-Jun , Lee Kye Hwa , Kang Hye-Ryun , Cho Yoon Sook , Kang Dong Yoon , Kim Ju Han , Kim Yon Su
Published: April 2022

Background

Addiction to prescription narcotics is a global issue, and detection of individuals with a narcotic use disorder (NUD) at an early stage can help prevent narcotics misuse and abuse. We developed a novel index to detect early NUD based on a real-world prescription pattern analysis in a large hospital.

Methods

We analyzed narcotic prescriptions of 221 887 patients prescribed by 8737 doctors from July 2000 to June 2018. For the early detection of patients who could potentially progress to developing NUD after a long history of narcotic prescription, a weighted morphine equivalent daily dose (wt-MEDD) score was developed based on the number of prescription dates on which the actual MEDD was higher than the intended MEDD. Performance of the wt-MEDD scoring system in detecting patients diagnosed with NUD by doctors was compared with that of other NUD high risk indexes such as the MEDD scoring system, number of days on prescribed narcotics, the frequency/duration of prescription, narcotics prescription across multiple doctors, and the number of early refills of narcotics.

Results

A wt-MEDD score cut-off value of 10.5 could detect all outliers, as well as patients diagnosed with NUD with 100% sensitivity and 99.6% specificity. The wt-MEDD score showed the highest sensitivity and specificity in identifying NUD among all indexes. Further, combining the wt-MEDD score with other NUD high risk indexes improved the prediction performance.

Conclusion

We developed a novel index to distinguish patients with vulnerable use patterns of narcotics. The wt-MEDD score showed excellent performance in detecting early NUD.
COVID-19 in the Mexican Social Security Institute (IMSS) population. Prevalent symptoms
Authors: Juárez-Flores Arturo , Ascencio-Montiel Iván J. , Gutiérrez Juan Pablo , Bertozzi Stefano M. , Borja-Aburto Víctor H. , Olaiz Gustavo
Published: April 2022

Background

The disease caused by the new coronavirus SARS-CoV-2, COVID-19, which appeared in early 2020 in Mexico, was the second leading cause of mortality in the country that year and has generated an increasing demand for medical care. By January 2022, 4.13 million cases and 300 thousand direct deaths have been documented.

Objective

To describe the main symptoms of people with a positive test for SARS-CoV-2 treated at the Mexican Institute of Social Security (IMSS) by sex, age group, and IMSS delegation.

Methods

4.5 million epidemiological reports were registered in the IMSS epidemiological surveillance system between February 2020 and November 2021. They were analyzed, reporting for those with either a positive PCR or rapid test, the prevalence of symptoms by sex, groups of age, and IMSS delegation.

Results

Among the population treated at the IMSS, six symptoms are observed as the most prevalent in general, as well as by sex, age groups, and state of residence: cefalea, fever, cough, myalgia, odynophagia, and arthralgias.

Conclusions

A better understanding of the clinical picture with which confirmed cases of COVID-19 present contributes to reporting timely diagnoses, considering the particularities by sex, age, and place of residence.
High prevalence of burnout syndrome among medical and nonmedical residents during the COVID-19 pandemic
Authors: Pinho Rebeca da Nóbrega Lucena , Costa Thais Ferreira , Silva Nayane Miranda , Barros Areal Adriana Ferreira , Salles André de Matos , Oliveira Andrea Pedrosa Ribeiro Alves , Esselin Rassi Carlos Henrique Reis , Gomes Ciro Martins , Silva Dayde Lane Mendonça da , Oliveira Fernando Araújo Rodrigues de , Jochims Isadora , Vaz Filho Ivan Henrique Ranulfo , Oliveira Lucas Alves de Brito , Rosal Marta Alves , Lima Marta Pinheiro , Soares Mayra Veloso Ayrimoraes , Kurisky Patrícia Shu , Pertele Viviane Cristina Uliana , Gomides Ana Paula Monteiro , Mota Licia Maria Henrique da , Albuquerque Cleandro Pires de , Simaan Cezar Kozak , Amado Veronica Moreira
Published: April 2022

Background

Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis.

Methods

Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Student’s t test, Pearson’s correlation test and logistic regression were performed.

Results

A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26– 2.47]) and weekly work > 60 h (1.36 [1.03–1.79]) and were lower in the presence of high resilience (0.84 [0.81–0.88]), autonomy (0.87 [0.81–0.93]), and educational structure (0.77 [0.73–0.82]), adequate availability of PPE (0.72 [0.63–0.83]) and non-white race (0.63 [0.47–0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05).

Conclusions

We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.
Triangulating evidence in health sciences with Annotated Semantic Queries
Authors: Liu Yi , Gaunt Tom R
Published: April 2022

Integrating information from data sources representing different study designs has the potential to strengthen evidence in population health research. However, this concept of evidence “triangulation” presents a number of challenges for systematically identifying and integrating relevant information. We present ASQ (Annotated Semantic Queries), a natural language query interface to the integrated biomedical entities and epidemiological evidence in EpiGraphDB, which enables users to extract “claims” from a piece of unstructured text, and then investigate the evidence that could either support, contradict the claims, or offer additional information to the query. This approach has the potential to support the rapid review of pre-prints, grant applications, conference abstracts and articles submitted for peer review. ASQ implements strategies to harmonize biomedical entities in different taxonomies and evidence from different sources, to facilitate evidence triangulation and interpretation. ASQ is openly available athttps://asq.epigraphdb.org.
A Text Message Intervention to Support Latino Dementia Family Caregivers (CuidaTEXT): Feasibility study
Authors: Perales-Puchalt Jaime , Ramírez-Mantilla Mariana , Fracachán-Cabrera Mónica , Vidoni Eric D. , Ellerbeck Edward F. , Ramírez A. Susana , Watts Amber , Williams Kristine , Burns Jeffrey
Published: April 2022

Objectives

To test the feasibility, acceptability, and preliminary efficacy of CuidaTEXT: a tailored text message intervention to support Latino dementia family caregivers.

Methods

CuidaTEXT is a six-month, bilingual, and bidirectional intervention tailored to caregiver needs (e.g., education, problem-solving, resources). We enrolled 24 Latino caregivers in a one-arm trial, and assessed feasibility, acceptability, and preliminary efficacy within six months.

Results

Recruitment took 61 days and enrollment took 20. None of the participants unsubscribed from CuidaTEXT, and 83.3% completed the follow up survey. Most participants (85.7%) reported reading most text messages thoroughly. Participants reported high levels of satisfaction with the intervention (3.6 on a scale from 1 to 4). CuidaTEXT helpfulness was high (3.5-3.8 on a 1 to 4 scale). Compared to baseline, at six months caregiver behavioral symptom distress (0–60) decreased from 19.8 to 12.0, and depression (0-30) from 8.8 to 5.4 (p<0.05).

Conclusions

CuidaTEXT demonstrated high levels of feasibility, acceptability, and preliminary efficacy among Latino caregivers.

Clinical implications

CuidaTEXT’s feasibility and potential for widespread implementation holds promise in supporting Latino caregivers of people with dementia.
Convolutional networks for supervised mining of molecular patterns within cellular context
Authors: de Teresa Irene , Goetz Sara K. , Mattausch Alexander , Stojanovska Frosina , Zimmerli Christian E. , Toro-Nahuelpan Mauricio , Cheng Dorothy W.C. , Tollervey Fergus , Pape Constantin , Beck Martin , Kreshuk Anna , Mahamid Julia , Zaugg Judith
Published: April 2022

Cryo-electron tomograms capture a wealth of structural information on the molecular constituents of cells and tissues. We present DeePiCt (Deep Picker in Context), an open-source deep-learning framework for supervised structure segmentation and macromolecular complex localization in cellular cryo-electron tomography. To train and benchmark DeePiCt on experimental data, we comprehensively annotated 20 tomograms ofSchizosaccharomyces pombefor ribosomes, fatty acid synthases, membranes, nuclear pore complexes, organelles and cytosol. By comparing our method to state-of-the-art approaches on this dataset, we show its unique ability to identify low-abundance and low-density complexes. We use DeePiCt to study compositionally-distinct subpopulations of cellular ribosomes, with emphasis on their contextual association with mitochondria and the endoplasmic reticulum. Finally, by applying pre-trained networks to a HeLa cell dataset, we demonstrate that DeePiCt achieves high-quality predictions in unseen datasets from different biological species in a matter of minutes. The comprehensively annotated experimental data and pre-trained networks are provided for immediate exploitation by the community.
Origin of Protein Quake: Energy Waves Conducted by a Precise Mechanical Machine
Authors: Li Huiyu , Wu Shanshan , Ma Ao
Published: April 2022

A long-standing challenge in protein biophysics is to understand protein quake in myoglobin—the structural dynamics responsible for redistributing the excess heme energy after photolysis. Despite extensive efforts, the molecular mechanism of this process remains elusive. Using the energy flow theory, we uncovered a fundamental new phenomenon: the heme energy is redistributed by energy waves with a ubiquitous fundamental frequency and two overtones. Energy waves emanate from the heme into the myoglobin backbone via a conduit of five consecutive dihedrals of the proximal histidine, then travel quickly along the backbone to reach sidechains across the protein. This mechanism is far more effective than the diffusion-based mechanism from previous studies because waves are systematic while diffusion is random. To propagate energy waves, coordinates must cooperate, resulting in collective modes that are singular vectors of the generalized work functional. These modes show task partitioning: a handful of high-energy modes generate large-scale breathing motion, which loosens up the protein matrix to enable hundreds of low-energy vibrational modes for energy transduction.
Interpreting the pervasive observation of U-shaped Site Frequency Spectra
Authors: Freund Fabian , Kerdoncuff Elise , Matuszewski Sebastian , Lapierre Marguerite , Hildebrandt Marcel , Jensen Jeffrey D. , Ferretti Luca , Lambert Amaury , Sackton Timothy B. , Achaz Guillaume
Published: April 2022

The standard neutral model of molecular evolution has traditionally been used as the null model for population genomics. We gathered a collection of 45 genome-wide site frequency spectra from a diverse set of species, most of which display an excess of low and high frequency variants compared to the expectation of the standard neutral model, resulting in U-shaped spectra. We show that multiple merger coalescent models often provide a better fit to these observations than the standard Kingman coalescent. Hence, in many circumstances these under-utilized models may serve as the more appropriate reference for genomic analyses. We further discuss the underlying evolutionary processes that may result in the widespread U-shape of frequency spectra.
Improving the fidelity of uridine analog incorporation during in vitro transcription
Authors: Chen Tien-Hao , Potapov Vladimir , Dai Nan , Ong Jennifer L. , Roy Bijoyita
Published: April 2022

In vitro transcribed synthetic messenger RNAs (mRNAs) represent a novel therapeutic modality and are currently being evaluated for a wide range of clinical indications. To overcome the inherent immunogenicity of the synthetic mRNAs, as well as to increase the therapeutic efficacy of the molecules, RNA sequence optimization is routinely performed and modified uridine analogs—such as pseudouridine (Ψ) and N1-methyl-pseudouridine (m1Ψ), are incorporated in the synthetic mRNA. To decipher the fidelity with which these modifications are incorporated during the in vitro transcription (IVT) process, here, we compared, the incorporation fidelity of uridine, Ψ, or m1Ψ in multiple RNA sequences with different single-subunit DNA-dependent RNA polymerases (ssRNAPs). By comparing the incorporation of each modified base to that of the unmodified equivalent, we demonstrate that m1Ψ is incorporated with higher fidelity than Ψ. Furthermore, the various ssRNAPs exhibit different error rates; however, the spectrum of mutations observed between the RNAPs is similar. We also show that the array of nucleotide misincorporation is not dependent on the template DNA sequence context and that the distribution of these misincorporated nucleotides is not localized to any specific region along the length of the RNA. Based on our findings, we introduce a novel protocol to improve uridine analog incorporation—without affecting total RNA yield—during IVT. Our proof-of-concept experiments and protocol for higher-fidelity incorporation of uridine analogs during IVT provide guidelines when choosing ssRNAPs for the generation of modified uridine—containing mRNAs in vitro.
Reelin deficiency exacerbates cocaine-induced hyperlocomotion by enhancing neuronal activity in the dorsomedial striatum
Authors: de Guglielmo Giordano , Iemolo Attilio , Nur Aisha , Turner Andrew , Montilla-Perez Patricia , Telese Francesca
Published: April 2022

The Reln gene encodes for the extracellular glycoprotein Reelin, which regulates several brain functions from development to adulthood, including neuronal migration, dendritic growth and branching, and synapse formation and plasticity. Human studies have implicated Reelin signaling in several neurodevelopmental and psychiatric disorders. Mouse studies using the heterozygous Reeler (HR) mice have shown that reduced levels of Reln expression are associated with deficits in learning and memory and increased disinhibition. Although these traits are relevant to substance use disorders, the role of Reelin in cellular and behavioral responses to addictive drugs remains largely unknown. Here, we compared HR mice to wild-type (WT) littermate controls to investigate the contribution of Reelin signaling to the hyper-locomotor and rewarding effects of cocaine. After a single cocaine injection, HR mice showed enhanced cocaine-induced locomotor activity compared to WT controls. After repeated injections of cocaine, Reelin deficiency also led to increased cocaine-induced locomotor sensitization, which persisted after withdrawal. In contrast, Reelin deficiency did not affect the rewarding effects of cocaine measured in the conditioned place preference assay. The elevated cocaine-induced hyper-locomotion in HR mice resulted in increased Fos expression in the dorsal medial striatum (DMS) compared to WT. Lastly, we found that Reln was highly co-expressed with the Drd1 gene, which encodes for the dopamine receptor D1, in the DMS.

These findings demonstrated that Reelin signaling contributes to the locomotory effects of cocaine and improved our understanding of the neurobiological mechanisms underlying the cellular and behavioral effects of cocaine.
Benchmarking community-wide estimates of growth potential from metagenomes using codon usage statistics
Authors: Weissman JL , Peras Marie , Barnum Tyler P. , Fuhrman Jed A.
Published: April 2022

Trait inference from mixed-species assemblages is a central problem in microbial ecology. Frequently, sequencing information from an environment is available, but phenotypic measurements from individual community members are not. With the increasing availability of molecular data for microbial communities, bioinformatic approaches that map metagenome to (meta)phenotype are needed. Recently, we developed a tool, gRodon, that enables the prediction of the maximum growth rate of an organism from genomic data on the basis of codon usage patterns. Our work and that of other groups suggests that such predictors can be applied to mixed-species communities in order to derive estimates of the average community-wide maximum growth rate. Here, we present an improved maximum growth rate predictor designed for metagenomes that corrects a persistent GC bias in the original gRodon model for metagenomic prediction. We benchmark this predictor with simulated metagenomic datasets to show that it has superior performance on mixed-species communities relative to earlier models. We go on to provide guidance on data pre-processing, and show that calling genes from assembled contigs rather than directly from reads dramatically improves performance. Finally, we apply our predictor to large-scale metagenomic datasets from marine and human microbiomes to illustrate how community-wide growth prediction can be a powerful approach for hypothesis-generation. Altogether, we provide an updated tool with clear guidelines for users about the uses and pitfalls of metagenomic prediction of the average community-wide maximal growth rate.
Tuned inhibitory firing rate and connection weights as emergent network properties
Authors: Lagzi Fereshteh , Fairhall Adrienne
Published: April 2022

Excitatory cortical neurons show clear tuning to stimulus features, but the tuning properties of inhibitory neurons are ambiguous and have been the subject of a long debate. While inhibitory neurons have been considered to be largely untuned [1–4], recent studies show that some parvalbumin expressing (PV) neurons do show feature selectivity and participate in co-tuned subnetworks with pyramidal cells in which PV cells show high response similarity to the excitatory (E) neurons [5, 6]. Given shared input from layer 4 that drives feature tuning in excitatory subnetworks, we demonstrate that homeostatic regulation of postsynaptic firing rate governing the synaptic dynamics of the connections from PV to E cells, in combination with heterogeneity in the excitatory postsynaptic potentials (EPSP) that impinge on PV cells, results in the self-organization of PV subnetworks. We reconcile different experimental findings by showing that feature tuning of PV cells is an emerging network property that may be driven by synaptic heterogeneity, and can be inferred using population-level measures, while pairwise individual-level measures may fail to reveal inhibitory tuning. We show that such co-tuning can enhance network stability at the cost of response salience.