Effective utilization of academic literature is crucial for Machine Reading Comprehension to generate actionable scientific knowledge for wide real-world applications. Recently, Large Language Models (LLMs) have emerged as a powerful tool for distilling knowledge from scientific articles, but they struggle with the issues of reliability and verifiability. Here, we propose LORE, a novel unsupervised two-stage reading methodology with LLM that models literature as a knowledge graph of verifiable factual statements and, in turn, as semantic embeddings in Euclidean space. Applied to PubMed abstracts for large-scale understanding of disease-gene relationships, LORE captures essential information of gene pathogenicity. Furthermore, we demonstrate that modeling a latent pathogenic flow in the semantic embedding with supervision from the ClinVar database leads to a 90% mean average precision in identifying relevant genes across 2,097 diseases. Finally, we have created a disease-gene relation knowledge graph with predicted pathogenicity scores, 200 times larger than the ClinVar database.
{"title":"LORE: A Literature Semantics Framework for Evidenced Disease-Gene Pathogenicity Prediction at Scale","authors":"P.-H. Li, Y.-Y. Sun, H.-F. Juan, C.-Y. Chen, H.-K. Tsai, J.-H. Huang","doi":"10.1101/2024.08.10.24311801","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311801","url":null,"abstract":"Effective utilization of academic literature is crucial for Machine Reading Comprehension to generate actionable scientific knowledge for wide real-world applications. Recently, Large Language Models (LLMs) have emerged as a powerful tool for distilling knowledge from scientific articles, but they struggle with the issues of reliability and verifiability. Here, we propose LORE, a novel unsupervised two-stage reading methodology with LLM that models literature as a knowledge graph of verifiable factual statements and, in turn, as semantic embeddings in Euclidean space. Applied to PubMed abstracts for large-scale understanding of disease-gene relationships, LORE captures essential information of gene pathogenicity. Furthermore, we demonstrate that modeling a latent pathogenic flow in the semantic embedding with supervision from the ClinVar database leads to a 90% mean average precision in identifying relevant genes across 2,097 diseases. Finally, we have created a disease-gene relation knowledge graph with predicted pathogenicity scores, 200 times larger than the ClinVar database.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"4 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.10.24311776
S. Nag, S. Banerjee, A. Bandopadhyay, I. Banerjee, S. Jana, A. Mondal, S. Chakraborty
Early diagnosis of active viral co-infections of similar symptomatic pattern is critical for preventing life-threatening respiratory complications. While facilities for the same are currently available, those are either over-expensive or not amenable for deployment in resource-limited settings. We report a first of its kind isothermal colorimetric nucleic acid-based test integrated in a user-friendly, portable device, that can differentially diagnose respiratory viral infections having similar symptomatic pattern, and illustrate its performance by detecting co-infections of SARS-CoV-2 with seasonal influenza A virus from unprocessed swab sample in an extraction-free analysis mode within 45 minutes without intermediate manual steps. The test obviates the need of any complex disposable cartridge in preference to common laboratory utilities. Further, it harnesses machine learning empowered and smartphone interfaced colorimetric analysis without needing any specialized optical detector. The efficacy of the test is validated via community-adapted randomized field trials at underserved rural settings by frontline health workers, reporting sensitivity >96% and specificity > 98% in 1500 cohorts. The method in the form of three test genes with one internal control assay evidences to facilitate viral surveillance and enables diagnosing complex respiratory infections early enough in a plethora of settings ranging from general hospitals to the community centres, overcoming barriers to access of high-end facilities. Such adaptation of scientifically supreme multiplex nucleic acid based diagnostics in the framework of a simple and user friendly rapid test appears to be the future of infectious disease management in a democratized framework, eradicating the disparities in affordability and accessibility in resource-limited settings.
{"title":"CO-INFECTS: A Highly Affordable, Portable, Nucleic-Acid-Based Rapid Detector of Active Respiratory Co-Infections via \"Swab-to-Result\" Integration","authors":"S. Nag, S. Banerjee, A. Bandopadhyay, I. Banerjee, S. Jana, A. Mondal, S. Chakraborty","doi":"10.1101/2024.08.10.24311776","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311776","url":null,"abstract":"Early diagnosis of active viral co-infections of similar symptomatic pattern is critical for preventing life-threatening respiratory complications. While facilities for the same are currently available, those are either over-expensive or not amenable for deployment in resource-limited settings. We report a first of its kind isothermal colorimetric nucleic acid-based test integrated in a user-friendly, portable device, that can differentially diagnose respiratory viral infections having similar symptomatic pattern, and illustrate its performance by detecting co-infections of SARS-CoV-2 with seasonal influenza A virus from unprocessed swab sample in an extraction-free analysis mode within 45 minutes without intermediate manual steps. The test obviates the need of any complex disposable cartridge in preference to common laboratory utilities. Further, it harnesses machine learning empowered and smartphone interfaced colorimetric analysis without needing any specialized optical detector. The efficacy of the test is validated via community-adapted randomized field trials at underserved rural settings by frontline health workers, reporting sensitivity >96% and specificity > 98% in 1500 cohorts. The method in the form of three test genes with one internal control assay evidences to facilitate viral surveillance and enables diagnosing complex respiratory infections early enough in a plethora of settings ranging from general hospitals to the community centres, overcoming barriers to access of high-end facilities. Such adaptation of scientifically supreme multiplex nucleic acid based diagnostics in the framework of a simple and user friendly rapid test appears to be the future of infectious disease management in a democratized framework, eradicating the disparities in affordability and accessibility in resource-limited settings.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.10.24311802
H. Karimi-Rouzbahani, A. McGonigal
Epilepsy affects over 50 million people worldwide, with approximately 30% experiencing drug-resistant forms that may require surgical intervention. Accurate localisation of the epileptogenic zone (EZ) is crucial for effective treatment, but how best to use intracranial EEG data to delineate the EZ remains unclear. Previous studies have used the directionality of neural activities across the brain to investigate seizure dynamics and localise the EZ. However, the different connectivity measures used across studies have often provided inconsistent insights about the direction and the localisation power of signal flow as a biomarker for EZ localisation. In a data-driven approach, this study employs a large set of 13 distinct directed connectivity measures to evaluate neural activity flow in and out the seizure onset zone (SOZ) during interictal and ictal periods. These measures test the hypotheses of sink SOZ (SOZ dominantly receiving neural activities during interictal periods) and source SOZ (SOZ dominantly transmitting activities during ictal periods). While the results were different across connectivity measures, several measures consistently supported higher connectivity directed towards the SOZ in interictal periods and higher connectivity directed away during ictal period. Comparing six distinct metrics of node behaviour in the network, we found that SOZ separates itself from the rest of the network allowing for the metric of eccentricity to localise the SOZ more accurately than any other metrics including in-strength and out-strength. This introduced a novel biomarker for localising the SOZ, leveraging the discriminative power of directed connectivity measures in an explainable machine learning pipeline. By using a comprehensive, objective and data-driven approach, this study addresses previously unresolved questions on the direction of neural activities in seizure organisation, and sheds light on dynamics of interictal and ictal activity in focal epilepsy.
{"title":"Directionality of neural activity in and out of the seizure onset zone in focal epilepsy","authors":"H. Karimi-Rouzbahani, A. McGonigal","doi":"10.1101/2024.08.10.24311802","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311802","url":null,"abstract":"Epilepsy affects over 50 million people worldwide, with approximately 30% experiencing drug-resistant forms that may require surgical intervention. Accurate localisation of the epileptogenic zone (EZ) is crucial for effective treatment, but how best to use intracranial EEG data to delineate the EZ remains unclear. Previous studies have used the directionality of neural activities across the brain to investigate seizure dynamics and localise the EZ. However, the different connectivity measures used across studies have often provided inconsistent insights about the direction and the localisation power of signal flow as a biomarker for EZ localisation. In a data-driven approach, this study employs a large set of 13 distinct directed connectivity measures to evaluate neural activity flow in and out the seizure onset zone (SOZ) during interictal and ictal periods. These measures test the hypotheses of sink SOZ (SOZ dominantly receiving neural activities during interictal periods) and source SOZ (SOZ dominantly transmitting activities during ictal periods). While the results were different across connectivity measures, several measures consistently supported higher connectivity directed towards the SOZ in interictal periods and higher connectivity directed away during ictal period. Comparing six distinct metrics of node behaviour in the network, we found that SOZ separates itself from the rest of the network allowing for the metric of eccentricity to localise the SOZ more accurately than any other metrics including in-strength and out-strength. This introduced a novel biomarker for localising the SOZ, leveraging the discriminative power of directed connectivity measures in an explainable machine learning pipeline. By using a comprehensive, objective and data-driven approach, this study addresses previously unresolved questions on the direction of neural activities in seizure organisation, and sheds light on dynamics of interictal and ictal activity in focal epilepsy.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.10.24311802
H. Karimi-Rouzbahani, A. McGonigal
Epilepsy affects over 50 million people worldwide, with approximately 30% experiencing drug-resistant forms that may require surgical intervention. Accurate localisation of the epileptogenic zone (EZ) is crucial for effective treatment, but how best to use intracranial EEG data to delineate the EZ remains unclear. Previous studies have used the directionality of neural activities across the brain to investigate seizure dynamics and localise the EZ. However, the different connectivity measures used across studies have often provided inconsistent insights about the direction and the localisation power of signal flow as a biomarker for EZ localisation. In a data-driven approach, this study employs a large set of 13 distinct directed connectivity measures to evaluate neural activity flow in and out the seizure onset zone (SOZ) during interictal and ictal periods. These measures test the hypotheses of sink SOZ (SOZ dominantly receiving neural activities during interictal periods) and source SOZ (SOZ dominantly transmitting activities during ictal periods). While the results were different across connectivity measures, several measures consistently supported higher connectivity directed towards the SOZ in interictal periods and higher connectivity directed away during ictal period. Comparing six distinct metrics of node behaviour in the network, we found that SOZ separates itself from the rest of the network allowing for the metric of eccentricity to localise the SOZ more accurately than any other metrics including in-strength and out-strength. This introduced a novel biomarker for localising the SOZ, leveraging the discriminative power of directed connectivity measures in an explainable machine learning pipeline. By using a comprehensive, objective and data-driven approach, this study addresses previously unresolved questions on the direction of neural activities in seizure organisation, and sheds light on dynamics of interictal and ictal activity in focal epilepsy.
{"title":"Directionality of neural activity in and out of the seizure onset zone in focal epilepsy","authors":"H. Karimi-Rouzbahani, A. McGonigal","doi":"10.1101/2024.08.10.24311802","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311802","url":null,"abstract":"Epilepsy affects over 50 million people worldwide, with approximately 30% experiencing drug-resistant forms that may require surgical intervention. Accurate localisation of the epileptogenic zone (EZ) is crucial for effective treatment, but how best to use intracranial EEG data to delineate the EZ remains unclear. Previous studies have used the directionality of neural activities across the brain to investigate seizure dynamics and localise the EZ. However, the different connectivity measures used across studies have often provided inconsistent insights about the direction and the localisation power of signal flow as a biomarker for EZ localisation. In a data-driven approach, this study employs a large set of 13 distinct directed connectivity measures to evaluate neural activity flow in and out the seizure onset zone (SOZ) during interictal and ictal periods. These measures test the hypotheses of sink SOZ (SOZ dominantly receiving neural activities during interictal periods) and source SOZ (SOZ dominantly transmitting activities during ictal periods). While the results were different across connectivity measures, several measures consistently supported higher connectivity directed towards the SOZ in interictal periods and higher connectivity directed away during ictal period. Comparing six distinct metrics of node behaviour in the network, we found that SOZ separates itself from the rest of the network allowing for the metric of eccentricity to localise the SOZ more accurately than any other metrics including in-strength and out-strength. This introduced a novel biomarker for localising the SOZ, leveraging the discriminative power of directed connectivity measures in an explainable machine learning pipeline. By using a comprehensive, objective and data-driven approach, this study addresses previously unresolved questions on the direction of neural activities in seizure organisation, and sheds light on dynamics of interictal and ictal activity in focal epilepsy.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"17 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.10.24311393
B. Cracknell Daniels, N. M. Ferguson, I. Dorigatti
Dengue is the most common arboviral infection, causing substantial morbidity and mortality globally. The licensing of Qdenga, a second-generation vaccine developed by Takeda Pharmaceuticals, is therefore timely, but the potential public health impact of vaccination across transmission settings needs to be evaluated. To address this, we characterised Qdenga's efficacy profile using mathematical models calibrated to published clinical trial data and estimated the public health impact of routine vaccine use. We find that efficacy depends on the infecting serotype, serological status, and age. We estimate that vaccination of children aged over six years in moderate to high dengue transmission settings (seroprevalence at 9 years of age > 60%) could reduce the burden of hospitalised dengue by 10-22% on average over ten years. We find some evidence of a risk of vaccine-induced disease enhancement in seronegative vaccine recipients for dengue serotypes 3 and 4, especially for children under six years of age. Because of this, the benefits of vaccination in lower transmission settings are more uncertain, and more data on the long-term efficacy of Qdenga against serotypes 3 and 4 are needed.
{"title":"Efficacy, public health impact and optimal use of the Takeda dengue vaccine","authors":"B. Cracknell Daniels, N. M. Ferguson, I. Dorigatti","doi":"10.1101/2024.08.10.24311393","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311393","url":null,"abstract":"Dengue is the most common arboviral infection, causing substantial morbidity and mortality globally. The licensing of Qdenga, a second-generation vaccine developed by Takeda Pharmaceuticals, is therefore timely, but the potential public health impact of vaccination across transmission settings needs to be evaluated. To address this, we characterised Qdenga's efficacy profile using mathematical models calibrated to published clinical trial data and estimated the public health impact of routine vaccine use. We find that efficacy depends on the infecting serotype, serological status, and age. We estimate that vaccination of children aged over six years in moderate to high dengue transmission settings (seroprevalence at 9 years of age > 60%) could reduce the burden of hospitalised dengue by 10-22% on average over ten years. We find some evidence of a risk of vaccine-induced disease enhancement in seronegative vaccine recipients for dengue serotypes 3 and 4, especially for children under six years of age. Because of this, the benefits of vaccination in lower transmission settings are more uncertain, and more data on the long-term efficacy of Qdenga against serotypes 3 and 4 are needed.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.11.24311803
L. A. Marcano, R. S. Lugo
The role of oxidative stress and the use of biochemical biomarkers in the severity of COVID-19 was evaluated through a literature review (2020 to 2021) using scientific search engines such as PubMed, Science Direct, and Google Scholar. The search was limited to articles published in Spanish or English that reported on COVID-19 and its relationship with oxidative stress, following PRISMA-2020 guidelines. The search terms included oxidative stress, COVID-19, SARS-CoV-2, oxidative biomarkers, and oxidative damage. 93.5% of the selected studies were from the year 2021. These studies evaluated both oxidative stress biomarkers and oxidative damage biomarkers in COVID-19 patients. The reviewed studies reinforce the strong association of SARS-CoV-2 with oxidative stress and demonstrate how SARS-CoV-2-induced ROS production and disruption of the antioxidant defense system trigger a pro-inflammatory environment and cause severe tissue damage. In 64.7% of the studies, a combination of oxidative stress biomarkers (antioxidant and oxidative damage biomarkers) was used to assess COVID-19 severity. The most commonly used antioxidant biomarkers were thiols and total antioxidant capacity, followed by glutathione. The most commonly used oxidative damage biomarkers were malondialdehyde and peroxides, followed by advanced oxidation protein products. COVID-19 leads to a decrease in the antioxidant defense system, reflected by a decrease in antioxidant biomarkers and an increase in oxidative damage biomarkers.
{"title":"Use of Biochemical Biomarkers to Evaluate the Role of Oxidative Stress in the Progression of COVID-19 Severity","authors":"L. A. Marcano, R. S. Lugo","doi":"10.1101/2024.08.11.24311803","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311803","url":null,"abstract":"The role of oxidative stress and the use of biochemical biomarkers in the severity of COVID-19 was evaluated through a literature review (2020 to 2021) using scientific search engines such as PubMed, Science Direct, and Google Scholar. The search was limited to articles published in Spanish or English that reported on COVID-19 and its relationship with oxidative stress, following PRISMA-2020 guidelines. The search terms included oxidative stress, COVID-19, SARS-CoV-2, oxidative biomarkers, and oxidative damage. 93.5% of the selected studies were from the year 2021. These studies evaluated both oxidative stress biomarkers and oxidative damage biomarkers in COVID-19 patients. The reviewed studies reinforce the strong association of SARS-CoV-2 with oxidative stress and demonstrate how SARS-CoV-2-induced ROS production and disruption of the antioxidant defense system trigger a pro-inflammatory environment and cause severe tissue damage. In 64.7% of the studies, a combination of oxidative stress biomarkers (antioxidant and oxidative damage biomarkers) was used to assess COVID-19 severity. The most commonly used antioxidant biomarkers were thiols and total antioxidant capacity, followed by glutathione. The most commonly used oxidative damage biomarkers were malondialdehyde and peroxides, followed by advanced oxidation protein products. COVID-19 leads to a decrease in the antioxidant defense system, reflected by a decrease in antioxidant biomarkers and an increase in oxidative damage biomarkers.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.10.24311725
Kehinde Awodele, Sunday Charles Adeyemo, Eniola Dorcas, Olabode, A. Fasanu, Akintunde Rasaq Akindele, O. Adegboyega, Abidemi Olagunju, Olusegun Oyerinde, Lanre Olaitan
Male infertility accounts for nearly half of the infertility cases globally. Seminal fluid analysis (SFA) is a critical diagnostic tool in the evaluation of male infertility. This study aimed to assess the implications of seminal fluid analysis on male infertility among patients attending fertility clinics in Osogbo, Nigeria. The study employed mixed-method approach of both qualitative (Key informant interview) among 10 participants and quantitative method (cross-sectional survey) using pre-tested structured questionnaire among 305 respondents. The respondents in the cross-sectional survey were also made to undergo seminal fluid analysis. The data from the qualitative study was analysed using Atlas ti while data from the quantitative study were analysed using IBM Statistical Product for Service Solution (SPSS) version 27. 0. Descriptive statistics was carried out for all variables. The univariate, bivariate and multivariate analysis were done using p<0.05 as level of significance. The seminal fluid analysis of the respondents revealed that 241 (79.0%) had Normal sperm count (>32 million per ejaculation) while 64 (21.0%) had abnormal sperm count. Only 101 (33.1%) had normal progressive motility (>32 percent) while 204 (66.9%) had abnormal (Athenospermia) progressive motility. 195 (63.9%) were found to have abnormal morphology (Teratospermia i.e., <4%). The qualitative analysis further analysed the implications of SFA parameters on infertile males and these were substantial, extending beyond physical health to encompass psychological, emotional, and social well-being. The study concluded that lifestyle modifications and early diagnosis as well as prompt treatment of medical conditions can curb high prevalence abnormality of SFA, hence reduce male infertility in our environment. The study recommends that advocacy program, early screening and public health education will further reduce the burden of infertility among the female folks.
{"title":"MAJOR AETIOLOGIES OF MALE INFERTILITY AMONG COUPLES ATTENDING FERTILITY CLINICS IN OSUN STATE, NIGERIA: FINDINGS FROM A MIXED METHOD STUDY","authors":"Kehinde Awodele, Sunday Charles Adeyemo, Eniola Dorcas, Olabode, A. Fasanu, Akintunde Rasaq Akindele, O. Adegboyega, Abidemi Olagunju, Olusegun Oyerinde, Lanre Olaitan","doi":"10.1101/2024.08.10.24311725","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311725","url":null,"abstract":"Male infertility accounts for nearly half of the infertility cases globally. Seminal fluid analysis (SFA) is a critical diagnostic tool in the evaluation of male infertility. This study aimed to assess the implications of seminal fluid analysis on male infertility among patients attending fertility clinics in Osogbo, Nigeria. The study employed mixed-method approach of both qualitative (Key informant interview) among 10 participants and quantitative method (cross-sectional survey) using pre-tested structured questionnaire among 305 respondents. The respondents in the cross-sectional survey were also made to undergo seminal fluid analysis. The data from the qualitative study was analysed using Atlas ti while data from the quantitative study were analysed using IBM Statistical Product for Service Solution (SPSS) version 27. 0. Descriptive statistics was carried out for all variables. The univariate, bivariate and multivariate analysis were done using p<0.05 as level of significance. The seminal fluid analysis of the respondents revealed that 241 (79.0%) had Normal sperm count (>32 million per ejaculation) while 64 (21.0%) had abnormal sperm count. Only 101 (33.1%) had normal progressive motility (>32 percent) while 204 (66.9%) had abnormal (Athenospermia) progressive motility. 195 (63.9%) were found to have abnormal morphology (Teratospermia i.e., <4%). The qualitative analysis further analysed the implications of SFA parameters on infertile males and these were substantial, extending beyond physical health to encompass psychological, emotional, and social well-being. The study concluded that lifestyle modifications and early diagnosis as well as prompt treatment of medical conditions can curb high prevalence abnormality of SFA, hence reduce male infertility in our environment. The study recommends that advocacy program, early screening and public health education will further reduce the burden of infertility among the female folks.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"1 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.11.24311806
O. Rizk, S. Bick, B. White, K. Chidziwisano, R. Dreibelbis
Whilst improving hygiene and sanitation behaviours is key to cost-effective and sustainable WASH interventions, measuring behaviour change remains a challenge. This study assessed the validity and reliability of pictorial 24-hour recall (P24hR), a novel method using unprompted recall of past activities through pictures, compared to structured observation for measuring handwashing with soap (HWWS) and safe child faeces disposal in rural Malawi. Data were collected from 88 individuals across 74 households in Chiradzulu district using both methods over a two-day period, with the recall period of the P24hR corresponding to the period of structured observation completed the previous day. Results showed poor agreement between P24hR and observations in detection of hygiene opportunities and behaviours. P24hR under-reported handwashing opportunities when frequency was high and over-reported them when frequency was low. The 95% limits of agreement for handwashing opportunities estimated through Bland-Altman analysis (-7.62 to 4.89) were unacceptably wide given median 5 opportunities observed per participant. P24hR also over-reported HWWS and safe child faeces disposal, and kappa statistics indicated agreement no better than by chance. Structured observation remains the preferred method for measuring hygiene behaviours despite its known limitations, including potential reactivity bias.
{"title":"Assessing the reliability and validity of pictorial-assisted 24-hour recall for measuring hand hygiene and child faeces disposal: a cross-sectional study in Malawi","authors":"O. Rizk, S. Bick, B. White, K. Chidziwisano, R. Dreibelbis","doi":"10.1101/2024.08.11.24311806","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311806","url":null,"abstract":"Whilst improving hygiene and sanitation behaviours is key to cost-effective and sustainable WASH interventions, measuring behaviour change remains a challenge. This study assessed the validity and reliability of pictorial 24-hour recall (P24hR), a novel method using unprompted recall of past activities through pictures, compared to structured observation for measuring handwashing with soap (HWWS) and safe child faeces disposal in rural Malawi. Data were collected from 88 individuals across 74 households in Chiradzulu district using both methods over a two-day period, with the recall period of the P24hR corresponding to the period of structured observation completed the previous day. Results showed poor agreement between P24hR and observations in detection of hygiene opportunities and behaviours. P24hR under-reported handwashing opportunities when frequency was high and over-reported them when frequency was low. The 95% limits of agreement for handwashing opportunities estimated through Bland-Altman analysis (-7.62 to 4.89) were unacceptably wide given median 5 opportunities observed per participant. P24hR also over-reported HWWS and safe child faeces disposal, and kappa statistics indicated agreement no better than by chance. Structured observation remains the preferred method for measuring hygiene behaviours despite its known limitations, including potential reactivity bias.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.11.24311358
D. Alvarez-Sierra, M. Martinez-Gallo, A. Sanchez-Montalva, M. A. Fernandez-Sanmartin, R. Colobran, J. Espinosa-Pereiro, E. Poyatos-Canton, A. Sanchez-Pla, C. Zurera-Egea, C. Violan, R. Parra, H. Halzayat, A. Vivancos, F. Morandeira-Rego, B. Urban-Vargas, E. Martinez-Caceres, M. Hernandez-Gonzalez, J. Bas-Minguet, A. Teniente-Serra, P. Katsikis, R. Pujol Borrell
One possible determinant of COVID-19 severity is immune imprinting (IP) by Common Cold Coronavirus (CCCV). As IP occurs only in recall immune responses, we investigated the immune response to SARS-CoV-2 in a cohort of unvaccinated individual to determine whether their immune response aligned with the primary or recall immune response patterns. Analysis of the Ig isotype response trajectories to the Mpro, NP, and S structural proteins and the S RBD in this group of 191 patients and 44 controls revealed a pattern of recall response in 94.2 % of cases. The levels of antibodies correlated positively with the severity of the condition rather than a milder course. High-resolution flow cytometry of fresh PBMNCs showed trajectories of plasmablasts, B cell subsets, and cTfh, suggesting a recall response. The transcriptomic profile demonstrated that this group was directly comparable to other contemporary cohorts. Overall, these findings support the idea that the response to SARS-CoV-2 is, in most cases, a recall response, likely due to B and T memory cells to CCCV, and therefore susceptible to immune imprinting and antibody-dependent enhancement.
COVID-19严重程度的一个可能决定因素是普通感冒冠状病毒（CCCV）的免疫印记（IP）。由于 IP 只发生在召回免疫反应中，我们调查了一组未接种疫苗的个体对 SARS-CoV-2 的免疫反应，以确定他们的免疫反应是否与原发性或召回免疫反应模式一致。通过分析这组 191 名患者和 44 名对照者对 Mpro、NP 和 S 结构蛋白以及 S RBD 的 Ig 同型反应轨迹，发现 94.2% 的病例具有回忆反应模式。抗体水平与病情严重程度呈正相关，而不是病情较轻。新鲜 PBMNCs 的高分辨率流式细胞术显示了浆细胞、B 细胞亚群和 cTfh 的轨迹，表明存在回忆反应。转录组学特征显示，该组患者与其他当代组群患者具有直接可比性。总之，这些研究结果支持这样一种观点，即对 SARS-CoV-2 的反应在大多数情况下是一种回忆性反应，可能是由于 B 和 T 记忆细胞对 CCCV 的记忆，因此容易受到免疫印记和抗体依赖性增强的影响。
{"title":"The adaptive immune responses to SARS-CoV-2 as a recall response susceptible to immune imprinting","authors":"D. Alvarez-Sierra, M. Martinez-Gallo, A. Sanchez-Montalva, M. A. Fernandez-Sanmartin, R. Colobran, J. Espinosa-Pereiro, E. Poyatos-Canton, A. Sanchez-Pla, C. Zurera-Egea, C. Violan, R. Parra, H. Halzayat, A. Vivancos, F. Morandeira-Rego, B. Urban-Vargas, E. Martinez-Caceres, M. Hernandez-Gonzalez, J. Bas-Minguet, A. Teniente-Serra, P. Katsikis, R. Pujol Borrell","doi":"10.1101/2024.08.11.24311358","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311358","url":null,"abstract":"One possible determinant of COVID-19 severity is immune imprinting (IP) by Common Cold Coronavirus (CCCV). As IP occurs only in recall immune responses, we investigated the immune response to SARS-CoV-2 in a cohort of unvaccinated individual to determine whether their immune response aligned with the primary or recall immune response patterns. Analysis of the Ig isotype response trajectories to the Mpro, NP, and S structural proteins and the S RBD in this group of 191 patients and 44 controls revealed a pattern of recall response in 94.2 % of cases. The levels of antibodies correlated positively with the severity of the condition rather than a milder course. High-resolution flow cytometry of fresh PBMNCs showed trajectories of plasmablasts, B cell subsets, and cTfh, suggesting a recall response. The transcriptomic profile demonstrated that this group was directly comparable to other contemporary cohorts. Overall, these findings support the idea that the response to SARS-CoV-2 is, in most cases, a recall response, likely due to B and T memory cells to CCCV, and therefore susceptible to immune imprinting and antibody-dependent enhancement.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.1101/2024.08.11.24311809
Adam B. Smith, Darren C. Greenwood, Paul Williams, Joseph Kwon, Stavros Petrou, Mike Horton, Thomas Osborne, Ruairidh Milne, Locomotion Consortium, Manoj Sivan
Background: Long Covid (LC) is a clinical syndrome of persistent, fluctuating symptoms subsequent to COVID-19 infection with a prevalence global estimate of many millions of cases. LC has significant detrimental effects on health-related quality of life (HRQoL), activities of daily living (ADL), and work productivity. Condition-specific patient-reported outcome measures (PROMs), such as the modified Covid-19 Yorkshire Rehabilitation Scale (C19-YRSm), have been developed to capture the impact of LC. However, these do not provide health utility data required for cost-utility analyses of LC interventions. The aim of this study was therefore to derive a mapping algorithm for the C19-YRSm to enable health utilities to be generated from this PROM. Methods: Data were collected from a large study evaluating LC services in the UK. A total of 1434 people with LC had completed both the C19-YRSm and the EQ-5D-5L on the same day. The EQ-5D-5L responses were then converted to EQ-5D-3L utility scores. Correlation and linear regression analyses were applied to determine items from the C19-YRSm and covariates for inclusion in the algorithm. Model fit, mean differences across the range of EQ-5D-3L scores (-0.59 to 1), and Bland-Altman plots were used to evaluate the algorithm. Responsiveness (standardised response mean; SRM) of the mapped utilities was also investigated on a subset of participants with repeat assessments (N=85). Results: There was a strong level of association between 8 items and 2 domains on the C19-YRSm with the EQ-5D single-item dimensions. These related to joint pain, muscle pain, anxiety, depression, walking/moving around, personal care, ADL, and social role, as well as Overall Health and Other Symptoms. Model fit was good (R2 = 0.7). The mean difference between the actual and mapped scores was < 0.10 for the range from 0 to 1 indicating a good degree of targeting for positive values of the EQ-5D-3L. The SRM for the mapped EQ-5D-3L health utilities (based on the C19-YRSm) was 0.37 compared to 0.17 for the observed EQ-5D-3L utility scores, suggesting the mapped EQ-5D-3L is more responsive to change. Conclusions: We have developed a simple, responsive, and robust mapping algorithm to enable EQ-5D-3L health utilities to be generated from 10 items of the C19-YRSm. This mapping algorithm will facilitate economic evaluations of interventions, treatment, and management of people with LC, as well as further helping to describe and characterise patients with LC irrespective of any treatment and interventions.
{"title":"Health-related quality of life in Long COVID: Mapping the condition-specific C19-YRSm measure onto the EQ-5D-5L","authors":"Adam B. Smith, Darren C. Greenwood, Paul Williams, Joseph Kwon, Stavros Petrou, Mike Horton, Thomas Osborne, Ruairidh Milne, Locomotion Consortium, Manoj Sivan","doi":"10.1101/2024.08.11.24311809","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311809","url":null,"abstract":"Background: Long Covid (LC) is a clinical syndrome of persistent, fluctuating symptoms subsequent to COVID-19 infection with a prevalence global estimate of many millions of cases. LC has significant detrimental effects on health-related quality of life (HRQoL), activities of daily living (ADL), and work productivity. Condition-specific patient-reported outcome measures (PROMs), such as the modified Covid-19 Yorkshire Rehabilitation Scale (C19-YRSm), have been developed to capture the impact of LC. However, these do not provide health utility data required for cost-utility analyses of LC interventions. The aim of this study was therefore to derive a mapping algorithm for the C19-YRSm to enable health utilities to be generated from this PROM. Methods: Data were collected from a large study evaluating LC services in the UK. A total of 1434 people with LC had completed both the C19-YRSm and the EQ-5D-5L on the same day. The EQ-5D-5L responses were then converted to EQ-5D-3L utility scores. Correlation and linear regression analyses were applied to determine items from the C19-YRSm and covariates for inclusion in the algorithm. Model fit, mean differences across the range of EQ-5D-3L scores (-0.59 to 1), and Bland-Altman plots were used to evaluate the algorithm. Responsiveness (standardised response mean; SRM) of the mapped utilities was also investigated on a subset of participants with repeat assessments (N=85). Results: There was a strong level of association between 8 items and 2 domains on the C19-YRSm with the EQ-5D single-item dimensions. These related to joint pain, muscle pain, anxiety, depression, walking/moving around, personal care, ADL, and social role, as well as Overall Health and Other Symptoms. Model fit was good (R2 = 0.7). The mean difference between the actual and mapped scores was < 0.10 for the range from 0 to 1 indicating a good degree of targeting for positive values of the EQ-5D-3L. The SRM for the mapped EQ-5D-3L health utilities (based on the C19-YRSm) was 0.37 compared to 0.17 for the observed EQ-5D-3L utility scores, suggesting the mapped EQ-5D-3L is more responsive to change. Conclusions: We have developed a simple, responsive, and robust mapping algorithm to enable EQ-5D-3L health utilities to be generated from 10 items of the C19-YRSm. This mapping algorithm will facilitate economic evaluations of interventions, treatment, and management of people with LC, as well as further helping to describe and characterise patients with LC irrespective of any treatment and interventions.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"16 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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