bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key determinants of the dual clamp/activator function of Complexin
Authors: Makke Mazen , Ruiz Alejandro Pastor , Yarzagaray Antonio , Gaya Surya , Zimmer Michelle , Frisch Walentina , Bruns Dieter 
Published: October 2023

AbstractComplexin determines magnitude and kinetics of synchronized secretion, but the underlying molecular mechanisms remained unclear. Here, we show that the hydrophobic face of the amphipathic helix at the C-terminus of Complexin II (CpxII, amino acids 115- 134) binds to fusion-promoting SNARE proteins, prevents premature secretion and allows vesicles to accumulate in a release-ready state. Specifically, we demonstrate that an unrelated amphipathic helix functionally substitutes for the CTD of CpxII and that amino acid substitutions on the hydrophobic side compromise the arrest of the prefusion intermediate. To facilitate synchronous vesicle fusion, the N-terminal domain (NTD) of CpxII (amino acids 1-27) specifically cooperates with synaptotagmin I (SytI), but not with synaptotagmin VII. Expression of CpxII rescues the slow release kinetics of the Ca2+- binding mutant Syt I R233Q, whereas the N-terminally truncated variant of CpxII further delays it. These results indicate that the CpxII NTD regulates mechanisms which are governed by the forward rate of Ca2+binding to Syt I. Overall, our results shed new light on key molecular properties of CpxII that hinder premature exocytosis and accelerate synchronous exocytosis.
Detecting Cerebral Ischemia from Electroencephalography During Carotid Endarterectomy Using Machine Learning
Authors: Mina Amir I. , Espino Jessi U. , Bradley Allison M. , Thirumala Parthasarathy D. , Batmanghelich Kayhan , Visweswaran Shyam 
Published: October 2023

AbstractIntraoperative stroke is a major concern during high-risk surgical procedures such as carotid endarterectomy (CEA). Ischemia, a stroke precursor, can be detected using continuous electroencephalographic (cEEG) monitoring of electrical changes caused by changes in cerebral blood flow. However, monitoring by experts is currently resource-intensive and prone to error. We investigated if supervised machine learning (ML) could detect ischemia accurately using intraoperative cEEG. Using cEEG recordings from 802 patients, we trained six ML models, including naïve Bayes, logistic regression, support vector classifier, random forest (RF), light gradient-boosting machine (LGBM), and eXtreme Gradient Boosting with random forest (XGBoost RF), and tested them on a validation dataset of 30 patients. Each cEEG recording in the validation dataset was labeled independently by five expert neurophysiologists who regularly perform intraoperative neuromonitoring. We did not derive consensus labels but rather evaluated an ML model in a pairwise fashion using one expert as a reference at a time, due to the experts’ variability in label determination, which is typical for clinical tasks. The tree-based ML models, including RF, LGBM, and XGBoost RF, performed best, with AUROC values ranging from 0.92 to 0.93 and AUPRC values ranging from 0.79 to 0.83. Our findings suggest that ML models can serve as the foundation for a real-time intraoperative monitoring system that can assist the neurophysiologist in monitoring patients.
Exploring the potential of a saliva-based, RNA-extraction-free PCR test for the multiplexed detection of key respiratory pathogens
Authors: Allicock Orchid M. , Lin Tzu-Yi , Fajardo Katherine T. , Yolda-Carr Devyn , Hislop Maikel S. , Wang Jianhui , Zuniga Denora , Platt William , Tuohy Beth , Wyllie Anne L. 
Published: October 2023

ABSTRACTIntroductionEfforts to diagnose and monitor transmissible respiratory infections can be impaired by invasive or resource-intensive sample collection. Having extensively demonstrated the feasibility of saliva for SARS-CoV-2 detection, we sought to validate its potential for other common upper respiratory tract pathogens.MethodsWe modified our RNA-extraction-free SARS-CoV-2 PCR test for multiplexed detection of influenza A/B (IAV/IBV), respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Stability of virus detection in saliva from virus-positive patients was tested after storage at +4°C, room temperature (∼19°C), 30°C and 40°C for up to 7 days and through simulated shipping conditions. De-identified saliva samples were collected from individuals (≥18 years) with respiratory symptoms who were undergoing nasal-swab-based testing for SARS-CoV-2 (New Haven, CT). Saliva samples from SARS-CoV-2-negative individuals were tested with the multiplexed assay, with and without RNA extraction.ResultsThe limit of assay detection ranged from 3-6 copies/μl, virus target depending. Detection remained stable after prolonged sample storage at elevated temperatures and through shipping conditions. From the symptomatic testing sites, 1,095 clinical specimens tested SARS-CoV-2-negative. Upon multiplexed testing of their paired saliva, 41 (3.7%) tested positive (IAV, n=20; RSV, n=5; hMPV, n=7). Additionally, upon screening samples in singleplex for pneumococcus, 29 (3%) samples tested positive.ConclusionOur findings emphasize the adaptability of a low-cost, open-source saliva-based PCR test for common respiratory pathogens, beyond SARS-CoV-2. We demonstrated its utility in symptomatic individuals, identifying viral infection missed when testing focused solely on a singular target, such as SARS-CoV-2.
Characterizing Potential Interaction Between Respiratory Syncytial Virus and Seasonal Influenza in the U.S.
Authors: Chen Jiani , Gokhale Deven V. , Liu Liang , Rohani Pejman , Bahl Justin 
Published: October 2023

AbstractRSV and seasonal influenza are two of the most important causes of respiratory infection that consistently peak during winter months in the U.S. Here, we characterized the circulation of these viruses in the U.S. with weekly positive case reports and genetic surveillance and used a mathematical modeling approach to explore their potential interaction at an HHS regional level. Our analyses showed RSV and seasonal influenza co-circulate with various relatively epidemic sizes and seasonal overlaps across seasons and regions. We found RSV might have different evolutionary dynamics compared to seasonal influenza, with local persistence may play a role in underlying annual epidemics. Our analysis supports a competitive interaction between RSV and seasonal influenza in most HHS regions and we speculate that cross-immunity after infection might be the major driver of viral competition. Together, our work supports the competition between RSV and seasonal influenza across the U.S. at a population level. Our findings are important for the future development of protective strategies against these respiratory viruses.
Leprosy campaigns in Brazil: analysis of "Janeiro Roxo" impact using Google Trends.
Authors: VASCONCELLOS-SILVA PAULO ROBERTO , DE SOUSA ARTUR CUSTÓDIO MOREIRA 
Published: October 2023

“Janeiro Roxo” (Purple January) is a Brazilian campaign to raise awareness about leprosy and its early symptoms. The negative influence of the COVID-19 pandemic on institutional campaigns was especially relevant for the control of leprosy, if considered its status of neglected disease by the media. Google Trends (GT) is a free tool that tracks accesses to given terms on Google. Using GT we studied (i) impact of “Janeiro Roxo” in public interest on leprosy in the last 5 years; (ii) public interest during and after COVID-19 pandemic; (iii) patterns of public interest in self-identification of leprosy signs. Methods: GT tracking follows the popularity of topics in time range in “Relative Search Volume” (RSV) – proxies of public interest in a particular subject on a scale from 0 to 100. We selected “HANSENÍASE” (HAN) and “HANSENÍASE SINTOMAS” (leprosy symptoms) (H.SIN) to estimate public interest in leprosy and “self-diagnosis” during 261 weeks (August 2018 to 2023). Polynomial trend lines estimate trends over the period. Weekly RSV, monthly and annual means were compared using Analysis of Variance (ANOVA). Results: In 261 weeks: higher RSV to “HANSENÍASE” (HAN) compared to “HANSENÍASE SINTOMAS” (H.SIN); highest Monthly Means (MM) in January months (2019 to 2023) for both HAN and H.SIN. Pandemic effect in “Janeiro Roxo”: decrease in January MM 2021 compared to 2020 (24% to HAN, 25% to H.SIN). Both HAN/H.SIN reached pre-pandemic levels in January 2022/2023. Breakpoints (points of abrupt change which influences trend lines) in the 26th week (February 2019); in the 55th and 213th week (September 2019 and 2022). Trend line (HAN): upward curve between 33rd-45th week (April to June 2019); pandemic downward trend between 120th-136th week (December 2020 to March 2021); upward trend curve between 220th-240th week (November 2022 to March 2023). Conclusion: “Janeiro Roxo” and in-person activities, among other media stimuli, have a relevant impact in terms of public interest in leprosy, even after their interruption due to pandemic. Considering their impacts on national searches, regional campaigns should be considered very successful. RSV to HAN may be due to “reactive searches” motivated by transient stimuli from campaigns, in an ephemeral and impersonal way. “Proactive searches” to H.SIN may be associated to those interested - in a personal way - in early symptoms and self-diagnosis. Internet-based campaign evaluation programs could be useful in integrating vulnerable regions and exposing their needs for assistance services.
The α2A-adrenergic receptor (ADRA2A) modulates susceptibility to Raynaud’s syndrome
Authors: Tervi Anniina , Ramste Markus , Abner Erik , Cheng Paul , Lane Jacqueline M. , Maher Matthew , Lammi Vilma , Strausz Satu , Nguyen Trieu , Docampo Mauro Lago , Gu Wenduo ,   FinnGen, Estonian biobank research team, Esko Tõnu , Saxena Richa , Palotie Aarno , Ripatti Samuli , Sinnott-Armstrong Nasa , Daly Mark , Rabinovitch Marlene , Heckman Caroline A. , Quertermous Thomas , Jones Samuel E. , Ollila Hanna M. 
Published: October 2023

AbstractRaynaud’s syndrome is a common dysautonomia where exposure to cold increases the vascular tone of distal arteries causing vasoconstriction and hypoxia, particularly in the extremities. Current treatment options are limited and unspecific. Biological mechanisms leading to the phenotype remain uncharacterized. Using genetic and electronic health record data from the UK Biobank, the Mass-General Brigham Biobank, the Estonian Biobank, and the FinnGen study, we identified 11,358 individuals with a diagnosis of Raynaud’s syndrome and 1,106,871 population controls. We found eight loci including endothelial nitric oxide synthase (NOS3), HLA, and a notable association at the α2A-adrenergic receptor (ADRA2A)locus (rs7090046, P = 3.93×10-47), implicating adrenergic signaling as a major risk factor with Raynaud’s syndrome. We further investigate the role of the variants andADRA2Aexpression in functional and physiological models.In silicofollow-up analysis revealed an expression quantitative trait locus (eQTL) that co-localized and increasedADRA2Agene expression in a tissue-specific manner in the distal arteries. Staining with RNA scope further clarified the specificity ofADRA2Aexpression in small vessels. We show by CRISPR gene editing that the SNP region modifiesADRA2Agene expression in pulmonary artery smooth muscle cells. Finally, we performed a functional contraction assay on smooth muscle cells in cold conditions and showed lower contraction inADRA2A-deficient and higher contraction inADRA2A-overexpressing smooth muscle cells. Our results indicate that Raynaud’s syndrome is related to vascular function mediated by adrenergic signaling throughADRA2A. Our study highlights the power of genome-wide association testing as a discovery tool for poorly understood clinical endpoints and further clarifies the role of adrenergic signaling in Raynaud’s syndrome by fine-mapping, usingin vitrogenomic manipulations and functional validation in distal smooth muscle cell populations located in arterioles
Explainable artificial intelligence for cough-related quality of life impairment prediction in asthmatic patients
Authors: Narteni Sara , Baiardini Ilaria , Braido Fulvio , Mongelli Maurizio 
Published: October 2023

AbstractExplainable Artificial Intelligence (XAI) is becoming a disruptive trend in healthcare, allowing for transparency and interpretability of autonomous decision-making. In this study, we present an innovative application of a rule-based classification model to identify the main causes of chronic cough-related quality of life (QoL) impairment in a cohort of asthmatic patients. The proposed approach first involves the design of a suitable symptoms questionnaire and the subsequent analyses via XAI. Specifically, feature ranking, derived from statistically validated decision rules, helped in automatically identifying the main factors influencing an impaired QoL: pharynx/larynx and upper airways when asthma is under control, and asthma itself and digestive trait when asthma is not controlled. Moreover, the obtainedif-thenrules identified specific thresholds on the symptoms associated to the impaired QoL. These results, by finding priorities among symptoms, may prove helpful in supporting physicians in the choice of the most adequate diagnostic/therapeutic plan.
ASSESSMENT OF THE BACTERIOLOGICAL QUALITIES OF MEAT AND CONTACT SURFACES IN MARKETS IN ABIA STATE, NIGERIA
Authors: Iwuagwu Uchechukwu Olive , Amadi Agwu Nkwa , Nworuh Blessed Okwuchi , Iwuala Chimezie Christian , Innocent David Chinaecherem , Ikeanumba Michael Okwudiri , Okorie Mary Onyinyechi 
Published: October 2023

ABSTRACTBackgroundMicrobial contamination of meat comes from external sources during cutting, handling and processing of the meat. This study was carried out to assess the bacteriological qualities of meat and contact surfaces in markets in Abia State, Nigeria.MethodsThis research involved the use of a Hazard Analysis Critical Control Point (HACCP) checklist to investigate the sanitation and hygiene practices of meat sellers and a laboratory study of red and white meat, water and meat-contact surface samples. A total of 425 meat samples collected from 425 meat sellers from some randomly selected markets in Abia State were used for the study. There were also 20 water samples, 22 samples from table surfaces, 22 samples from knife surfaces and 14 samples from transport vehicles. The multistage simple random sampling technique through balloting was employed to determine communities/markets for the study. Samples for the study were collected and analyzed using standard microbiological techniques such as culturing and the bacteria were enumerated and identified using biochemical and chemical tests.ResultsThe prevalent bacterial isolates includeStaphylococcussp (78.80%),Bacillussp (73.17%),Enterococcussp (64.00%),Escherichia coli(62.11%),Salmonellasp (62.11%),Klebsiellasp (51.29%),Micrococcus sp(44.94%) andCampylobactersp (43.52%). SPSS analysis using the one way ANOVA showed no significant difference (P>0.05) in bacteria isolated from markets in the three Senatorial Zones of the State.Staphylococcussp was isolated in 61.11% of the tables, 50.00% of vehicles, 41.67% of knives and 46.32% of water;Salmonellasp was isolated in 47.22% of the tables, 36.11% of vehicles, 30.56% of knives and 43.85% of water;Bacillussp was isolated in 41.67% of the tables, 44.44% of vehicles, 33.33% of knives and 23.70% of water;Campylobactersp was isolated in 27.78% of the tables, 25.00% of vehicles, 30.56% of knives and none in water. There was no significant difference (P>0.05) in bacteria isolated from the contact surfaces and water from the markets in the three zones of the State.ConclusionThe bacteriological quality of meat in markets in Abia State could be said to be poor due to the isolation of Indicator bacteria such asE, coli, Salmonella and Campylobacterfrom the studied meat samples. The presence ofE. coliin the studied meat samples is an indicator of feacal contamination and a red alert for the Public health sector. It is recommended that meat sellers undergo proper training and regularly update their knowledge of meat safety.
Prevalence of polymyxin resistant bacterial strains in India: a systematic review and meta-analysis
Authors: Dwibedy Sambit K. , Padhy Indira , Panda Aditya K. , Mohapatra Saswat S. 
Published: October 2023

AbstractIntroductionPolymyxins, the cationic lipopeptide antibiotics, are the last line of therapeutics against the MDR Gram-negative bacterial (GNB) pathogens. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted their utility. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are largely understood, the prevalence of PolRstrains in India has not been investigated systematically. The current study was undertaken to primarily determine the prevalence of PolRstrains in India. Moreover, the extent of the spread of mobile colistin resistance (mcr) genes among the GNB strains in India was also determined.MethodA systematic search for articles using the relevant inclusion and exclusion criteria was performed in the applicable databases for the period January 2015 to December 2023. The included 41 studies were subjected to a meta-analysis using the Comprehensive Meta-Analysis software (V.4). Publication biases were assessed using funnel plots and Egger’s regression analysis.ResultConsidering a total of 41 studies including 24,589 bacterial isolates the present meta-analysis found the rate of PolRbacteria in India to be at 15.0% (95% CI: 11.2 to 19.8). Among the Indian States, Tamil Nadu topped with the highest prevalence of PolRat 28.3%. Investigating the contribution of themcrgenes, it was observed that among the PolRstrains, 8.4% (95% CI: 4.8 to 14.3) weremcrpositive.ConclusionThe study determined the prevalence of PolRstrains in India at 15.0% which is higher than that of the global average at 10%. The study also determined that 8.4% of the PolRstrains carried themcrgenes. Themcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion ofmcrscreening in many previous studies. This study provides insight into the state of the PolRsituation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the efficacy of the polymyxins.
Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms
Authors: Almulla Abbas F. , Maes Michael , Zhou Bo , Al-Hakeim Hussein K. , Vojdani Aristo 
Published: October 2023

AbstractBackgroundAutoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).ObjectivesTo examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α+β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B.MethodsIgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof.ResultsLong COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7% of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r=0.801.ConclusionBrain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.
Cerebrovascular Lesion Loads and Accelerated Brain Ageing: Insights into the Cognitive Spectrum
Authors: Beheshti Iman , Potvin Olivier , Dadar Mahsa , Duchesne Simon ,   the CCNA Group
Published: October 2023

ABSTRACTINTRODUCTIONWhite matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimer’s disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain age, which reflects global brain health, and cerebrovascular lesion load in the context of pathological aging in diverse forms of clinically-defined neurodegenerative conditions.METHODSWe computed brain-predicted age difference (brain-PAD: predicted brain age minus chronological age) in the Comprehensive Assessment of Neurodegeneration and Dementia cohort of the Canadian Consortium on Neurodegeneration in Aging including 70 cognitively intact elderly (CIE), 173 MCI, 88 V-MCI, 50 AD, and 47 V-AD using T1-weighted magnetic resonance imaging (MRI) scans. We used a well-established automated methodology that leveraged fluid attenuated inversion recovery MRIs for precise quantification of WMH burden. Additionally, cerebral microbleeds were detected utilizing a validated segmentation tool based on the ResNet50 network, utilizing routine T1-weighted, T2-weighted, and T2* MRI scans.RESULTSThe mean brain-PAD in the CIE cohort was around zero, whereas the four categories showed a significantly higher mean brain-PAD compared to CIE. The brain-PAD was significantly correlated with WMHs in all groups.DISCUSSIONWMHs were associated with faster brain ageing and should be considered as a risk factor which imperils brain health in aging and exacerbate brain abnormalities in the context of neurodegeneration of presumed AD origin. Our findings underscore the significance of novel research endeavors aimed at elucidating the etiology, prevention, and treatment of WMH in the area of brain ageing.HighlightsWe assessed the association between brain-PAD and cerebrovascular lesion loads in aging and AD.There were noticeably links between brain-PAD and WMH loads.The structure of the ageing brain is associated with WMHs.WMH needs to be taken into account as a risk factor that increase the brain age in aging and AD.