bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical and brain frailty in stroke: shared occurrence and outcomes. A cohort study
Authors: Taylor-Rowan M , Hafdi M , Drozdowska B , Elliott E , Wardlaw J , Quinn T 
Published: February 2023

AbstractBackgroundThere is increasing interest in the concept of frailty in stroke, including both physical frailty and imaging-evidence of brain frailty. We aimed to 1)establish concurrent validity of a brain frailty measurement against traditional measures of physical and global frailty 2)establish prevalence of brain frailty in stroke survivors with and without pre-existing frailty 3)establish the predictive validity of measures of physical, global, and brain frailty against long-term cognitive outcomes.MethodsWe included consecutively admitted stroke or transient ischaemic attack (TIA) survivors from participating stroke centres. Baseline CT scans were used to identify leukoaraiosis, atrophy, or old infarcts; these were then combined to generate an overall brain frailty score for each participant on a scale ranging from 0-3 (3=higher brain frailty). Global frailty was measured using Rockwood frailty index, and physical frailty using a Fried frailty screening tool. Presence of major or minor neurocognitive disorder at 18-months following stroke was established via a multicomponent assessment. We assessed the concurrent validity of brain frailty and frailty scales via Spearman’s rank correlation. Prevalence of brain frailty was established based upon observed percentages within groups defined by frailty status (robust, pre-frail, frail). We conducted multivariable logistic regression analyses to evaluate association between brain, global, and physical frailty with 18-month cognitive impairment.ResultsThree-hundred-forty-one stroke survivors participated. Brain frailty was weakly correlated with Rockwood frailty (Rho:0.336;p<0.001) and with Fried frailty (Rho:0.230;p<0.001). Three-quarters of people who were frail had moderate-severe brain frailty and prevalence increased according to frailty status. Brain frailty (OR:1.64,95%CI=1.17-2.32), Rockwood frailty (OR:1.05,95%CI=1.02-1.08) and Fried frailty (OR:1.93,95%CI=1.39-2.67) were each independently predictive of cognitive impairment at 18 months following stroke. Fried frailty was predictive independent of age, sex, stroke severity, education, baseline cognitive test performance, and brain frailty status (OR:1.49,95%CI=1.03-2.18)ConclusionsPhysical and brain frailty are separate concepts, although they frequently co-exist. Both are associated with adverse cognitive outcomes and physical frailty remains important when assessing cognitive outcomes.
Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression
Authors: Koh Youngil , Kim Hyemin , Song Seulki , Choi Young Hoon , Joo So Young , Kim Hyung Rae , Moon Byul , Byun Jamin , Hong Junshik , Shin Dong-Yeop , Park Solip , Lee Kwang Hyuck , Lee Kyu Taek , Lee Jong Kyun , Park Daechan , Jang Jin-Young , Lee Hyunsook , Kim Jung-Ae , Yoon Sung-Soo , Park Joo Kyung 
Published: February 2023

ABSTRACTLysosome is closely linked to autophagy, which plays a vital role in pancreatic adenocarcinoma (PDAC) tumor biology. This study investigated whether lysosome storage dysfunction (LSD) contributes to PDAC development. Germline putative pathogenic variants (PPVs) in genes involved in lysosome functions were compared between PDAC patients (N=418) and healthy controls (N=845). Furthermore,Galc-knockout mouse pancreas organoids and human PDAC organoids were used to evaluate the consequences of PPV status in PDAC development and establishment. LSD PPVs were enriched in PDAC patients (Log2OR=1.65, P=3.08×10−3). PPV carriers diagnosed with PDAC were younger than non-carriers (61.5 vs. 65.3 years, P=0.031). Hampered autophagolysosome activity with increased autophagy flux and elevated Ki-67 index were observed following GALC downregulation. RNA sequencing of human PDAC organoids revealed upregulation of metabolism related to LSD. Genetically defined lysosome dysfunction is frequently observed in young-age onset PDACs. Lysosome dysfunction might contribute to PDAC development via altered metabolism and impaired autophagolysosome activity.
Early postpartum HbA1c after hyperglycemia first detected in pregnancy - imperfect but not without value
Authors: Coetzee Ankia , Hall David R , van de Vyver Mari , Conradie Magda 
Published: February 2023

AbstractBackgroundSouth Africanwomen of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for alternate solutions.AimTo compare the diagnostic performance of HbA1c to the current gold standard OGTT in women with HFDP 4-12 weeks post-delivery.MethodsGlucose homeostasis was assessed with OGTT and HbA1c in 167 women with HFDP, 4-12 weeks after delivery. Glucose status was based on American Diabetes Association criteria.ResultsGlucose homeostasis was assessed at 10 weeks (IQR 7-12) after delivery. A total of 52/167 (31%) participants had hyperglycemia, 34 (20%) had prediabetes, and 18 (11%) had T2DM. For patients with prediabetes, fasting plasma glucose (FPG) and 2 hour plasma glucose (2hPG) were diagnostic in 12 patients, whereas in two-thirds (22/34) only one time point was diagnostic. FPG and 2hPG values were both in the prediabetes diagnostic range in six women with T2DM. Based on FPG, 15 women with persistent hyperglycemia (11 with prediabetes and four with T2DM) would have been missed (15/52; 29%). The HbA1c accurately classified 85% of the 52 participants with gold standard OGTT defined hyperglycemia and 15 of 18 women with postpartum persistent T2DM. When compared to an OGTT, a single HbA1c of 6.5% (48mmol/mol) postpartum demonstrated a sensitivity of 83% and specificity of 97% for the identification of T2DM.ConclusionHbA1c may improve access to postpartum testing in overburdened clinical settings where the required standards of OGTT cannot be guaranteed. HbA1c is a valuable test to detect women who will benefit most from early intervention but cannot unequivocally replace OGTT.
Patients with fibrosis from non-alcoholic steatohepatitis have heterogeneous intrahepatic macrophages and therapeutic targets
Authors: Saldarriaga Omar A. , Krishnan Santhoshi , Wanninger Timothy G. , Oneka Morgan , Rao Arvind , Bao Daniel , Arroyave Esteban , Gosnell Joseph , Kueht Michael , Moghe Akshata , Millian Daniel , Jiao Jingjing , Sanchez Jessica I. , Spratt Heidi , Beretta Laura , Stevenson Heather L. 
Published: February 2023

ABSTRACTBackground and AimsIn clinical trials for reducing fibrosis in NASH patients, therapeutics that target macrophages have had variable results. We evaluated intrahepatic macrophages in patients with non-alcoholic steatohepatitis to determine if fibrosis influenced phenotypes and expression of CCR2 and Galectin-3.Approach & ResultsWe used nCounter to analyze liver biopsies from well-matched patients with minimal (n=12) or advanced (n=12) fibrosis to determine which macrophage-related genes would be significantly different. Known therapy targets (e.g., CCR2 and Galectin-3) were significantly increased in patients with cirrhosis.However, several genes (e.g., CD68, CD16, and CD14) did not show significant differences, and CD163, a marker of pro-fibrotic macrophages was significantly decreased with cirrhosis. Next, we analyzed patients with minimal (n=6) or advanced fibrosis (n=5) using approaches that preserved hepatic architecture by multiplex-staining with anti-CD68, Mac387, CD163, CD14, and CD16. Spectral data were analyzed using deep learning/artificial intelligence to determine percentages and spatial relationships. This approach showed patients with advanced fibrosis had increased CD68+, CD16+, Mac387+, CD163+, and CD16+CD163+ populations. Interaction of CD68+ and Mac387+ populations was significantly increased in patients with cirrhosis and enrichment of these same phenotypes in individuals with minimal fibrosis correlated with poor outcomes. Evaluation of a final set of patients (n=4) also showed heterogenous expression of CD163, CCR2, Galectin-3, and Mac387, and significant differences were not dependent on fibrosis stage or NAFLD activity.ConclusionsApproaches that leave hepatic architecture intact, like multispectral imaging, may be paramount to developing effective treatments for NASH. In addition, understanding individual differences in patients may be required for optimal responses to macrophage-targeting therapies.
Characteristics and Outcomes of Multisystem Inflammatory Syndrome in Children: A Multicenter, Retrospective, Observational Cohort Study in Mexico
Authors: González-García Nadia , Yamazaki-Nakashimada Marco Antonio , Márquez-González Horacio , Miranda-Novales Guadalupe , Neme Díaz Gonzalo Antonio , Prado Duran Sandhi Anel , Velázquez Antonio Luévanos , Castilla-Peon Maria F. , Sánchez Duran Miguel Alejandro , Márquez Aguirre Martha Patricia , Villasis-Keever Miguel Angel , Aragón Nogales Ranferi , Enríquez Carlos Núñez , Martinez Bustamante Maria Elena , Argüello Carlos Aguilar , de los Santos Jesús Ramírez , Pérez Barrera Alejandra , Palacios Cantú Lourdes Anais , Mondragón Jesús Membrila , Alvarado Paloma Vizcarra , Jiménez Juárez Rodolfo Norberto , López Víctor Olivar , Chávez Adrián López 
Published: February 2023

AbstractMultisystem inflammatory syndrome in children temporally associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysm were found in 5.7% and 13.2% of the patients, respectively. The rate of mortality due to SARS-CoV-2-related factors was 4.6%. Delay of ≥10 days in hospital admission was associated with coronary artery aneurysm or dilatation (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2–2.0). Age ≥ 10 years (OR 5.6, 95% CI 1.4–2.04), severe underlying condition (OR 9.3, 95% CI 2.8–31.0), platelet count < 150,000/mm3(OR 4.2, 95% CI 1.2–14.7), international normalized ratio > 1.2 at admission (OR 3.8, 95% CI 1.05–13.9), and serum ferritin concentration > 1500 mg/dL (OR 52, 95% CI 5.9–463) were risk factors for death.
Community and health system factors influencing snake envenomation management practices in three districts of Ghana: a qualitative inquiry from health stakeholders and snakebite victims
Authors: Dzenu Mabel Worlasi , Agani Afaya , Ayanore Martin 
Published: February 2023

AbstractIntroductionSnakebite is a neglected public health issue affecting individuals of all ages in many tropical countries. Venom from snakebite is a potentially life-threatening disease associated with severe morbidities and mortalities. However, literature on snakebite envenoms management practices remains understudied. This study sought to explore community and health system factors influencing snake envenomation management practices in three districts in the Oti region of Ghana. Also, we assessed the current adherence to snakebite treatment protocols to the national and World Health Organization (WHO) recommended protocols.MethodsThe study adopted an exploratory descriptive qualitative study design. Purposive sampling technique was used to recruit participants for the study. The participants included snakebite victims, traditional healers, and health professionals. In-depth interviews and focused group discussions were used to collect data from the participants. All the interviews were audio recorded and transcribed verbatim and exported to Atlas Ti for data management and analyses. The transcribed data were analyzed using the content analysis method to develop the categories for the study findingsFindingsTwenty-six (26) participants were recruited including 16 males and 10 females. The study found three main factors that influenced snake envenomation management practices. These factors included health system factors, community-level factors, and adherence to national and WHO-recommended protocols. The health system factors included the unavailability of anti-snake venom, high-cost ASV, and inadequate or no supply of ASV from Ghana Health Service. The community factors included delay in seeking treatment, transportation, and accessibility challenges, and non-community acceptance facility treatment of snakebites. Almost all the health care professional who provide care for snakebite victims adhered to the WHO recommendations.ConclusionThe evidence adduced from this study could be used by public health practitioners to empower the community by increasing awareness of the prevention of snakebites, first aid, and appropriate treatment-seeking behavior. Culturally appropriate interventions that seek to increase awareness to improve the acceptability of hospital management and sensitize the community for early referral of snakebite victims to the nearest health facility having anti-venom treatment.Authors summaryThe negative responses by the community’s acceptance of the kind of treatment given in the health facilities and the unavailability of Anti-snake Venom (ASV) in the study districts’ health facilities inhibit the management of snakebites.
Emergency and Sequalae Management of Traumatic Dental Injuries: A Quality Assessment of Clinical Practice Guidelines
Authors: Zaror Carlos , Seiffert Andrea , Deana Naira Figueiredo , Espinoza-Espinoza Gerardo , Ata-la-Acevedo Claudia , Diaz Rodrigo , Carrasco-Labra Alonso 
Published: February 2023

ABSTRACTThe prevalence and consequences of traumatic dental injuries (TDI) make them a public health problem. Trustworthy TDI Clinical Practice Guidelines (CPGs) can assist clinicians in making a proper diagnosis, and guide them to the most appropriate therapy for every case. The aim of this study was to identify and evaluate the quality of CPGs for the diagnosis, emergency management and follow-up of TDIs. A systematic search was carried out in MEDLINE, EMBASE, Epistemonikos, Trip database, CPG’ websites, and dental societies to identify documents providing recommendations for the emergency and sequelae management of TDIs. Reviewers assessed the included guidelines independently and in duplicate, using the AGREE II instrument. T-student or ANOVA tests were used to determine the attributes of CPGs associated with the total score in AGREE II. Ten CPGs published between 2010 and 2020 were included, mostly from Europe (n=6). The overall agreement between reviewers was very good (0.94; 95%CI 0.91-0.97). The mean scores for each domain were as follows: Scope and purpose 78.0 ± 18.9%; Stakeholder involvement 46.9 ± 29.6%; Rigour of development 41.8 ± 26.7%; Clarity of presentation 75.8 ± 17.6%; Applicability 15.3 ± 18.8% and Editorial independence 41.7 ± 41.7%. The overall mean rate was 4 ± 1.3 out of a maximum score of 7. Only two guidelines were recommended by the reviewers and rated as high quality. The CPGs developed by governments showed a significantly higher overall score. The overall quality of CPGs on TDI was suboptimal. Therefore, the CPGs developers need to use a methodology that allows them to formulate recommendations in a structured, transparent, and explicit way.
Computed tomography perfusion parameters predictive of symptomatic intracranial hemorrhage after mechanical thrombectomy in patients with cerebral large vessel occlusion
Authors: Abe Soichiro , Inoue Manabu , Shirakawa Manabu , Uchida Kazutaka , Yamada Kiyofumi , Kuramoto Yoji , Namitome Satoshi , Shindo Seigo , Sakakibara Fumihiro , Kouno Junichi , Tatebayashi Kotaro , Kinjo Norito , Tsuji Shoichiro , Tanada Shuichi , Beppu Mikiya , Matsukawa Hidetoshi , Ihara Masafumi , Yoshimura Shinichi 
Published: February 2023

AbstractBackgroundHemorrhagic transformation (HT) after recanalization is a severe complication in patients with a large ischemic core due to cerebral large vessel occlusion. Risk assessment using perfusion imaging to predict hemorrhagic infarction has not been established. Thus, we aimed to investigate the association between perfusion imaging findings and HT in patients with acute cerebral large vessel occlusion who had undergone preoperative perfusion imaging evaluation and mechanical thrombectomy.MethodsWe enrolled consecutive patients who received mechanical thrombectomy (MT) after undergoing perfusion imaging for anterior large vessel occlusion from May 2019 to March 2022. The patients in whom recanalization was not achieved and who experienced procedure-related bleeding were excluded. We investigated the predictors of symptomatic intracranial hemorrhage (sICH) by exploring preoperative perfusion imaging parameters [relative cerebral blood flow, relative cerebral blood volume (rCBV), time of maximum concentration, hypoperfusion index ratio].ResultsAmong the 167 patients (median age 79 years, 47% female) enrolled, 63 (38%) and 14 (8%) patients had any intracranial hemorrhage and sICH (sICH group), respectively. The sICH group had a shorter puncture-recanalization time than the non-sICH group (median [interquartile range (IQR)]; 43 [34–55] vs. 61 [37–88], p = 0.046), whereas the modified Rankin Scale at 90 days showed a worse prognosis (median [IQR]; 5 [5–6] vs 3 [1–4], p<0.01). All perfusion imaging parameters were significantly predicting the sICH group in multiple logistic regression analysis. The value of rCBV was the parameter most strongly associated with sICH in receiver operating characteristic curve analysis (area under the curve = 0.90, 95% confidence interval [0.83–0.98]; cutoff 43 ml; sensitivity, 86 %; specificity, 87%).ConclusionAmong perfusion CT parameters, rCBV is highly associated with sICH after MT for cerebral large vessel occlusion. In patients with low rCBV regions, the indication of mechanical thrombectomy should be carefully considered for postoperative intracranial hemorrhage.Clinical perspectiveOf the various parameters assessed via perfusion CT, the value of rCBV demonstrates a strong correlation with the occurrence of symptomatic intracranial hemorrhage following mechanical thrombectomy for cerebral anterior large vessel occlusion.When treating patients with regions of large low-rCBV, it is important to carefully determine the indication of mechanical due to the potential risk of postoperative intracranial hemorrhage.
Prediction of plasma volume and total hemoglobin mass with machine learning
Authors: Moreillon B. , Krumm B. , Saugy J.J. , Saugy M. , Botrè F. , Vesin J.-M. , Faiss R. 
Published: February 2023

AbstractAnemia is a widespread disease commonly diagnosed through hemoglobin concentration ([Hb]) thresholds set by the World Health Organization (WHO). However, [Hb] is subject to significant variations mainly due to shifts in plasma volume (PV) which impair the diagnosis of anemia and other medical conditions. The aim of this study was to develop a model able to accurately predict total hemoglobin mass (Hbmass) and PV based on anthropometric and complete blood count (CBC) analyses. 769 CBC coupled to measures of Hbmass and PV using the CO-rebreathing method were used with a machine learning tool in a numeric computing platform (MATLAB regression learner app) to calculate the model. For the predicted values, root mean square error (RMSE) was of 37.9 g and 50.0 g for Hbmass, and 194 ml and 268 ml for PV, in women and men, respectively. Measured and predicted data were significantly correlated (p<0.001) with the coefficient of determination (R2) ranging from 0.73 to 0.81 for Hbmass, and PV, in both women and men. The bland-altman bias between estimated and measured variables was in average of -0.69 for Hbmass and 0.73 for PV. This study proposes a valid model with a high prediction potential for Hbmass and PV, providing relevant complementary data in numerous contexts. This method can notably bring information applicable to the epidemiology of anemia, particularly in countries with high prevalence or in specific population such as high-altitude communities.
Tempo-spatial dynamics of COVID-19 in Germany – A phase model based on a pandemic severity indicator
Authors: Stabler Martin , Kuebart Andreas 
Published: February 2023

AbstractWhile pandemic waves are often analyzed on the national scale, they typically are not distributed evenly in space. This working paper employs a novel approach to analyze the tempo-spatial dynamics of the COVID-19 pandemic for the case of Germany. First, we base the analysis not just on the incidence of cases or mortality but employ a composite indicator of pandemic severity to gain a more robust understanding of the temporal dynamics of the pandemic. Second, we subdivide the pandemic during the years 0f 2020 and 2021 into fifteen phases, each with a coherent trend of pandemic severity. Third, we analyze the spatial patterns predominating in each phase. The resulting tempo-spatial phase model is used to identify explanatory factors for the tempo-spatial patterns identified in the analysis.DisclosuresThis work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) with a research grant for the project Socio-spatial diffusion of COVID-19 in Germany. - 492338717
Detection of HypervirulentKlebsiella pneumoniaefrom Clinical Samples in Tamil Nadu
Authors: Shanthini Thamaraiselvan , Manohar Prasanth , Hua Xiaoting , Leptihn Sebastian , Nachimuthu Ramesh 
Published: February 2023

AbstractKlebsiellapneumoniae is one of the significant opportunistic pathogens which cause both nosocomial and community-acquired infections. This study focuses on the molecular characterization of hypervirulentK. pneumoniaeisolated from clinical samples in Tamil Nadu. A total of 30 clinicalK. pneumoniaeisolates were collected from the diagnostic centres located in Trichy, Madurai, and Chennai. On subjected to the antibiotic susceptibility testing, it was found that 73% were multi-drug resistant. The string test showed that 46.6% of the isolates were hypermucoviscous (HMV). Molecular studies revealed the absence ofmcr (1-5)genes. The isolates belonging to capsular types K1 (n=5), K2 (n=6) and K5 (n=2) were detected. Virulence genes namelyrmpA(n=5), aerobactin (n=8), andKfuBC(n=8) were identified using multiplex polymerase chain reaction. Through molecular studies, 22 isolates were found to be classicalK. pneumoniae(cKP) and 8 were hypervirulentK. pneumoniae(hvKP). The genome sequencing of five isolates revealed that the strains belong to ST86 and ST23.In vivostudies usingGalleria mellonellashowed that HMV-hvKP strains were highly pathogenic among the hvKP strains and the non-K1/K2 and K2 strains were pathogenic among the cKP strains. Our data revealed the emergence of colistin-resistant hvKP strains in Tamil Nadu, India.