bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment and interventional parameters predict excellent recanalization of large vessel occlusion in patients with acute ischemic stroke
Authors: Yedavalli Vivek , Koneru Manisha , Hoseinyazdi Meisam , Greene Cynthia , Copeland Karen , Xu Risheng , Luna Licia , Caplan Justin , Dmytriw Adam , Guenego Adrien , Heit Jeremy , Albers Gregory , Wintermark Max , Gonzalez Fernando , Urrutia Victor , Huang Judy , Leigh Richard , Marsh Elisabeth , Llinas Rafael , Hillis Argye , Nael Kambiz 
Published: August 2023

AbstractBackgroundIn patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO), improved functional outcomes have been reported in patients who achieve Modified Thrombolysis In Cerebral Infarction (mTICI) 2c/3 (excellent recanalization) over mTICI 2b. We aimed to determine pretreatment and interventional variables that could predict achieving mTICI 2c/3 over 2b reperfusion in patients who underwent technically successful mechanical thrombectomy (MT).MethodsIn this retrospective study, consecutive AIS patients with anterior circulation LVO who underwent MT and achieved recanalization with mTICI 2b/2c/3 were included. We evaluated the association between pretreatment clinical and imaging variables and interventional parameters in patients who achieved mTICI 2c/3 vs. 2b using logistic regression and ROC analyses.ResultsFrom 5/11/2019 to 10/09/2022, 149 consecutive patients met our inclusion criteria (median 70 years old [IQR 65 - 78.5], 57.7% female). Adjusted multivariate regression analyses showed that patients with excellent recanalization had lower admission NIHSS (aOR 0.93, p = 0.036), were less likely to have a history of diabetes mellitus (DM) (aOR 0.42, p = 0.050) and prior stroke (aOR 0.27, p = 0.007), had a cerebral blood volume (CBV) index >= 0.7 (aOR 3.75, p = 0.007), and were more likely to achieve excellent recanalization with aspiration alone (aOR 2.89, p = 0.012). A multivariate logistic regression model comprising these independent factors predicted mTICI 2c/3 with an AUC 0.79 (95% CI: 0.68-0.86; p < 0.001), sensitivity of 94%; specificity of 41%.ConclusionRobust collateral status (CS) defined by CBV index >= 0.7, absence of DM and prior stroke, lower initial stroke severity, and direct aspiration are all predictive of excellent recanalization in successfully recanalized AIS-LVO patients. Our findings highlight the prognostic implications of robust CS, DM and stroke prevention, as well as use of aspiration alone in maximizing the likelihood of excellent recanalization.
Global Longitudinal Active Strain Energy Density (GLASED): Age and Sex Differences in young and Veteran Athletes
Authors: MacIver David H. , Zhang Henggui , Johnson Christopher , Papatheodorou Efstathios , Parry-Williams Gemma , Sharma Sanjay , Oxborough David 
Published: August 2023

AbstractAbstract FigureGraphic abstractClinical perspectiveGlobal longitudinal active strain energy density (GLASED) is a recently introduced potential measure of ventricular function that combines myocardial stress and strain information. GLASED estimates the work performed per unit volume of myocardium during contraction. Recent studies with cardiac MRI have demonstrated that GLASED predicts prognosis more accurately than ejection fraction or strain alone. Our current study uses echocardiography and reveals previously unknown physiological differences in myocardial function between male and female athletes, as well as among young and veteran athletes. Our results suggest that GLASED could be a valuable tool in assessing cardiac diseases, particularly when the clinical phenotype is uncertainBackgroundGlobal longitudinal active strain energy density (GLASED) is an innovative method for assessing myocardial function by quantifying the work performed by the left ventricular muscle. The use of GLASED holds promise for improving the diagnosis and management of cardiac diseases. This study aimed to evaluate the feasibility of measuring GLASED using echocardiography and investigate potential differences in GLASED values among athletes based on age and sex.Methods and ResultsAn observational echocardiographic study was conducted, involving male controls, male and female young athletes, and male and female veteran athletes. GLASED was calculated from the myocardial stress and strain. The mean age (years) of young athletes was 21.6 for males and 21.4 for females, while the mean age of veteran athletes was 53.5 for males and 54.2 for females. GLASED was found to be highest in young male athletes (2.40 kJ/m3) and lowest in female veterans (1.96 kJ/m3). Veteran males exhibited lower values (1.96 kJ/m3) compared to young male athletes (P<0.001). Young females demonstrated greater GLASED (2.28 kJ/m3) than veteran females (P<0.01). However, no significant difference in GLASED was observed between male and female veterans.ConclusionsOur findings demonstrate the feasibility of measuring GLASED using echocardiography. GLASED values were higher in young male athletes compared to female athletes, and it decreased with age. Importantly, the sex-related differences observed in GLASED values among young athletes were no longer present in veteran athletes. Estimating GLASED may serve as a valuable screening tool for cardiac diseases in athletes, particularly for those with borderline phenotypes of hypertrophic and dilated cardiomyopathies.
Caspase-2 protects against ferroptotic cell death
Authors: Dawar Swati , Benitez Mariana C. , Lim Yoon , Dite Toby A. , Yousef Jumana M. , Thio Niko , Garciaz Sylvain , Jackson Thomas D. , Milne Julia V. , Dagley Laura F. , Phillips Wayne A. , Kumar Sharad , Clemons Nicholas J. 
Published: August 2023

AbstractCaspase-2, one of the most evolutionarily conserved member of the caspase family, is an important regulator of the cellular response to oxidative stress. Given that ferroptosis is suppressed by antioxidant defense pathways, such as that involving selenoenzyme glutathione peroxidase 4 (GPX4), we hypothesised that caspase-2 may play a role in regulating ferroptosis. This study provides the first demonstration of an important and unprecedented function of caspase-2 in protecting cancer cells from undergoing ferroptotic cell death. Specifically, we show that depletion of caspase-2 leads to downregulation of stress response genes includingSESN2, HMOX1, SLC7A11and sensitises mutant-p53 cancer cells to cell death induced by various ferroptosis inducing compounds. Importantly, the canonical catalytic activity of caspase-2 is not required for its role and suggests that caspase-2 regulates ferroptosis via non-proteolytic interaction with other proteins. Using an unbiased BioID proteomics screen, we identified novel caspase-2 interacting proteins (including heat shock proteins and co-chaperones) that regulate cellular responses to stress. Finally, we demonstrate that caspase-2 limits chaperone mediated autophagic degradation of GPX4 to promote survival of mutant-p53 cancer cells. In conclusion, we document a novel role for caspase-2 as a negative regulator of ferroptosis in cells with mutant-p53. Our results provide evidence for a novel function of caspase-2 functions in cell death regulation and open potential new avenues to exploit ferroptosis in cancer therapy.
Recurrent SARS-CoV-2 mutations at Spike D796 evade antibodies from pre-Omicron convalescent and vaccinated subjects
Authors: Elko Evan A , Mead Heather L , Nelson Georgia A , Zaia John A , Ladner Jason T , Altin John A 
Published: August 2023

AbstractSARS-CoV-2 lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the Receptor Binding Domain, Omicron features amino acid mutations elsewhere in the Spike protein, however their effects generally remain ill-defined. The Spike D796Y substitution is present in all Omicron sub-variants and occurs at the same site as a mutation (D796H) selected during viral evolution in a chronically-infected patient. Here we map antibody reactivity to a linear epitope in the Spike protein overlapping position 796. We show that antibodies binding this region arise in pre-Omicron SARS-CoV-2 convalescent and vaccinated subjects, but that both D796Y and D796H abrogate their binding. These results suggest that D796Y contributes to the fitness of Omicron in hosts with pre-existing immunity to other variants of SARS-CoV-2 by evading antibodies targeting this site.
Migrant men and HIV care engagement in Johannesburg, South Africa
Authors: Nardell Maria F. , Govathson Caroline , Mngadi-Ncube Sithabile , Ngcobo Nkosinathi , Letswalo Daniel , Lurie Mark , Miot Jacqui , Long Lawrence , Katz Ingrid T. , Pascoe Sophie 
Published: August 2023

AbstractBackgroundSouth Africa (SA) has one of the highest rates of migration on the continent, largely comprised of men seeking labor opportunities in urban centers. Migrant men are at risk for challenges engaging in HIV care. However, rates of HIV and patterns of healthcare engagement among migrant men in urban Johannesburg are poorly understood.MethodsWe analyzed data from 150 adult men (≥18 years) recruited in 10/2020-11/2020 at one of five sites in Johannesburg, Gauteng Province, SA where migrants typically gather for work, shelter, transit, or leisure: a factory, building materials store, homeless shelter, taxi rank, and public park. Participants were surveyed to assess migration factors (e.g., birth location, residency status), self-reported HIV status, and use and knowledge of HIV and general health services. Proportions were calculated with descriptive statistics. Associations between migration factors and health outcomes were examined with Fisher exact tests and logistic regression models. Internal migrants, who travel within the country, were defined as South African men born outside Gauteng Province. International migrants were defined as men born outside SA.ResultsTwo fifths (60/150, 40%) of participants were internal migrants and one fifth (33/150, 22%) were international migrants. More internal migrants reported living with HIV than men born in Gauteng (20% vs 6%, p=0.042), though in a multi-variate analysis controlling for age, being an internal migrant was not a significant predictor of self-reported HIV positive status. Over 90% all participants had undergone an HIV test in their lifetime. Less than 20% of all participants had heard of pre-exposure prophylaxis (PrEP), with only 12% international migrants having familiarity with PrEP. Over twice as many individuals without permanent residency or citizenship reported “never visiting a health facility,” as compared to citizens/permanent residents (28.6% vs. 10.6%, p=0.076).ConclusionsOur study revealed a high proportion of migrants within our community-based sample of men and demonstrated a need for bringing PrEP awareness and services to migrants in Johannesburg. Future research is warranted to further disaggregate this heterogenous population by different dimensions of mobility and to understand how to design HIV programs in ways that will address migrants’ challenges.
Risk Factors for Post-Traumatic Stress Disorder (PTSD) in COVID Survivors: A Cross-Sectional Study
Authors: Dhakal Surakshaya , Khatiwada Ram Prasad 
Published: August 2023

ABSTRACTThe study aimed to investigate the impact of demographic, socio-economic, health, and lifestyle variables on the development of PTSD symptoms in COVID survivors. The study used a cross-sectional design, and data were collected via a standard set of questionnaires from 228 COVID survivors, who required oxygen support and were admitted to Damak COVID hospital from April to October 2021.Descriptive statistics such as frequency and percentage were used to summarize the data and inferential statistics such as chi-square test, Fisher’s exact test, and Binary logistic regression were used to analyze the data and to infer the overall result from the taken sample. The study found that only three variables, i.e., gender, diabetes, and chronic obstructive pulmonary disorder (COPD), were significant factors that posed a higher threat of PTSD in COVID survivors. Additionally, the study uses model adequacy tests such as Pseudo R2 test, Reliability test and Hosmer and Lemeshow test to validate the model fitted.The study found that only three variables had significant impact PTSD symptoms in COVID survivors. Male patients were more likely to have PTSD symptoms than female patients. The presence of diabetes before or after the infection increased the risk of PTSD. The patients with high blood pressure before COVID and those who developed chronic obstructive pulmonary disorder (COPD) after COVID were more likely to experience PTSD symptoms. The study provides valuable information on the risk factors for developing PTSD symptoms in COVID survivors. This study can contribute to the understanding and growing body of research on the psychological impact of COVID and help healthcare professionals identify patients who are at risk of developing PTSD and provide them with appropriate interventions to prevent or treat PTSD.
Mortality risk in infants receiving therapeutic care for malnutrition: A secondary analysis
Authors: Mahmud Imteaz , Guesdon Benjamin , Kerac Marko , Grijalva-Eternod Carlos S. 
Published: August 2023

AbstractBackgroundSmall and nutritionally at-risk infants aged <6 months are at high risk of death, but important evidence gaps exist on how to best identify them. We aimed to determine associations between anthropometric deficits and mortality among infants <6m admitted to inpatient therapeutic care.MethodsA secondary analysis of 2002-2008 data included 5,034 infants aged <6m from 12 countries. The prevalence, concurrence, and severity of wasted, stunted, underweight, and the Composite Index of Anthropometric Failure (CIAF) were analysed. We used logistic regression to examine the association of different anthropometric deficits with in-programme mortality.ResultsAmong 3,692 infants aged <6m with complete data, 3,539 (95.8%) were underweight, 3,058 (82.8%) were wasted, 2,875 (77.8%) were stunted, and 3,575 (96.8%) had CIAF. Infants with multiple anthropometric deficits were more severely wasted, stunted, and underweight. A total of 141 infants died during inpatient therapeutic care. Among these, severely wasted (116) and severely underweight (138) infants had higher odds of mortality than normal infants (OR=2.1, 95% CI: 1.2-2.7, p=0.009, and OR=3.3, 95% CI: 0.8-13.6, p=0.09, respectively). Boys had higher odds of inpatient mortality than girls (OR=1.40, 95% CI: 1.02-1.92, p=0.03).ConclusionMultiple anthropometric deficits (CIAF) is common among infants <6m. Future work needs to explore which are the most useful indicator for programme admission and in-programme prognosis: our data supports both WLZ and WAZ, but future work which better accounts for admission bias is urgently needed. Boys appear to be most at-risk. Programmes should ensure that all infants receive timely, evidence-based, effective care.
New Admissions and Asymptomatic TB Cases fuel TB Epidemic in Prisons, a Cross Sectional Survey in Tanzania
Authors: Mangu Chacha David , Clowes Petra , van den Hombergh Jan , Mwakabenga Clement , Mwanyonga Simeon , Ambindwile Jane , Kayombo Faith , Minja Monica , Kalluvya Samuel , Gerwing-Adima Lisa , Kasang Christa , Mueller Andreas , Chilolo Edward , Angolwisye Juma , Nsajigwa Dickson , Kachima Adili , Kamala Deus , Mutayobya Beatrice , Ntinginya Nyanda Elias , Hoelscher Michael , Saathoff Elmar , Rachow Andrea 
Published: August 2023

ABSTRACTBackgroundThere is an increased risk for tuberculosis (TB) infection and disease progression in prison settings. TB prevalence in prisons of high and middle/low income countries have been measured to be between 5 and 50 -times higher than in the general population.MethodsWe performed TB active case finding in five central prisons, Keko, Segerea, Ukonga, Butimba and Ruanda prison in Tanzania, using the Xpert MTB/RIF®assay on early morning or spot sputum sample from inmates and new entries between April 2014 and July 2015.ResultsOut of 13,868 prisoners tested, 13,763 had valid results. TB prevalence was 1.55% (214/13,763); new admissions contributed to the majority (61.68%) of TB cases, but prevalence was higher among inmates (1.75%) compared to new admissions (1.45%). Ukonga, an urban prison which incarcerates long-term convicted inmates had the highest prevalence of 4.02%. Male gender (OR=2.51, p<0.001), repeated incarcerations (OR=2.85, p<0.001), history of TB treatment (OR=1.78, p =0.002), TB symptoms (OR=2.78, p=0.006) and HIV infection (OR=2.86, p=0.002) were associated with positive TB results.ConclusionNew admissions could be the driving force of the TB epidemic in the penitentiary system. However, prison environments remain a major risk factor for developing active TB disease.
COVID-19 Symptoms and Immunotherapy in People with Multiple Sclerosis: An Analysis of the COVID-19 in MS Global Data Sharing Initiative Dataset
Authors: Garcia-Dominguez Maria A. , Srichawla Bahadar S. , Kipkorir Vincent 
Published: August 2023

ABSTRACTOBJECTIVESTo analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on immunotherapy using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset provided by PhysioNet.METHODSThe open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included body mass index (BMI), symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATAv1.5, R-Studiov1.1.447, Pythonv3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib.RESULTSA total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (p = 0.01), neuromuscular disorder (p = 0.046), hypertension (p = 0.005), chronic kidney disease (p < 0.001), and immunodeficiency (p = 0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization.CONCLUSIONThis study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease (CKD), and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.
Cystic fibrosis systemic immune profile is associated with lung microbes and characterized by widespread alterations in the innate and adaptive immune compartments
Authors: Rossi Elio , Lausen Mads , Friesgård Øbro Nina , Colque Antonella , Nielsen Bibi Uhre , Møller Rikke , de Gier Camilla , Hald Annemette , Skov Marianne , Pressler Tacjana , Molin Søren , Ostrowski Sisse Rye , Marquart Hanne Vibeke , Johansen Helle Krogh 
Published: August 2023

AbstractPolymicrobial airway infections and detrimental inflammation characterize patients with cystic fibrosis (CF), a disease with heterogeneous clinical outcomes. How the overall immune response is affected in CF, its relationships with the lung microbiome, and the source of clinical heterogeneity are unclear. Our work identifies a specific CF immune profile characterized by widespread hyperactivation, enrichment of CD35+/CD49d+neutrophils, and reduction in dendritic cells. Further, our data indicate signs of immune dysregulation due to alterations in Tregs homeostasis, which, together with an impaired B-cell immune function, are linked with patients’ lung function and are potentially the source of clinical heterogeneity. Indeed, clinical heterogeneity does not stem from a specific lung microbiome; yet, commensal bacteria correlate with higher concentrations of circulating immune cells and lower expression of leukocyte activation markers, a condition reversed by pathogenic microorganisms. Overall, our findings provide unique markers and immunomodulatory targets for improving the treatment of CF.
Antibodies Expand the Scope of Angiotensin Receptor Pharmacology
Authors: Skiba Meredith A. , Sterling Sarah M. , Rawson Shaun , Gilman Morgan S.A. , Xu Huixin , Nemeth Genevieve R. , Hurley Joseph D. , Shen Pengxiang , Staus Dean P. , Kim Jihee , McMahon Conor , Lehtinen Maria K. , Wingler Laura M. , Kruse Andrew C. 
Published: August 2023

AbstractG protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue, and cellular level. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays, and structural studies, we develop maternally selective heavy chain-only antibody (“nanobody”) antagonists against the angiotensin II type I receptor (AT1R) and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to AT1R with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich andevolvablepharmacology, attesting to their potential as next-generation GPCR modulators.
Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanisms
Authors: dos Santos Cristiane , Shrestha Shristi , Cottam Matthew , Perkins Guy , Lev-Ram Varda , Roy Birbickram , Acree Christopher , Kim Keun-Young , Deerinck Thomas , Cutler Melanie , Dean Danielle , Cartailler Jean Philippe , MacDonald Patrick E. , Hetzer Martin , Ellisman Mark , Arrojo e Drigo Rafael 
Published: August 2023

SummaryCaloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.