bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality from Sickle Cell Disease in Brazil
Authors: Blatyta PF , DiLorenzo C , Gomes I , Salomon T , Sabino EC , Capuani L , Cruz DTS , Maximo C , Flor-Park MV , Mota RA , Werneck Rodrigues DO , Dinardo CL , Almeida-Neto C , Custer B , Kelly S ,   Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) International Component Brazil
Published: June 2023

AbstractIntroductionMany individuals with sickle cell disease (SCD) die before age 60, despite early detection via neonatal screening and implementation of treatments such as vaccines and antibiotic prophylaxis and the increasing availability of disease modifying therapies. This study evaluated the causes and independent predictors of mortality in a SCD population in Brazil.MethodsThis analysis was performed within the multicenter Recipient Epidemiology and Donor Evaluation (REDS)-III SCD cohort which was established at 6 participating centers in Brazil from 2013-2018. Participants were randomly selected as eligible and recruited at routine visits. Medical records were reviewed to abstract clinical and laboratory data. Mortality and cause of death were confirmed by local chart review as well as linkage to the Brazilian death certificate database. Key variables were compared between deceased and alive participants using Chi2test for categorical variables and Mann-Whitney test for continuous variables. Stepwise logistic regression then a Cox regression multivariable model was performed to identify independent predictors for mortality within the adult participants.ResultsThere were 2,793 participants in the cohort (1,558, 55.8%, <18 years) and 159 (5.7%) were confirmed to be deceased by the end of follow up: 142 adults (>18 years) and 17 children. The median life expectancy was 65.7. Within adults, infection was the main identifiable cause of death (33.3%), followed by pulmonary causes (25.2%) and neurologic causes (14.5%). Five (3.1%) patients had an unknown cause of death. Independent predictors of mortality were age [Hazard Ratio (HR) 1.03; 95% CI 1.01-1.04; p<.01], iron overload (HR 1.68; 95% CI1.09-2.60; p<.02] and previous hospital admission (HR 1.68; 95% CI 1.10-2.56; p<.02).DiscussionMortality in Brazilian SCD individuals is shifting from children to adults, with increased rates of death in the third and fourth decades of life. Individuals with SCD are dying 10 years before the general population in Brazil. The main causes of death in our cohort were infections, acute chest syndrome and stroke, highlighting the need for prompt recognition and treatment of these complications. Screening and treatment for iron overload and closer monitoring and consideration of disease modifying therapies for patients with frequent hospital admissions are important as both were identified as independent predictors of mortality.
Comparing the effect profile of CETP in individuals of East Asian and European ancestries
Authors: Dunca Diana , Chopade Sandesh , Gordillo-Marañón María , Hingorani Aroon D. , Kuchenbaecker Karoline , Finan Chris , Schmidt Amand F. 
Published: June 2023

AbstractBackgroundCholesteryl ester transfer protein (CETP) is a lipid drug target under development for coronary heart disease (CHD) in both European and East Asian populations. Previous drug target Mendelian randomization (MR) studies conducted in East Asians failed to show a CHD effect, which has been interpreted as lack of effectiveness of CETP inhibition for CHD prevention in this population.ObjectivesIn this study, we inferred the effect of CETP inhibition in individuals of European and East Asian ancestries using drug target Mendelian randomization.MethodsWe leveraged genetic associations ofCETPvariants with major blood lipid fractions for individuals of European (n=1,320,016) and East Asian (n=146,492) ancestries. Colocalization was employed to identify potential cross-ancestry signals ofCETPvariants for plasma concentrations of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C). Drug target MR was used to estimate ancestry-specific effects of on-targetCETPinhibition. Differences between ancestries were evaluated using interaction tests, applying a multiplicity corrected alpha of 1.9×10-3based on the 26 considered traits.ResultsThere was strong support (posterior probability: 1.00) of a shared causalCETPvariant affecting HDL-C in both populations, which was not observed for LDL-C. Employing drug target MR scaled to a standard deviation increase in HDL-C, we found that lower CETP was associated with lower LDL-C, Lp[a], systolic blood pressure and pulse pressure in both groups, but the effects were more pronounced in European individuals (interaction p-values < 1.9×10-3). Lower CETP was protective against CHD, angina, intracerebral haemorrhage and heart failure in both ancestries, for example for CHD in East Asians (OR 0.89, 95%CI 0.84;0.94) compared to Europeans (OR 0.95, 95%CI 0.92;0.99, interaction p-value=0.05).ConclusionsIn conclusion, on-target inhibition of CETP is anticipated to decrease cardiovascular disease in individuals of both European and East Asian ancestries.
Exploring [11C]CPPC as a CSF1R-targeted PET Imaging Marker for Early Parkinson’s Disease Severity
Authors: Mills Kelly A. , Du Yong , Coughlin Jennifer M. , Foss Catherine A. , Horti Andrew G. , Jenkins Katelyn , Skorobogatova Yana , Spiro Ergi , Motley Chelsie S. , Dannals Robert F. , Song Jae-Jin , Choi Yu Ree , Redding-Ochoa Javier , Troncoso Juan , Dawson Valina L. , Kam Tae-In , Pomper Martin G. , Dawson Ted M. 
Published: June 2023

AbstractNeuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson’s disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system’s innate immune response. Using immunologic methods, we show that CSF1R in human brain is colocalized with the microglial marker, ionized calcium binding adaptor molecule 1 (Iba1). In PD, CSF1R immunoreactivity is significantly increased in PD across multiple brain regions, with the largest differences in the midbrain versus controls. Autoradiography revealed significantly increased [3H]JHU11761 binding in the inferior parietal cortex of PD patients. PET imaging demonstrated that higher [11C]CPPC binding in the striatum was associated with greater motor disability in PD. Furthermore, increased [11C]CPPC binding in various regions correlated with more severe motor disability and poorer verbal fluency. This study finds that CSF1R expression is elevated in PD and that [11C]CPPC-PET imaging of CSF1R is indicative of motor and cognitive impairments in the early stages of the disease. Moreover, the study underscores the significance of CSF1R as a promising biomarker for neuroinflammation in Parkinson’s disease, suggesting its potential use for non-invasive assessment of disease progression and severity, leading to earlier diagnosis and targeted interventions.Significance StatementThis study demonstrates that the Colony Stimulating Factor 1 Receptor (CSF1R) colocalizes with microglial markers in the human brain, and the research establishes elevated CSF1R expression in PD autopsy tissues. Employing [11C]CPPC-PET imaging, the study unveils a correlation between increased CSF1R binding and both motor disability and cognitive decline in PD patients. These findings highlight the potential of CSF1R as a novel biomarker for neuroinflammation in PD, offering a non-invasive means to assess disease progression and severity, ultimately contributing to earlier diagnosis and targeted interventions.
Genetic and non-genetic components of family history of stroke and heart disease: a population-based study among adopted and non-adopted individuals
Authors: Mayerhofer Ernst , Parodi Livia , Narasimhalu Kaavya , Harloff Andreas , Georgakis Marios K , Rosand Jonathan , Anderson Christopher D 
Published: June 2023

AbstractBackgroundIt is increasingly clear that genetic and non-genetic factors account for the association of family history with disease risk in offspring. We sought to distinguish the genetic and non-genetic contributions of family history of stroke and heart disease on incident events by examining adopted and non-adopted individuals.MethodsWe examined associations between family history of stroke and heart disease with incident stroke and myocardial infarction (MI) in 495,640 participants of the UK Biobank (mean age 56.5 years, 55% female) stratified by early childhood adoption status into adoptees (n=5,747) and non-adoptees (n=489,893). We estimated hazard ratios (HRs) per affected nuclear family member, and for polygenic risk scores (PRS) for stroke and MI in Cox models adjusted for baseline age and sex.Results12,518 strokes and 23,923 MIs occurred over a 13-year follow-up. In non-adoptees, family history of stroke and heart disease were associated with increased stroke and MI risk, with the strongest association of family history of stroke for incident stroke (HR 1.16 [1.12, 1.19]) and family history of heart disease for incident MI (HR 1.48 [1.45, 1.50]). In adoptees, family history of stroke associated with incident stroke (HR 1.41 [1.06, 1.86]), but family history of heart disease did not associate with incident MI (p>0.5). PRS showed strong disease-specific associations in adoptees and non-adoptees. In non-adoptees, the stroke PRS mediated 6% risk between family history of stroke and incident stroke, and the MI PRS mediated 13% risk between family history of heart disease and MI.ConclusionsFamily history of stroke and heart disease increase risk for their respective conditions. Family history of stroke contains a substantial proportion of potentially modifiable non-genetic risk, indicating a need for further research to elucidate these elements for novel prevention strategies, whereas family history of heart disease represents predominantly genetic risk.Graphic abstract
Patterns of long-term care utilization during the last five years of life among Swedish older adults with and without dementia
Authors: sm-Rahman Atiqur , Meinow Bettina , Hydén Lars-Christer , Kelfve Susanne 
Published: June 2023

AbstractAimsThe aims of this study were to compare the patterns of long-term care (LTC) use (no care, homecare, residential care) among people with and without dementia aged 70+ in Sweden during their last five years of life and its association with sociodemographic factors and time with a dementia diagnosis.MethodsThis retrospective cohort study included all people who died in November 2019 aged 70 years and older (n=6294) derived from several national registers. A multinomial logistic regression was conducted to identify which sociodemographic factors predicted the patterns of LTC use and predicted proportions were calculated from the margins command.ResultsResults showed that the time with a dementia diagnosis and cohabitation status were important predictors that influence the patterns of LTC use during the last five years of life. Nearly three-quarters of people living with dementia (PlwD) used residential care during the last five years of life. PlwD were more likely to reside in residential care close to death. Women who lived alone, with or without dementia, used residential care to a higher degree compared to married or cohabiting women.ConclusionsAmong people without a dementia diagnosis, as well as those who were newly diagnosed, it was common to have no LTC at all, or use LTC only for a brief period close to death. During the last five years of life, PlwD who were living alone more often entered LTC early and used residential care for a longer time compared to those without dementia.
The fungal intestinal microbiota predict the development of bronchopulmonary dysplasia in very low birthweight newborns
Authors: Willis Kent A. , Silverberg Mary , Martin Isaac , Abdelgawad Ahmed , Tanaka Kosuke , Karabayir Ibrahim , Halloran Brian A. , Myers Erin D. , Desai Jay P. , White Catrina T. , Lal Charitharth V. , Ambalavanan Namasivayam , Peters Brian M. , Jain Viral G. , Akbilgic Oguz , Tipton Laura , Jilling Tamás , Cormier Stephania A. , Pierre Joseph F. , Talati Ajay J. 
Published: June 2023

AbstractRationaleBronchopulmonary dysplasia (BPD) is the most common morbidity affecting very preterm infants. Gut fungal and bacterial microbial communities contribute to multiple lung diseases and may influence BPD pathogenesis.MethodsWe performed a prospective, observational cohort study comparing the multikingdom fecal microbiota of 144 preterm infants with or without moderate to severe BPD by sequencing the bacterial 16S and fungal ITS2 ribosomal RNA gene. To address the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model. Comparisons were made using RNA sequencing, confocal microscopy, lung morphometry, and oscillometry.ResultsWe analyzed 102 fecal microbiome samples collected during the second week of life. Infants who later developed BPD showed an obvious fungal dysbiosis as compared to infants without BPD (NoBPD,p= 0.0398, permutational multivariate ANOVA). Instead of fungal communities dominated byCandidaandSaccharomyces, the microbiota of infants who developed BPD were characterized by a greater diversity of rarer fungi in less interconnected community architectures. On successful colonization, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals. We identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury.ConclusionsThe gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.Conclusions: The gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.
Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression
Authors: Wall Matthew B. , Demetriou Lysia , Giribaldi Bruna , Roseman Leor , Ertl Natalie , Erritzoe David , Nutt David J. , Carhart-Harris Robin L. 
Published: June 2023

AbstractPsilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two groups with major depressive disorder: 1) a ‘psilocybin group’ that received two dosing sessions with 25mg plus six weeks of daily placebo, and 2) an ‘escitalopram group’ that received six weeks of the SSRI escitalopram, plus two dosing sessions with an inactive/placebo dose of 1mg psilocybin. Both groups had an equal amount of psychological support throughout. An emotional face fMRI paradigm was completed at baseline (pre-treatment) and at the six-week post-treatment primary endpoint (three weeks following psilocybin dosing sessions). An analysis examining the interaction between patient group (psilocybin vs. escitalopram) and time-point (pre-vs. post-treatment) showed a robust effect in a distributed network of cortical brain regions. Follow-up analyses showed that post-treatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change, or even a slight increase, in the psilocybin group. Specific analyses of the amygdala showed a reduction of response to fear faces in the escitalopram group, but no effects for the psilocybin group. Despite large improvements in depressive symptoms in the psilocybin group, psilocybin-therapy had only a minor effect on brain responsiveness to emotional stimuli. We suggest that reduced emotional responsiveness may be a biomarker of SSRIs’ antidepressant action that is not shared by psilocybin-therapy.
Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer’s disease
Authors: Rodríguez-Fernández Blanca , Sánchez-Benavides Gonzalo , Genius Patricia , Minguillon Carolina , Fauria Karine , Vivo Immaculata De , Navarro Arcadi , Molinuevo Jose Luis , Gispert Juan D. , Sala-Vila Aleix , Vilor-Tejedor Natalia , Crous-Bou Marta ,   the ALFA study
Published: June 2023

AbstractINTRODUCTIONLeukocyte telomere length (LTL) is an objective biomarker of biological aging, and it is proposed to play a crucial role in Alzheimer’s disease (AD) risk. We aimed at evaluating the cross-sectional association between LTL and cognitive performance in middle-aged cognitively unimpaired individuals at increased risk of AD.METHODSA total of 1,520 participants from the ALFA cohort were included. Relative telomere length was measured in leukocytes through qPCR. LTL was residualized against age and sex, and associations with cognitive performance were assessed in accelerated and decelerated biological aging individuals based on residual LTL (rLTL). Interactions with sex and genetic risk of AD were tested.RESULTSNon-linear associations were found between LTL and episodic memory (EM). Better EM was associated with longer rLTL among women in the accelerated aging group.DISCUSSIONResults suggest a potential role for telomeres in maintaining cognition in aging with sex-specific patterns.Highlights:● There is a non-linear association between telomere length and cognitive performance.● Longer telomeres are suggested to have a beneficial effect on episodic memory.● The association between telomeres and cognitive performance might be sex-specific.
Differences in Cardiac Mechanics among Genetically At-Risk First-Degree Relatives: The DCM Precision Medicine Study
Authors: Wilcox Jane E. , Beussink-Nelson Lauren , Cao Jinwen , Kumar Ritika , Jordan Elizabeth , Ni Hanyu , Shah Sanjiv J. , Hershberger Ray E. , Kinnamon Daniel D. 
Published: June 2023

ABSTRACTAimsAmong genetically at-risk first-degree relatives (FDRs) of probands with dilated cardiomyopathy (DCM), the ability to detect changes in left ventricular (LV) mechanics with normal LV size and ejection fraction (LVEF) remains incompletely explored. We sought to define a pre-DCM phenotype among at-risk FDRs, including those with variants of uncertain significance (VUSs), using echocardiographic measures of cardiac mechanics.Methods and ResultsLV structure and function, including speckle-tracking analysis for LV global longitudinal strain (GLS), were evaluated in 124 FDRs (65% female; median age 44.9 [IQR: 30.6-60.3] years) of 66 DCM probands of European ancestry sequenced for rare variants in 35 DCM genes. FDRs had normal LV size and LVEF. Negative FDRs of probands with pathogenic or likely pathogenic (P/LP) variants (n=28) were a reference group to which negative FDRs of probands without P/LP variants (n=30), FDRs with only VUSs (n=27), and FDRs with P/LP variants (n=39) were compared. In an analysis accounting for age-dependent penetrance, FDRs below the median age showed minimal differences in LV GLS across groups while those above it with P/LP variants or VUSs had lower absolute values than the reference group (−3.9 [95% CI: −5.7, −2.1] or −3.1 [−4.8, −1.4] %-units) and negative FDRs of probands without P/LP variants (−2.6 [−4.0, −1.2] or −1.8 [−3.1, −0.6]).ConclusionsOlder FDRs with normal LV size and LVEF who harbored P/LP variants or VUSs had lower absolute LV GLS values, indicating that some DCM-related VUSs are clinically relevant. LV GLS may have utility for defining a pre-DCM phenotype.Clinical Trial Registrationclinicaltrials.gov,NCT03037632Graphical AbstractDifferences in Cardiac Mechanics among Genetically At-Risk First-Degree Relatives: The DCM Precision Medicine Study.DCM = dilated cardiomyopathy, FDR = first-degree relative, GLS = global longitudinal strain, HF = heart failure, LP = likely pathogenic, LV = left ventricular, LVEF = left ventricular ejection fraction, P = pathogenic, VUS = variant of uncertain significance.
Economic Evaluation of State Control, Low Price, and Research-Based Policy for Eating Disorders Treatment in Sweden
Authors: Södersten Per , Brodin Ulf , Bergh Cecilia 
Published: June 2023

AbstractIntroductionPorter and Olmsted Teisberg suggested that the value of healthcare should be measured by treatment outcomes related to costs. Policy should financially reward treatment effects and in an outline of value-based healthcare, they predicted:State control policy yields variable effects, increasing costsLow price policy decreases effects, increasing costsResearch and Development (R&D) policy increases effects, decreasing costsMethodsThe treatment of eating disorders in Region Stockholm, Sweden, in years 2012-2016 makes it possible to test these predictions because a State control, a Low price, and an R&D provider were contracted and the effects and costs of their treatments are publically available from Region Stockholm.ResultsThe State control provider was contracted to provide more care services than the other providers. The average yearly number of patients treated to remission/patients treated was 164/714 (23%) at the State control provider, 41/170 (24) at the Low price provider, and 152/192 (79%) at the R&D provider. The average yearly budget was 73 million Swedish crowns (MSEK) compared to 49 MSEK at the R&D provider and 32 MSEK at the Low price provider (on average 30% lower per care service than the two other providers). The average cost to treat a patient to remission/patients treated was highest at the Low price provider (859 KSEK), followed by the State control provider (464 KSEK) and the R&D provider (327 KSEK).ConclusionsThe results confirm Porter and Olmsted Teisberg’s three predictions and suggest that an R&D policy increases the value of healthcare.
The Neurocognome in Childhood: Relevance of Neurocognitive Network Organization
Authors: Königs M. , Kooper C.C. , Oosterlaan J. 
Published: June 2023

AbstractNeurocognitive functioning is crucial for child development, but the relevance of interplay between neurocognitive functions in childhood remains poorly understood. This explores the relevance of neurocognitive network organization in childhood by the application of network theory to neurocognitive data at the individual level. A community sample of children (N = 132), between 6 and 18 years of age (M = 11.4) performed computerized neurocognitive testing. Neurocognitive connectivity was calculated between each pair of test scores, creating individual connectivity matrices after which graph theory was applied to determine global network organization and local network organization. The relation between demographics and neurocognitive network organization was investigated with correlation analysis. The relevance for intelligence (Wechsler short forms) and behavioral problems (Strength and Difficulties Questionnaire) was assessed with multivariate regression. K-means clustering was applied to investigate the correspondence between typical neurocognitive network organizations and conventionally assessed neurocognitive performance. The results show that global as well as local neurocognitive network organization is related to age, intelligence and behavior problems. Moreover, children from neurocognitive clusters with typical configurations of global network organization also differed in terms of conventionally assessed neurocognitive performance. In conclusion, this study provides cross-sectional evidence suggesting the presence of developmental reorganization of the interplay between neurocognitive functions. Neurocognitive network organization is also related to crucial aspects of functioning in children (intelligence, behavior problems) and the level of conventionally assed neurocognitive performance. Thereby, this study shows that individual network analysis provides a complementary view on the child functioning and may hold relevance for a better understanding of child development and the influence of neuropathology on daily life functioning.