bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study
Authors: Alvikas Jurgis , Zenati Mazen , Campwala Insiyah , Jansen Jan O. , Hassoune Adnan , Phelos Heather , Okonkwo David O. , Neal Matthew D. 
Published: October 2021

BACKGROUND
Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients.

METHODS
We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later.

RESULTS
A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2–8] vs. 3.2 [interquartile range, 2–7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes.

CONCLUSION
Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH.

LEVEL OF EVIDENCE
Diagnostic tests, level II.
Leukemic and Lymphomatous Optic Neuropathy: A Case Series
Authors: Lee Victoria , Farooq Asim V. , Shah Hassan A. 
Published: October 2021

Background:
Optic neuropathy in the context of leukemia and lymphoma raises concern for central nervous system involvement or relapse and warrants prompt evaluation and treatment. To date, a gold standard for the diagnosis and management of leukemic optic neuropathy has yet to be established.

Methods:
Case series and review of the literature. Two illustrative cases were selected to discuss their treatment course and outcome.

Results:
We report 7 cases of patients with leukemia or lymphoma presenting with optic nerve infiltration. All patients received steroid therapy for presumed infiltrative optic neuropathy, and 4 patients underwent radiation therapy. Along with systemic chemotherapy, all patients received intrathecal chemotherapy except one. Three patients received chimeric antigen receptor T-cell therapy.

Conclusions:
Leukemic and lymphomatous optic neuropathy is difficult to diagnose and treat, and there is no gold standard for diagnosis or treatment in the current literature. We help clarify how this disease should be approached in a multidisciplinary fashion and on an individual basis to correctly diagnose and treat the vision loss, while considering the patient's long-term prognosis based on their systemic disease.
Factors Associated with the Risk of HIV Infection among HIV-exposed Infants in Malawi: 2013-2020
Authors: Ng’ambi Wingston , Estill Janne , Merzouki Fatma Aziza , Orel Erol , Chimpandule Tiwonge , Nyirenda Rose , Keiser Olivia 
Published: October 2021

AbstractBackgroundDespite the high availability of individual-level data of infants accessing HIV DNA polymerase chain reaction (DNA-PCR) testing service, there has been little in-depth analysis of such data. Therefore, we describe spatial and temporal trends in risk of HIV infection among Malawi’s HIV-exposed infants (HEI) with DNA-PCR HIV test result from 2013 to 2020.MethodsThis is an implementation study using routinely collected patient-level HIV DNA-PCR test result data extracted from the national Laboratory Management Information System database managed by the Department of HIV/AIDS between 1 January 2013 and 30 June 2020. We calculated frequencies, proportions and odds ratios (OR) with their associated 95% confidence intervals (95%CI). We performed a random-effects logistic regression to determine the risk factors associated with HIV infection in infants, controlling for the spatial autocorrelation between districts and adjusting for other variables.ResultsWe evaluated 255,229 HEI across 750 facilities in 28 districts. The overall risk of HIV infection among all tested HEI between 2013 and 2020 was 7.2% (95%CI: 7.1-7.3). We observed a decreasing trend in the proportion of HEI that tested HIV positive from 7.0% (95%CI: 6.6-7.4) in 2013 to 5.7% (95%CI: 5.4-5.9) in 2015 followed by an increase to 9.9% (95%CI: 9.6-10.2) in 2017 and then a decreasing trend to 4.2% (95%CI: 3.7-4.6) in 2020. The risk of HIV infection increased by age of the HEI. There was spatial heterogeneity of HIV prevalence between districts of Malawi.ConclusionWe summarised spatial and temporal trends of risk of HIV infection amongst HEI in Malawi between 2013 and 2020. There is need for further strengthening of EID program to ensure that all the HEI are enrolled in care by eight weeks of age in order to further reduce mother-to-child transmission of HIV.Key messageThere is need for further strengthening of the Malawi early infant diagnosis program to ensure that all the HIV-exposed infants are enrolled in care by eight weeks of age in order to eliminate mother-to-child transmission of HIV by 2030.What is known about the study?Malawi has implemented the Early Infant Diagnosis (EID) since 2009. Most of the studies on EID in Malawi have focused on just one or two health facilities.What the study adds?This is to our knowledge the first in-depth analysis of national routine data on HIV DNA-PCR tests among HIV-exposed infants with in Malawi. Our study has shown that there is spatial and temporal heterogeneity in risk of HIV infection amongst the HEI in Malawi between 2013 and 2020.
DIETARY MANIPULATION OF THE GUT MICROBIOME IN INFLAMMATORY BOWEL DISEASE PATIENTS: PROOF OF CONCEPT
Authors: Olendzki Barbara , Bucci Vanni , Cawley Caitlin , Maserati Rene , McManus Margaret , Olendzki Effie , Madziar Camilla , Chiang David , Ward Doyle V. , Pellish Randall , Foley Christine , Bhattarai Shakti , McCormick Beth A. , Maldonado-Contreras Ana 
Published: October 2021

ABSTRACTDiet is a modifiable, non-invasive, inexpensive behavior that is crucial in shaping the intestinal microbiome. A microbiome “imbalance” or dysbiosis in inflammatory bowel disease (IBD) is linked to inflammation. Here, we aim to define the impact of specific foods on bacterial species commonly depleted in patients with IBD to better inform dietary treatment. We performed a single-arm, pre-post intervention trial. After a baseline period, a dietary intervention with the IBD-Anti-Inflammatory Diet (IBD-AID) was initiated. We collected stool and blood samples and assessed dietary intake throughout the study. We applied advanced computational approaches to define and model complex interactions between the foods reported and the microbiome. A dense dataset comprising 553 dietary records and 340 stool samples was obtained from 22 participants. Consumption of prebiotics, probiotics, and beneficial foods correlated with increased abundance of Clostridia and Bacteroides, commonly depleted in IBD cohorts. We further show that the IBD-AID intervention affects the immune tone by lowering IL-8 and increasing GM-CSF with certain foods correlating with levels of those cytokines. By using robust predictive analytics, this study represents the first steps to detangle diet-microbiome interactions to inform personalized nutrition for patients suffering from dysbiosis-related IBD.
Improved morpho-syntax in discourse following intensive voice treatment in Parkinson’s disease: Secondary outcome variables from a Randomized Controlled Trial (RCT)
Authors: Ramage Amy E. , Greenslade Kathryn J. , Cote Kaila , Lee Jessica N. , Fox Cynthia M. , Halpern Angela , Ramig Lorraine O. 
Published: October 2021

AbstractIt is well established that voice is disordered in nearly 90% of individuals with Parkinson’s disease (PD). Given the role of voice in language expression, we pose that optimizing vocal function may lead to improved language production. Verb production is an area of language deficit in PD, particularly for verbs associated with an individual’s location of impairment (upper vs. lower limbs). It is thought that damage to the motor system, given its connection to action verbs, underlies this lexical effect. If this is the case, then treatment improving vocal motor function may also improve access to verbs. Nineteen participants with PD underwent Lee Silverman Voice Treatment (LSVT LOUD®), a 4-week intensive voice treatment (TXPD), in an IRB-approved randomized controlled voice treatment trial. Language production was contrasted with 20 untreated PD (UNTXPD) and 20 age-matched neurotypical control participants. Each provided 1-minute picture description narratives at baseline and after 4-weeks. Pre-post treatment within- and between-group comparisons identified effects of assessment time point and isolated treatment effects in the TXPD relative to UNTXPD and Controls. Given the intervention, the TXPD group demonstrated a significant increase in loudness during the picture description, as well as increased utterance length, diversity of word types used, verbs per utterance, and lexical density.
Evaluation of determinants of the serological response to the split-inactivated influenza vaccine
Authors: Wu Shaohuan , Ross Ted M. , Carlock Michael A. , Ghedin Elodie , Choi Hyungwon , Vogel Christine 
Published: October 2021

AbstractThe seasonal influenza vaccine is only effective in half of the vaccinated population. To identify determinants of vaccine efficacy, we used data from >1,300 vaccination events to predict the response to vaccination measured as seroconversion as well as hemagglutination inhibition (HAI) levels one year after. We evaluated the predictive capabilities of age, body mass index (BMI), sex, race, comorbidities, prevaccination history, and baseline HAI titers, as well as vaccination month and vaccine dose in multiple linear regression models. The models predicted the categorical response for >75% of the cases in all subsets with one exception. Prior vaccination, baseline titer level, and age were the strongest determinants on seroconversion, all of which had negative effects. Further, we identified a gender effect in older participants, and an effect of vaccination month. BMI played a surprisingly small role, likely due to its correlation with age. Comorbidities, vaccine dose, and race had negligible effects. Our models can generate a new seroconversion score that is corrected for the impact of these factors which can facilitate future biomarker identification.
Leveraging large multi-center cohorts of Alzheimer Disease endophenotypes to understand the role of Klotho heterozygosity on disease risk
Authors: Ali Muhammad , Sung Yun Ju , Wang Fengxian , Fernández Maria V. , Morris John C. , Fagan Anne M. , Blennow Kaj , Zetterberg Henrik , Heslegrave Amanda , Johansson Per M , Svensson Johan , Nellgård Bengt , Lleo Alberto , Alcolea Daniel , Clarimon Jordi , Rami Lorena , Molinuevo José Luis , Suárez-Calvet Marc , Morenas-Rodríguez Estrella , Kleinberger Gernot , Haass Christian , Ewers Michael ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Cruchaga Carlos 
Published: October 2021

AbstractTwo genetic variants (rs9536314 and rs9527025) in the Klotho gene, encoding a transmembrane protein, implicated on longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively healthy individuals that are APOE4 carriers. Specifically, the individuals heterozygous for this variant (KL-SVHET+), showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+has been suggested against amyloid burden for cognitively normal individuals. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we have performed a well-powered association analysis between KL-VSHET+and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+status with biomarkers for brain amyloidosis (e.g. CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72,P= 0.007) and tau pathology (e.g. biomarker negative for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94,P= 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68,P= 0.04) in elderly (60-80 years old) individuals that are cognitively normal and APOE4 carriers. Our work supports previous findings and suggests that the KL-VSHET+on a APOE4 genotype background may exert a protective effect by modulating the Aβ, Tau, and pTau burden and resulting cognitive decline in older controls susceptible to AD. The biological mechanism underlying APOE4 and KL-VSHET+interaction and the neuroprotective effect of KL-related pathways against amyloid accumulation may warrant future investigation as a target for preclinical pharmacological studies to explore novel AD drug targets.
DIRC3-IGFBP5 is a shared genetic risk locus and therapeutic target for carpal tunnel syndrome and trigger finger
Authors: Patel Benjamin , Kleeman Sam O. , Neavin Drew , Powell Joseph , Baskozos Georgios , Ng Michael , Ahmed Waheed-Ul-Rahman , Bennett David L. , Schmid Annina , Furniss Dominic , Wiberg Akira 
Published: October 2021

AbstractTrigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association study (GWAS) including 2,908 TF cases and 436,579 European controls in UKB, identifying five independent loci. Colocalization with CTS summary statistics identified a co-localized locus at DIRC3 (lncRNA), which was replicated in FinnGen and fine-mapped to rs62175241. Single-cell and bulk eQTL analysis in fibroblasts from healthy donors (n=79) and tenosynovium samples from CTS patients (n=77) showed that the disease-protective rs62175241 allele was associated with increased DIRC3 and IGFBP5 expression. IGFBP5 is a secreted antagonist of IGF-1 signaling, and elevated IGF-1 levels were associated with CTS and TF in UKB, thereby implicating IGF-1 as a driver of both diseases.
ATP-citrate lyase as a therapeutic target in chronic kidney disease: a Mendelian Randomization analysis
Authors: Mohammadi-Shemirani Pedrum , Chong Michael , Perrot Nicolas , Pigeyre Marie , Steinberg Gregory R. , Paré Guillaume , Krepinsky Joan C. , Lanktree Matthew B. 
Published: October 2021

AbstractBackgroundATP-citrate lyase (ACLY) inhibition is a promising therapeutic target for dyslipidemia, atherosclerotic cardiovascular disease, non-alcoholic steatohepatitis, and metabolic syndrome. Genetic analysis of its role in chronic kidney disease (CKD) has not been performed.MethodsWe constructed a genetic instrument by selecting variants associated with ACLY expression level in the expression quantitative trait loci genetics consortium (eQTLGen) that includes blood samples from 31,684 participants. In a two-sample Mendelian randomization analysis, we then evaluated the effect of genetically predicted ACLY expression on risk of CKD, estimated glomerular filtration rate (eGFR), and microalbuminuria using the CKD Genetics consortium (CKDGen), United Kingdom biobank, and the Finnish Genetics consortium (FinnGen) totaling 66,396 CKD cases and 958,517 controls.ResultsACLY is constitutively expressed in all cell types including in whole blood. The genetic instrument included 13 variants and explained 1.5% of variation in whole blood ACLY gene expression. A 34% reduction in genetically predicted ACLY expression was associated with a 0.04 mmol/L reduced low-density lipoprotein cholesterol (P = 3.4 × 10−4) and a 9% reduced risk of CKD (stage 3,4,5, dialysis or eGFR below 60 ml/min/1.73m2) (OR = 0.91, 95% C.I. 0.85-0.98, P = 0.008), but no association was observed with eGFR nor microalbuminuria.ConclusionMendelian Randomization analysis provides cautious optimism regarding the possibility of ACLY as a therapeutic target for CKD.
Monitoring and forecasting the COVID-19 epidemic in Moscow: model selection by balanced identification technology - version: September 2021
Authors: Sokolov Alexander , Sokolova Lyubov 
Published: October 2021

AbstractA mathematical model is a reflection of knowledge on the real object studied. The paper shows how the accumulation of data (statistical data and knowledge) about the COVID-19 pandemic lead to gradual refinement of mathematical models, to the expansion of the scope of their use. The resulting model satisfactorily describes the dynamics of COVID-19 in Moscow from 19.03.2020 to 01.09.2021 and can be used for forecasting with a horizon of several months. The dynamics of the model is mainly determined by herd immunity. Monitoring the situation in Moscow has not yet (as of 01.09.2021) revealed noticeable seasonality of the disease nor an increase in infectivity (due to the Delta strain). The results of using balanced identification technology to monitor the COVID-19 pandemic are:models corresponding to the data available at different points in time (from March 2020 to August 2021);new knowledge (dependencies) acquired;forecasts for the third and fourth waves in Moscow.Discrepancies that manifested after 01.09.2021 and possible further modifications of the model are discussed
TNFα SIGNALLING IN THE CUTANEOUS IMMUNE NETWORK INSTRUCTS LOCAL Th17 ALLERGEN-SPECIFIC INFLAMMATORY RESPONSES IN ATOPIC DERMATITIS
Authors: Sirvent Sofia , Vallejo Andres , Corden Emma , Teo Ying , Davies James , Clayton Kalum , Seaby Eleanor , Lai Chester , Ennis Sarah , Alyami Rfeef , Dean Lareb , Loxham Matthew , Horswill Sarah , Healy Eugene , Roberts Graham , Hall Nigel J. , Bennett Clare L. , Friedmann Peter , Singh Harinder , Ardern-Jones Michael , Polak Marta E 
Published: October 2021

AbstractAccurate regulation of cutaneous immunity is fundamental for human health and quality of life but is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance vs inflammation in human skin, we set up a human in vivo allergen challenge study, exposing patients with atopic dermatitis (AD) to house dust mite (HDM). Analyses of transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of resident and infiltrating immune cells indicated that inflammatory responses to HDM were associated with immune activation in Langerhans cells (LCs) and cutaneous T cells. High basal level of TNFα production by cutaneous Th17 T cells predisposed to an inflammatory reaction and resulted in formation of hub structures where LCs and T cells interacted, leading to loss of functional programming in LCs. Additionally, single nucleotide polymorphisms in MT1X gene associated with enhanced expression of metallothioneins and transcriptional programmes encoding antioxidant defences across skin cell types in non-reactive patients, were protective against T cell mediated inflammation. Our results provide a unique insight into the dynamics of immune regulation in the human skin and define regulatory circuits that can be harnessed to improve skin health and treat disease.
Linking Profiles of Pathway Activation with Clinical Motor Improvements – a Retrospective Computational Study
Authors: Butenko Konstantin , Li Ningfei , Neudorfer Clemens , Roediger Jan , Horn Andreas , Wenzel Gregor R. , Eldebakey Hazem , Kühn Andrea A. , Reich Martin , Volkmann Jens , van Rienen Ursula 
Published: October 2021

AbstractDeep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease.In silicocomputer models for DBS allow to pre-select a set of potentially optimal stimulation parameters. If efficacious, they could further carry insight into the mechanism of action of DBS and foster the development of more efficient stimulation approaches. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulation of neural activity. We use the concept of pathway activation modeling, which incorporates advanced volume conductor models and anatomically authentic fiber trajectories to estimate DBS-induced action potential initiation in anatomically plausible pathways that traverse in close proximity to targeted nuclei. We apply the method on a retrospective dataset with the aim of providing a model-based prediction of clinical improvement following DBS (as measured by the motor part of the Unified Parkinson’s Disease Rating Scale). Based on differences in outcome and activation rates for two DBS protocols in a training cohort, we compute a theoretical 100% improvement profile and enhance it by analyzing the importance of profile matching for individual pathways. Finally, we validate the performance of our profile-based predictive model in a test cohort. As a result, we demonstrate the clinical utility of pathway activation modeling in the context of motor symptom alleviation in Parkinson’s patients treated with DBS.