Oral anticoagulant therapy at hospital admission associates with lower mortality in older COVID-19 patients with atrial fibrillation. An insight from the Covid Registry

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. ONBEHALF: the GeroCovid Investigators Introduction. Atrial fibrillation (AF), the arrhythmia most frequently diagnosed in older patients, associates with serious, thrombo-embolic, complications and high mortality. COVID-19 severely affects aged subjects, determining an important prothrombotic status. Purpose. Aim of this study was to evaluate mortality-related factors in older AF patients with COVID-19.  Methods. We included 806 in-hospital COVID-19 patients aged 60 years or more hospitalized between March 1st and June 6th 2020 and enrolled in a multicenter observational study. Results. The prevalence of AF was 21.8%. In-hospital mortality was higher in the AF group (36.9 vs. 27.5%; p = 0.015). Among AF patients, those who survived were younger (81 ± 8 vs. 84 ± 7 years; p = 0.002), had a lower CHA2DS2-VASc score (3.9 ± 1.6 vs. 4.4 ± 1.3; p = 0.02) and were more frequently treated with oral anticoagulants at admission (63.1 vs. 32.3%; p < 0.001) than those who died in hospital. At multivariable logistic regression analysis, lower age (p = 0.042), a better functional profile (p = 0.007), less severe COVID-19 manifestations at admission (p = 0.001), and the use of Vitamin K antagonists (OR = 0.16, 95%CI: 0.03-0.84; p = 0.031) or DOACs (OR = 0.22, 95%CI: 0.08-0.56; p = 0.002), compared to antiplatelet therapy or no treatment at all, were associated with a lower chance of in-hospital death. Conclusions. AF is a prevalent condition and a severity factor in older COVID-19 patients. Advanced age, dependency and severe clinical manifestations of disease characterized older AF subjects with a worse prognosis. Interestingly, pre-admission anticoagulant therapy correlated positively with in-hospital survival

The Impact of the COVID-19 Pandemic on the Psychological Well-Being of Caregivers of People with Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

The aim of this systematic review was to investigate the effects of the COVID-19 lockdown on the psychological well-being of caregivers of people with dementia or mild cognitive impairment (PwD/MCI). Electronic databases were searched from inception to August 2022 for observational studies investigating the COVID-19 lockdown and psychological well-being of caregivers of PwD/MCI. Summary estimates of standardized mean differences (SMD) in psychological well-being scores pre- versus during COVID-19 were calculated using a random-effects model. Fifteen studies including 1702 caregivers (65.7% female, mean age 60.40 ± 12.9 years) with PwD/MCI were evaluated. Five studies found no change in psychological well-being parameters, including depression, anxiety, distress, caregiver burden, and quality of life. Ten studies found a worsening in at least one parameter: depression (six studies, n = 1368; SMD = 0.40; 95%CI: 0.09–0.71; p = 0.01, I2 = 86.8%), anxiety (seven studies, n = 1569; SMD = 1.35; 95%CI: 0.05–2.65; I2 = 99.2%), caregiver distress (six studies, n = 1320, SMD = 3.190; 95%CI: 1.42–4.95; p &lt; 0.0001; I2 = 99.4%), and caregiver burden (four studies, n = 852, SMD = 0.34; 95%CI: 0.13–0.56; p = 0.001; I2 = 54.1%) (p &lt; 0.05). There was an increase in depression, anxiety, caregiver burden, and distress in caregivers of PwD/MCI during the lockdown in the COVID pandemic. This could have longer term consequences, and it is essential that caregivers’ psychological well-being is assessed and supported, to benefit both themselves and those for whom they care

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Psychological Well-Being of Older Adults With Cognitive Deterioration During Quarantine: Preliminary Results From the GeroCovid Initiative

Objectives: The spread of COVID-19 has undeniably unsettled the social, psychological and emotional life of the entire world population. Particular attention should be paid to older adults with dementia, given their vulnerability to emotional stressors. The aim of this retrospective study is to evaluate the impact of the first wave quarantine related to Covid-19 on psychological and affective well-being of older adults with mild/major neurocognitive disorders and of their caregivers.Methods: Data on participants' assessment before the quarantine (PREQ) were retrospectively collected. Patients with Mild Cognitive Impairment (MCI) or dementia were recruited from different Centers for Cognitive Decline and Dementia in Italy. During the quarantine, psychological and affective well-being were evaluated by phone through the administrations of scales measuring anxiety and depression (DASS), perceived stress (PSS), coping strategies (COPE) and the caregivers' burden (CBI). The scales' results were compared across participants' PREQ cognitive level (Mini Mental State Examination, MMSE ≥25, 23–24, and ≤ 22) with multiple linear regression models.Results: The sample included 168 patients (64% women) with a mean age of 79 ± 7 years. After adjusting for potential confounders, more severe cognitive impairment was independently associated with higher DASS and PSS score, and poorer coping strategies (p &lt; 0.05). Cognitive functioning was also inversely associated with CBI.Conclusions: The impact of the quarantine on the psycho-affective well-being of individuals with MCI and dementia and on caregivers' burden varies according to the PREQ cognitive functioning with more severely impaired patients having worse outcomes

Genotype-free demultiplexing of pooled single-cell RNA-seq

A variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We introduce scSplit which utilizes genetic differences inferred from scRNA-seq data alone to demultiplex pooled samples. scSplit also enables mapping clusters to original samples. Using simulated, merged, and pooled multi-individual datasets, we show that scSplit prediction is highly concordant with demuxlet predictions and is highly consistent with the known truth in cell-hashing dataset. scSplit is ideally suited to samples without external genotype information and is available at: https://github.com/jon-xu/scSplit

Spectroscopic Confirmation of a Population of Isolated, Intermediate-Mass YSOs

Wide-field searches for young stellar objects (YSOs) can place useful constraints on the prevalence of clustered versus distributed star formation. The Spitzer/IRAC Candidate YSO (SPICY) catalog is one of the largest compilations of such objects (~120,000 candidates in the Galactic midplane). Many SPICY candidates are spatially clustered, but, perhaps surprisingly, approximately half the candidates appear spatially distributed. To better characterize this unexpected population and confirm its nature, we obtained Palomar/DBSP spectroscopy for 26 of the optically-bright (G<15 mag) "isolated" YSO candidates. We confirm the YSO classifications of all 26 sources based on their positions on the Hertzsprung-Russell diagram, H and Ca II line-emission from over half the sample, and robust detection of infrared excesses. This implies a contamination rate of <10% for SPICY stars that meet our optical selection criteria. Spectral types range from B4 to K3, with A-type stars most common. Spectral energy distributions, diffuse interstellar bands, and Galactic extinction maps indicate moderate to high extinction. Stellar masses range from ~1 to 7 $M_\odot$, and the estimated accretion rates, ranging from $3\times10^{-8}$ to $3\times10^{-7}$ $M_\odot$ yr$^{-1}$, are typical for YSOs in this mass range. The 3D spatial distribution of these stars, based on Gaia astrometry, reveals that the "isolated" YSOs are not evenly distributed in the Solar neighborhood but are concentrated in kpc-scale dusty Galactic structures that also contain the majority of the SPICY YSO clusters. Thus, the processes that produce large Galactic star-forming structures may yield nearly as many distributed as clustered YSOs.Comment: Accepted for publication in AJ. 22 pages, 9 figures, and 4 tables. Figure sets are available from https://sites.astro.caltech.edu/~mkuhn/SPICY/PaperIII

Diagnosis of Kawasaki disease using a minimal whole blood gene expression signature

Importance There is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms. Objective To identify a whole blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions. Design Case-control discovery study groups comprising training, test, and validation groups of children with KD or comparator febrile illness. Setting Hospitals in the UK, Spain, Netherlands and USA. Participants The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, 242 bacterial or viral infections) and 55 healthy controls. The independent validation group included 130 febrile children and 102 KD patients, including 72 in the first 7 days of illness. Exposures Whole blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (Parallel Deterministic Model Search). Main outcomes and measures The ability of transcript signatures - implemented as Disease Risk Scores - to discriminate KD cases from controls, was assessed by Area Under the Curve (AUC), sensitivity, and specificity at the optimal cut-point according to Youden’s index. Results A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set with AUC, sensitivity, and specificity (95% confidence intervals (CI)) of 96.2% (92.5-99.9), 81.7% (60.0-94.8), and 92.1% (84.0-97.0), respectively. In the validation set, the signature distinguished KD from febrile controls with AUC, sensitivity, and specificity (95% CI) of 94.6% (91.3-98.0), 85.9% (76.8-92.6), and 89.1% (83.0-93.7) respectively. The signature was applied to clinically defined categories of Definite, Highly Probable and Possible KD resulting in AUCs of 98.1%, 96.3% and 70.0% respectively, mirroring clinical certainty. Conclusions and relevance A 13-transcript blood gene expression signature distinguished KD from other febrile conditions. Diagnostic accuracy increased with certainty of clinical diagnosis. A test incorporating the 13-transcript Disease Risk Score may enable earlier diagnosis and treatment of KD, and reduce inappropriate treatment in those with other diagnoses

Dissociation of CAK from Core TFIIH Reveals a Functional Link between XP-G/CS and the TFIIH Disassembly State

Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation

Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this recordSplit-hand/foot malformation type 1 is an autosomal dominant condition with reduced penetrance and variable expression. We report three individuals from two families with split-hand/split-foot malformation (SHFM) in whom next generation sequencing was performed to investigate the cause of their phenotype.Wellcome Trus