Miracle-dz/UniFAR-FTUs huggingface dataset:
Coronavirus Surveillance in a Pediatric Population in Jordan From 2010 to 2013

Background: Human coronaviruses (HCoVs) are a significant cause of acute respiratory illness (ARI) in children; however, the role of HCoVs in ARI among hospitalized children in the Middle East is not well defined. Methods: Children under 2 years admitted with fever and/or respiratory symptoms were enrolled from 2010 to 2013 in Amman, Jordan. Nasal/throat swabs were collected and stored for testing. Demographic and clinical characteristics were collected through parent/guardian interviews and medical chart abstractions. Prior stored specimens were tested for HCoVs (HKU1, OC43, 229E and NL63) by qRT-PCR. Results: Of the 3168 children enrolled, 6.7% were HCoVs-positive. Among HCoV-positive children, the median age was 3.8 (1.9–8.4) months, 59% were male, 14% were premature, 11% had underlying medical conditions and 76% had viral-codetection. The most common presenting symptoms were cough, fever, wheezing and shortness of breath. HCoVs were detected year-round, peaking in winter-spring months. Overall, 56%, 22%, 13% and 6% were OC43, NL63, HKU1 and 229E, respectively. There was no difference in disease severity between the species, except higher intensive care unit admission frequency in NL63-positive subjects. Conclusions: HCoVs were detected in around 7% of children enrolled in our study. Despite HCoV detection in children with ARI with highest peaks in respiratory seasons, the actual burden and pathogenic role of HCoVs in ARI merits further evaluation given the high frequency of viral codetection.
Childhood Abuse and Cognitive Function in a Large Cohort of Middle-Aged Women

Cognitive function at middle age is of particular public health interest, as it strongly predicts later dementia. Children who have experienced abuse subsequently have worse cognitive function than those who have not. However, it remains unclear whether the association of abuse with cognitive function persists into middle age. In 2014–2016, 14,151 women ages 49–69 years who had previously responded to a childhood abuse questionnaire completed a cognitive battery. In models adjusted for childhood socioeconomic status and head trauma, combined physical, emotional, and sexual abuse was associated with lower scores on both Learning/Working Memory (severe abuse, lower scores similar to that observed in women 4.8 years older in our data) and Psychomotor Speed/Attention (severe abuse, lower scores similar to that observed in women to 2.9 years older in our data). Adjustment for adulthood socioeconomic status and health factors (e.g., smoking, hypertension) slightly attenuated associations. In exploratory analyses further adjusted for psychological distress, associations were attenuated. Women exposed versus unexposed to childhood abuse had poorer cognitive function at mid-life. Associations were particularly strong for learning and working memory and were not accounted for by adulthood health factors. Childhood abuse should be investigated as a potential risk factor for cognitive decline and dementia in old age.
Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R 2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R 2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R 2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R 2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = . 029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.
High-throughput metabolomics method based on liquid chromatography-mass spectrometry: insights into the underlying mechanisms of salinity-alkalinity exposures-induced metabolites changes in Barbus capito.

It is critical to investigate the adaptive development and the physiologic mechanism of fish in external stimulation. In this study, the response of Barbus capito to salinity-alkalinity exposures was explored by high-throughput non-targeted and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to investigate metabolic biomarker and pathway changes. Meanwhile, the biochemical indexes of Barbus capito were measured to discover the chronic impairment response to salinity-alkalinity exposures. A total of twenty-nine tissue metabolites were determined to deciphering the endogenous metabolic changes of fishes during the different concentration salinity-alkalinity exposures environment, which were mainly involved in the key metabolism including the phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, pyruvate metabolism, citrate cycle and glycerophospholipid metabolism. Finally, we found the amino acid metabolism as key target were associated with the endogenous metabolites and metabolic pathways of Barbus capito to salinity-alkalinity exposures. In conclusion, metabolomics is a potentially powerful tool to unveil the mechanism information of fish in various exposure environments. This article is protected by copyright. All rights reserved.
Defining the critical period of hedgehog pathway inhibitor‐induced cranial base dysplasia in mice

The hedgehog signaling pathway is critical for developmental patterning of the limb, craniofacial and axial skeleton. Disruption of this pathway in mice leads to a series of structural malformations, but the exact role and critical period of the Hh pathway in the early development of the cranial base have been rarely described.
Cardiovascular magnetic resonance imaging in the UK Biobank: a major international health research resource

Abstract The UK Biobank (UKB) is a health research resource of major international importance, incorporating comprehensive characterization of >500 000 men and women recruited between 2006 and 2010 from across the UK. There is prospective tracking of health outcomes for all participants through linkages with national cohorts (death registers, cancer registers, electronic hospital records, and primary care records). The dataset has been enhanced with the UKB imaging study, which aims to scan a subset of 100 000 participants. The imaging protocol includes magnetic resonance imaging of the brain, heart, and abdomen, carotid ultrasound, and whole-body dual X-ray absorptiometry. Since its launch in 2015, over 48 000 participants have completed the imaging study with scheduled completion in 2023. Repeat imaging of 10 000 participants has been approved and commenced in 2019. The cardiovascular magnetic resonance (CMR) scan provides detailed assessment of cardiac structure and function comprising bright blood anatomic assessment (sagittal, coronal, and axial), left and right ventricular cine images (long and short axes), myocardial tagging, native T1 mapping, aortic flow, and imaging of the thoracic aorta. The UKB is an open access resource available to health researchers across all scientific disciplines from both academia and industry with no preferential access or exclusivity. In this paper, we consider how we may best utilize the UKB CMR data to advance cardiovascular research and review notable achievements to date.
G protein-coupled estrogen receptor-1: homology modeling approaches and application in screening new GPER-1 modulators

Abstract G protein-coupled receptors (GPCRs) belong to the largest family of protein targets comprising over 800 members in which at least 500 members are the therapeutic targets. Among the GPCRs, G protein-coupled estrogen receptor-1 (GPER-1) has shown to have the ability in estrogen signaling. As GPER-1 plays a critical role in several physiological responses, GPER-1 has been considered as a potential therapeutic target to treat estrogen-based cancers and other non-communicable diseases. However, the progress in the understanding of GPER-1 structure and function is relatively slow due to the availability of a only a few selective GPER-1 modulators. As with many GPCRs, the X-ray crystal structure of GPER-1 is yet to be resolved and thus has led the researchers to search for new GPER-1 modulators using homology models of GPER-1. In this review, we aim to summarize various approaches used in the generation of GPER-1 homology model and their applications that have resulted in new GPER-1 ligands. Highlights Features and role of homology modeling in structure. Approaches to model structure. Application of the homology model for the identification of new ligand. Communicated by Ramaswamy H. Sarma
Monocapped tris(dioxime) complexes of technetium(III): synthesis and structural characterization of TcX(dioxime)3B-R (X = Cl, Br; dioxime = dimethylglyoxime, cyclohexanedione dioxime; R = CH3, C4H9)

Monocapped boronic acid adducts of technetium tris(dioxime) complexes (BATO), TcX(dioximeH){sub 2}(dioxime)B-R, where X = Cl or Br, dioxime = cyclohexanedione dioxime or dimethylglyoxime, and R = methyl or butyl, have been prepared by template synthesis starting with pertechnetate and stannous ion, (N(C{sub 4}H{sub 9}){sub 4})(TcOCl{sub 4}), or M{sub 2}(TcX{sub 6}) (M = NH{sub 4}, K; X = Cl, Br). These seven-coordinate Tc(III) compounds are the first examples of tris(dioxime) complexes in which one and only one oxygen of each of the three dioximes is joined to a common cap atom (boron). The crystal structures of three of the BATO complexes have been determined and are reported. The three dioxime oxygens on the uncapped end of the molecule are intramolecularly hydrogen bonded to two bridging protons. A halogen occupies the seventh coordination site. 34 refs., 4 figs., 8 tabs.
Effectiveness of a nutrition education and counselling training package on antenatal care: a cluster randomized controlled trial in Addis Ababa

Abstract The World Health Organization (WHO) recommends the need for a strong nutrition training package for practitioners, including antenatal care (ANC) providers. Without such a training package, ANC visits remain a missed opportunity to address nutritional problems among pregnant women. This study evaluated the effectiveness of an in-service nutrition education and counselling package on the providers’ counselling skills during ANC visits. A cluster randomized controlled trial was conducted in Addis Ababa, Ethiopia. All health-care providers working in ANC units across 20 health centres participated in this study. Health centres were allocated to intervention and control arms using a matched-pair randomization technique. An in-service nutrition education and counselling package, including training for ANC providers, supportive supervision and provision of modules, pamphlets and job aids, was provided for health centres assigned to the intervention arm. Observation checklists were used to assess the counselling skills of health-care providers. We used mixed-effect linear regression to evaluate the impact of the intervention. Significantly more health-care providers in the intervention arm informed pregnant women about the need to have one additional meal (Difference in proportion [DP] 49.17% vs −0.84%; DID 50.0%), about minimum required dietary diversity (DP 72.5% vs −2.5%; DID 75.0%) and about gestational weight gain (DP 68.33% vs −8.33%; DID 76.6%). Furthermore, providers improved in identifying key difficulties that pregnant women face (DP 28.34% vs −2.5%; DID 30.8%), and in recommending simple achievable actions on nutrition during pregnancy (DP 20.8% vs −10.9%; DID 31.6%). The intervention did not have statistically significant effects on how providers informed women about early initiation of breastfeeding (DP 6.67% vs 9.17%; DID −2.5%). The comprehensive in-service nutrition education and counselling package improved how ANC providers engaged with pregnant women and delivered nutrition messages during ANC consultations. This trial was registered in the Pan African Clinical Trial (PACTR registry, PACTR20170900 2477373; Date issued 21 September 2017).
Network Medicine In Cardiovascular Research.

The ability to generate multi-omics data coupled with deeply characterizing the clinical phenotype of individual patients promises to improve understanding of complex cardiovascular pathobiology. There remains an important disconnection between the magnitude and granularity of these data and our ability to improve phenotype-genotype correlations for complex cardiovascular diseases. This shortcoming may be due to limitations associated with traditional reductionist analytical methods, which tend to emphasize a single molecular event in the pathogenesis of diseases more aptly characterized by crosstalk between overlapping molecular pathways. Network medicine is a rapidly growing discipline that considers diseases as the consequences of perturbed interactions between multiple interconnected biological components. This powerful integrative approach has enabled a number of important discoveries in complex disease mechanisms. In this review, we introduce the basic concepts of network medicine and highlight specific examples by which this approach has accelerated cardiovascular research. We also review how network medicine is well-positioned to promote rational drug design for patients with cardiovascular diseases, with particular emphasis on advancing precision medicine.
Improving Patient Preparedness and Confidence in Discussing Advance Directives for End-of-Life Care with Health Care Providers in the United States and Japan

Background The low completion rate of advance directives (ADs) has received attention in Japan and the United States, as policy makers and health care professionals face aging populations with multiple comorbidities. Among the barriers to AD planning, cultural values and attitudes appear to be particularly influential. A comparison of culturally distinct societies provides a deeper understanding of these barriers. Through such an approach, this study identifies strategies for increasing AD planning among late-middle-age Japanese and US individuals. Methods After giving informed consent for the Institutional Review Board–approved study, Japanese and US respondents (45–65 y; 50% female) without ADs completed a language-appropriate online survey. Participants were asked to review a decision aid as part of a scenario-based physician consultation regarding artificial nutrition and hydration (ANH). Hypotheses were analyzed using multigroup structural equation modeling. Results Important similarities were identified across the 2 groups. After reviewing the decision aid, both samples strongly preferred “no ANH. ” Respondents who strongly valued either self-reliance or interpersonal relationships experienced greater preparedness for AD planning. In both countries, greater decision preparedness and positive death attitude predicted greater confidence to discuss care options with a provider. Finally, cultural values predicted preference for family participation: respondents with a strong interdependent self-concept desired more family involvement, whereas high independents preferred less. Conclusions Findings indicate the importance of documenting care preferences and accounting for individual differences. To increase AD adoption, providers should identify patient segments likely to benefit most from the interventions. Targeting individuals in both countries who value self-reliance and interpersonal relationships appears to be a good place to begin. Such individuals can be identified clinically through administration of validated measures used in this study.
Perspectives on Pain, Engagement in HIV Care, and Behavioral Interventions for Chronic Pain Among Older Sexual Minority Men Living with HIV and Chronic Pain: A Qualitative Analysis.

OBJECTIVE AND METHODS The transition of HIV from an acute, fatal illness to a chronic health condition has shifted the treatment needs of people living with HIV (PLWH). PLWH, including sexual minority men (SMM), are living longer and are subject to health concerns often associated with aging. A major health concern of older SMM living with HIV who report problematic substance use is chronic pain. This qualitative analysis of 15 one-on-one interviews with older SMM living with HIV and chronic pain aimed to characterize this population's experiences with pain, engagement in HIV care, and problematic substance use. This study was conducted in a community health center in Boston, MA. We also solicited suggestions for preferred intervention strategies. RESULTS Three main themes emerged from the interview transcripts: 1) the impact of chronic pain and pain treatment on engagement in HIV clinical care; 2) the impact of substance use on chronic pain; and 3) response to interventions to address chronic pain and substance use. CONCLUSIONS These findings underscore the need for interventions that address the structural, physical, and psychological barriers to engagement in medical and self-care that affect older SMM living with HIV and chronic pain.
Adjacent and Non-Adjacent Word Contexts Both Predict Age of Acquisition of English Words: A Distributional Corpus Analysis of Child-Directed Speech

Children show a remarkable degree of consistency in learning some words earlier than others. What patterns of word usage predict variations among words in age of acquisition? We use distributional analysis of a naturalistic corpus of child-directed speech to create quantitative features representing natural variability in word contexts. We evaluate two sets of features: One set is generated from the distribution of words into frames defined by the two adjacent words. These features primarily encode syntactic aspects of word usage. The other set is generated from non-adjacent co-occurrences between words. These features encode complementary thematic aspects of word usage. Regression models using these distributional features to predict age of acquisition of 656 early-acquired English words indicate that both types of features improve predictions over simpler models based on frequency and appearance in salient or simple utterance contexts. Syntactic features were stronger predictors of children's production than comprehension, whereas thematic features were stronger predictors of comprehension. Overall, earlier acquisition was predicted by features representing frames that select for nouns and verbs, and by thematic content related to food and face-to-face play topics; later acquisition was predicted by features representing frames that select for pronouns and question words, and by content related to narratives and object play.
Penetration, distribution, and elimination of remofuscin/soraprazan in Stargardt mouse eyes following a single intravitreal injection using pharmacokinetics and transmission electron microscopic autoradiography: Implication for the local treatment of Stargardt’s disease and dry age‐related macular d

Age‐related macular degeneration (AMD) is the leading cause of blindness in older people in the developed world while Stargardt's disease (SD) is a juvenile macular degeneration and an orphan disease. Both diseases are untreatable and are marked by accumulation of lipofuscin advancing to progressive deterioration of the retinal pigment epithelium (RPE) and retina and subsequent vision loss till blindness. We discovered that a small molecule belonging to the tetrahydropyridoether class of compounds, soraprazan renamed remofuscin, is able to remove existing lipofuscin from the RPE. This study investigated the drug penetration, distribution, and elimination into the eyes of a mouse model for increased lipofuscinogenesis, following a single intravitreal injection. We measured the time course of concentrations of remofuscin in different eye tissues using high‐performance liquid chromatography combined with mass spectroscopy (HPLC‐MS). We also visualized the penetration and distribution of 3H‐remofuscin in eye sections up to 20 weeks post‐injection using transmission electron microscopic (TEM) autoradiography. The distribution of silver grains revealed that remofuscin accumulated specifically in the RPE by binding to the RPE pigments (melanin, lipofuscin and melanolipofuscin) and that it was still detected after 20 weeks. Importantly, the melanosomes in choroidal melanocytes only rarely bind remofuscin emphasizing its potential to serve as an active ingredient in the RPE for the treatment of SD and dry AMD. In addition, our study highlights the importance of electron microscopic autoradiography as it is the only method able to show drug binding with a high intracellular resolution.
Role of endothelial function determined by asymmetric dimethylarginine in the prediction of resistant hypertension: A subanalysis of ReHOT trial

The authors conducted a subanalysis of the ReHOT (Resistant Hypertension Optimal Treatment) study to evaluate the association between endothelial dysfunction and resistant hypertension in a population of patients treated in a staged fashion for hypertension. One hundred and three hypertensive patients were followed for 6 months and participated in seven visits (V0‐V6) 28 days apart. There was a first phase (V0‐V3) of antihypertensive adjustment with three drugs and determination of resistant hypertension and a second randomized phase (V3‐V6) of treatment with a fourth drug (clonidine or spironolactone) in the hypertensive patients characterized as resistant. Of the 103 patients included, 86 (83.5%) underwent the randomization visit (V3), 71 were characterized as non‐resistant hypertensives (82.5%), and 15 as resistant hypertensives (17.5%). Serum asymmetric dimethylarginine (ADMA) was shown to be an independent predictor of resistant hypertension after adjustment for multiple variables (OR: 11.42, 95% CI: 1.02‐127.71, P = .048), and in addition, there was a reduction in blood pressure levels and ADMA values during follow‐up with a positive correlation in both groups and a greater reduction in the group of resistant hypertensives. We demonstrated that ADMA was an independent predictor of resistant hypertension, and we observed that the improvement in blood pressure levels obtained with the treatment was proportional to the reduction in ADMA values, suggesting a complementary role of ADMA not only as a stratification tool for the occurrence of resistant hypertension, but also as a possible therapeutic target in this population.
Should the Biopsychosocial Model Be Considered in Systemic Autoimmune Diseases? Comment on the Article by Posada et al

We read with interest the study by Posada et al. (1) evaluating the therapeutic effects of RSLV-132 (a new RNase compound) in patients with primary Sjogren syndrome (pSS). At first glance, one may be surprised by the enthusiastic conclusion of authors in spite of a biological effect opposite to what was expected, namely an increased expression of interferon (IFN)-stimulated genes (ISG), while pSS is considered as an acquired interferonopathy. However, therapeutic trials are also a unique opportunity to learn about the pathogenesis of such complex condition. Indeed, this study showed a significant improvement of fatigue (measured by various validated scales) in treated patients, surprisingly correlated with the increased expression of ISG.