Miracle-dz/UniFAR-FTUs huggingface dataset:
SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

Accelerate lung repair in SARS‐CoV‐2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS‐CoV‐2 infection. COVID‐19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10+ ILC2 emerge as relevant contributors to SARS‐CoV‐2 pneumonia recovery.
A highly multiplexed quantitative phosphosite assay for biology and preclinical studies

Reliable methods to quantify dynamic signaling changes across diverse pathways are needed to better understand the effects of disease and drug-treatment in cells and tissues but are presently lacking. Here we present SigPath, a targeted mass spectrometry (MS) assay that measures 284 phosphosites in 200 phosphoproteins of biological interest. SigPath probes a broad swath of signaling biology with high throughput and quantitative precision. We applied the assay to investigate changes in phospho-signaling in drug-treated cancer cell lines, breast cancer preclinical models and human medulloblastoma tumors. In addition to validating previous findings, SigPath detected and quantified a large number of differentially regulated phosphosites newly associated with disease models and human tumors at baseline or with drug perturbation. Our results highlight the potential of SigPath to monitor phosphoproteomic signaling events and to nominate mechanistic hypotheses regarding oncogenesis, response and resistance to therapy.
Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

Background: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer’s disease pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment. Objective: The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50–70 years with normal levels of amyloid-β and tau cerebrospinal fluid (CSF) biomarkers. Methods: The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-β and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable. Results: We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected. Conclusion: The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.
Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.
Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes

Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.
Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer

Background Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. Purpose Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. Results Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. Conclusion This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.
Evaluation of a patient self-medication program in allogeneic hematopoietic stem cell transplantation

Introduction Patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discharged with multiple new medications. At our institution, a new patient Self Medication Program (SMP) was implemented on the allo-HSCT units. An SMP allows patients to practice self-administration of medications in a controlled environment before discharge. We assessed the impact of the SMP on patient medication knowledge, self-efficacy, adherence, and safety. Patient and staff satisfaction with the SMP was also explored. Methods Participants in the SMP group received medication counseling by a pharmacist and self-managed their medications with nursing supervision until discharge. Participants in the pre-SMP group received medication counseling by a pharmacist at discharge. All participants completed a Medication Knowledge and Self-Efficacy Questionnaire before discharge and at follow-up. Safety endpoints were assessed for SMP participants. Results Twenty-six patients in the pre-SMP group and 25 patients in the SMP group completed both questionnaires. Median knowledge scores in the pre-SMP group versus the SMP group were 8.5/10 versus 10/10 at discharge (p = 0.0023) and 9/10 versus 10/10 at follow-up (p = 0.047). Median self-efficacy scores were 38/39 in the pre-SMP group versus 39/39 in the SMP group at both discharge and follow-up (pdischarge = 0.11, pfollow-up = 0.10). The SMP was associated with at least 1 medication event in 7 participants, but no medication incidents. Patient and staff surveys showed a positive perceived value of the SMP. Conclusion Our results demonstrate that the SMP is associated with durable, improved medication knowledge, a trend towards improved self-efficacy, and largely positive perceptions among both staff and patient participants.
Did Emergency Department Visits in Infants and Young Children Increase in the Last Decade?

Objectives The aims of the study were to measure overall trends and to identify leading causes for pediatric emergency department (ED) visits among children aged 0 to 4 years. Methods We conducted an 11-year population-based open cohort study using health administrative data from 2008 to 2018 in Ontario, Canada. All ED visits were extracted from the National Ambulatory Care Reporting System, along with the most responsible cause of each visit. Annual ED visit rates were calculated per 100 children in each year. Overall and disease-specific rates for all children were calculated and then stratified by sex and age groups. Relative percentage change in rates between 2008 and 2018 were calculated and compared using standardized differences (SDIFs). Statistical significance of time trends was tested using Poisson regression. Results This study included an average of 911,566 children from 2008 to 2018. All-cause ED visit rates increased by 28.2% from 2008 to 2018 (43.24–55.42 per 100, SDIF >0.1). Respiratory diseases were consistently the top cause of ED visits, and contributed to 1 in 3 ED visits in 2018. These respiratory conditions include asthma, asthma-related diseases (bronchiolitis, bronchitis, influenza, and pneumonia), and other respiratory diseases. Respiratory ED visit rates increased by 32.8% from 2008 to 2018 (11.51–15.28 per 100, SDIF <0.1), driven by a 46.4% (14.58–21.35 per 100, SDIF >0.1) increase among children younger than 1 year. There was a 78.0% increase in ED visits for bronchiolitis in infants (1.45–2.58 per 100, SDIF <0.1). Conclusions Respiratory diseases like bronchiolitis among infants were the consistent leading cause for ED visits. All-cause ED visit rates among young children increased by 28.17% from 2008 to 2018.
Symptoms of major depressive disorder during the COVID-19 pandemic: results from a representative sample of the Canadian population.

INTRODUCTION Since the outbreak of COVID-19, numerous studies from around the world have reported declines in mental health. However, most of these studies were of low-to-moderate quality and many were based on convenience samples or used mental health measures with low validity, or both. Consequently, it has been difficult to draw conclusions. METHODS Both the 2020 Survey on COVID-19 and Mental Health (SCMH) and the Canadian Community Health Survey (CCHS) (2015-2019) used the Patient Health Questionnaire-9 to screen for major depressive disorder (MDD) in adults aged 18 or older. The prevalence of MDD was compared between the SCMH and the CCHS. Risk and protective factors for MDD in the SCMH were examined using bivariate and logistic regression analyses. RESULTS Based on SCMH data, 15.2% (95% CI: 14.2-16.2) of Canadians screened positive for MDD. The prevalence of MDD was more than two times higher in the SCMH (during COVID-19) than in the CCHS (predating COVID-19). In bivariate analysis, Canadians reporting five or more COVID-19-related risk factors were close to 30 times more likely to have MDD than those reporting no risk factors. Mastery and a sense of community belonging were protective factors for MDD. CONCLUSION After remaining stable for two decades, the prevalence of depression among Canadians increased substantially with the onset of COVID-19. Ongoing monitoring of this common condition associated with major morbidity is vital to determine if elevated levels of MDD persist as we progress through and beyond future waves of COVID-19.
Effects of Lifestyle Modification on Patients With Resistant Hypertension

Supplemental Digital Content is available in the text. Background: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. Methods: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. Results: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (–12.5 [95% CI, –14.9 to –10.2] mm Hg) compared with SEPA(–7.1 [–95% CI, 10.4 to –3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (–7.0 [95% CI, –8.5 to –4.0] mm Hg), with no change in SEPA (–0.3 [95% CI, –4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus –1.1 ms/mm Hg [95% CI, –2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus –0.2 ln ms2 [95% CI, –0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, –0.3 to 1.0] versus –1.4% [95% CI, –2.5 to –0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). Conclusions: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT02342808.
Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus

Background and Aims This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. Methods A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. Results The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002–2011 to 12% in 2012–2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III–V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. Conclusion Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.
The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis

Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω‐oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR‐Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long‐chain DCAs, increased urine medium‐chain DCAs, lipodystrophy, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial fatty acid β‐oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.
Well-Being and Mental Health of Students during the COVID-19 Pandemic

Background: During the COVID-19 pandemic, a decrease in well-being and an increase in mental health problems were registered in medical and psychotherapeutic practices, counseling centers, and clinics. According to previous studies, younger people and women seemed to be particularly affected. The aim of this study was to describe mental health problems of students and to draw consequences for the further handling of pandemics and other crises. Method: Students at the University of Heidelberg, a typical German “full university,” were surveyed online using internationally comparable screening instruments like the Well-Being Index (WHO-5) and the Patient Health Questionnaire (PHQ). In addition, the students had the opportunity to describe in a narrative form their well-being and to make suggestions how to improve their situation. Results: Out of a population of 27,162 students who were contacted by email, 2,137 students completed the questionnaire. The salient finding is that according to the WHO-5 Well-Being Index, 72.2% of the respondents feel seriously impaired in their well-being. This corresponds to the finding that 75.8% of the respondents in the PHQ-D show indications of at least one syndrome diagnosis. Depression was found in 41.8% of the respondents in the PHQ-D. Indications of moderate to severe and severe depressive syndromes were present in 31.8%. Signs of somatoform syndromes are found in 25.4% and of anxiety syndromes in 20.0%. 1,089 students gave narrative reports on how they were feeling and made suggestions for improvement. About 75% reported severely reduced well-being. Their main complaints were loneliness and depression and lack of recognition for their specific academic and life situation during the pandemic. By far, the largest proportion of students supposed that their mental health issues were caused and/or intensified by the pandemic-related social contact restrictions. The vast majority of them made reasonable suggestions for controlled relaxation of contact restrictions. Conclusions: Students suffer severely from the pandemic-related social restriction. In respect to future pandemic outbreaks or other crises leading to social isolation, the dramatic consequences of social lockdowns should be taken into account. Under pandemic conditions, we especially should support persons lacking social networks.