Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-Reported Modifiable Risk Factors of Cardiovascular Disease among Seafarers: A Cross-Sectional Study of Prevalence and Clustering

Background: Cardiovascular diseases (CVD) are the major cause of work-related mortality from diseases onboard ships in seafarers. CVD burden derives mainly from modifiable risk factors. To reduce the risk factors and the burden of CVD onboard ships in seafarers, it is important to understand the up-to-date prevalence of modifiable risk factors. The primary purpose of this study was to assess the prevalence and clustering of self-reported modifiable CVD risk factors among seafarers. We have also explored the association between socio-demographic and occupational characteristics and reported modifiable CVD risk factor clustering. Materials and methods: A cross-sectional study was conducted among seafarers from November to December 2020 on board ships. In total, 8125 seafarers aged 18 to 70 were selected from 400 ships. Data were collected using a standardized and anonymous self-reported questionnaire. The prevalence value for categorical variables and mean differences for continuous variables were compared using chi-square and independent sample t-tests. Multinomial logistic regression models were performed to identify independent predictors for modifiable CVD risk factor clustering. Results: Out of a total of 8125 seafarers aged ≥18 years on selected vessels, 4648 seafarers volunteered to participate in the survey, with a response rate of 57.2%. Out of 4318 participants included in analysis, 44.7% and 55.3% were officers and non-officers, respectively. The prevalence of reported hypertension, diabetes, current smoking and overweight or obesity were 20.8%, 8.5%, 32.5%, and 44.7%, respectively. Overall, 40%, 20.9%, 6% and 1.3% of the study participants respectively had one, two, three and four modifiable CVD risk factors. Older age (51+ years) (odds ratio (OR): 3.92, 95% confidence interval (CI): 2.44–6.29), being non-officers (OR: 1.36, 95% CI: 1.09–1.70), job duration (10–20 years) (OR: 2.73, 95% CI: 2.09–3.57), job duration (21+ years) (OR: 2.60, 95% CI: 1.79–3.78), working 57–70 h per week (OR: 2.03, 95% CI: 1.65–2.49) and working 71+ h per week (OR: 3.08, 95% CI: 2.42–3.92) were independent predictors for at least two self-reported modifiable CVD risk factor clustering. Conclusion: The results of our study demonstrate that more than four in six (68.5%) seafarers aged between 19 and 70 years have at least one of the modifiable CVD risk factors. Therefore, CVD prevention and modifiable risk factors reduction strategies targeting high-risk groups should be designed and implemented on board ships.
Direct detection of ESKAPEc pathogens from whole blood using the T2Bacteria Panel allows early antimicrobial stewardship intervention in patients with sepsis

In the microbiological diagnosis of bloodstream infections (BSI), blood culture (BC) is considered the gold standard test despite its limitations such as low sensitivity and slow turnaround time. A new FDA‐cleared and CE‐marked platform utilizing magnetic resonance to detect amplified DNA of the six most common and/or problematic BSI pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli; referred to as ESKAPEc) is available and may shorten the time to diagnosis and potentially improve antimicrobial utilization. Whole blood samples from hospitalized patients with clinical signs of sepsis were analyzed using the T2Bacteria Panel (T2Biosystems) and compared to simultaneously collected BC. Discrepant results were evaluated based on clinical infection criteria, combining supporting culture results and the opinion of treating physicians. A total of 55 samples from 53 patients were evaluated. The sensitivity and specificity of the T2Bacteria panel was 94% (16 out of 17 detections of T2Bacteria‐targeted organisms) and 100%, respectively, with 36.4% (8 of 22) causes of BSI detected only by this method. The T2Bacteria Panel detected pathogens on average 55 hours faster than standard BC. In our study, 9 of 15 patients with positive T2Bacteria Panel results received early‐targeted antibiotic therapy and/or modification of antimicrobial treatment based on T2Bacteria Panel findings. Given the high reliability, faster time to detection, and easy workflow, the technique qualifies as a point‐of‐care testing approach.
Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma

Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients.
HLA-G and HLA-E Immune Checkpoints Are Widely Expressed in Ewing Sarcoma but Have Limited Functional Impact on the Effector Functions of Antigen-Specific CAR T Cells

Simple Summary Solid cancers can effectively counteract immune attack by inhibitory checkpoints in the tumor microenvironment. Blockade of relevant immune checkpoints could be a useful tool for enhancing the efficacy of antitumor T cell therapies. Here, we studied the capacity of two nonclassical HLA molecules with known immunosuppressive function, HLA-G and HLA-E, to prevent antigen-specific immune effector functions of gene-engineered T cells against Ewing sarcoma. Inflammatory conditions and interactions of Ewing sarcoma cells with antitumor T cells reliably induced upregulation of the two molecules on the tumor cells. Moreover, as previously shown for HLA-G, HLA-E was detected in a high proportion of human Ewing sarcoma biopsies. However, artificial expression of either of the two molecules on Ewing sarcoma cells failed to reduce cytolytic and activation responses of antigen-specific T cells. We conclude that blockade of HLA-G and HLA-E immune checkpoints is not a promising strategy for enhancing T cell therapies in Ewing sarcoma. Abstract Immune-inhibitory barriers in the tumor microenvironment of solid cancers counteract effective T cell therapies. Based on our finding that Ewing sarcomas (EwS) respond to chimeric antigen receptor (CAR) gene-modified effector cells through upregulation of human leukocyte antigen G (HLA-G), we hypothesized that nonclassical HLA molecules, HLA-G and HLA-E, contribute to immune escape of EwS. Here, we demonstrate that HLA-G isotype G1 expression on EwS cells does not directly impair cytolysis by GD2-specific CAR T cells (CART), whereas HLA-G1 on myeloid bystander cells reduces CART degranulation responses against EwS cells. HLA-E was induced in EwS cells by IFN-γ stimulation in vitro and by GD2-specific CART treatment in vivo and was detected on tumor cells or infiltrating myeloid cells in a majority of human EwS biopsies. Interaction of HLA-E-positive EwS cells with GD2-specific CART induced upregulation of HLA-E receptor NKG2A. However, HLA-E expressed by EwS tumor cells or by myeloid bystander cells both failed to reduce antitumor effector functions of CART. We conclude that non-classical HLA molecules are expressed in EwS under inflammatory conditions, but have limited functional impact on antigen-specific T cells, arguing against a relevant therapeutic benefit from combining CART therapy with HLA-G or HLA-E checkpoint blockade in this cancer.
The Role of CX3CL1 and ADAM17 in Pathogenesis of Diffuse Parenchymal Lung Diseases

Fractalkine (CX3CL1) is a unique chemokine that functions as a chemoattractant for effector cytotoxic lymphocytes and macrophages expressing fractalkine receptor CX3CR1. CX3CL1 exists in two forms—a soluble and a membrane-bound form. The soluble CX3CL1 is released from cell membranes by proteolysis by the TNF-α-converting enzyme/disintegrin-like metalloproteinase 17 (TACE/ADAM17) and ADAM10. In this study, we evaluated the diagnostic relevance and potential roles of CX3CL1 and ADAM17 in the pathogenesis of diffuse parenchymal lung diseases (DPLDs) in the human population. The concentration of CX3CL1 and ADAM17 was measured by the enzyme-linked immunosorbent assay (ELISA) test in bronchoalveolar lavage fluids of patients suffering from different DPLDs. The concentration of CX3CL1 was significantly higher in patients suffering from idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis patients compared to the control group. A significantly higher concentration of CX3CL1 was measured in fibrotic DPLDs compared to non-fibrotic DLPD patients. We found a positive correlation of CX3CL1 levels with the number of CD8+ T cells, and a negative correlation with CD4+ T cells in BALF and diffusion capacity for carbon monoxide. The concentration of ADAM17 was significantly lower in the IPF group compared to the other DPLD groups. We noticed a significantly higher CX3CL1/ADAM17 ratio in the IPF group compared to the other DPLD groups. We suggest that CX3CL1 has a distinctive role in the pathogenesis of DPLDs. The level of CX3CL1 strongly correlates with the severity of lung parenchyma impairment. The results suggest that high values of CX3CL1/ADAM17 could be diagnostic markers for IPF.
Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells

In recent decades, type 2 diabetes complications have been correlated with amylin aggregation, copper homeostasis and metformin side effects. However, each factor was analyzed separately, and only in some rare cases copper/amylin or copper/metformin complexes were considered. We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane. Considering the increased concentration of amylin, copper (II) and metformin in kidneys of T2DM patients, our findings on the toxicity of amylin and its adducts may be correlated with diabetic nephropathy development.
Impacts of Dietary Supplementations of Orange Peel and Tomato Pomace Extracts as Natural Sources for Ascorbic Acid on Growth Performance, Carcass Characteristics, Plasma Biochemicals and Antioxidant Status of Growing Rabbits

Simple Summary There has been growing interest in using natural feed additives in to enhance animal performance and meat quality for human consumption. Citrus fruit residues can act as potential natural resources of antioxidants, which comprise a considerable quantity of ascorbic acid. Tomato pomace powder has a good nutritional value because of its content of essential amino acids and fatty acids besides its high content of antioxidants. This work examined the impact of dietary orange peel and tomato pomace extract supplementations at level of 200 mg/kg on growth performance, plasma biochemicals, carcass characteristics and antioxidant status of growing male rabbits. Dietary supplementations of orange peel and tomato pomace extracts could effectively improve growth performance, antioxidative status, modulate ascorbic acid level in plasma and meat and lower the plasma total cholesterol. Abstract The effect of dietary orange peel (OPE) and tomato pomace extract (TPE) supplementations on growth performance, plasma biochemicals, carcass characteristics and antioxidant status of growing male rabbits were investigated. A total of 96 rabbits (5 weeks old) were distributed into four groups. The first group received untreated pelleted diet (control). The second group was fed a diet containing ascorbic acid (AA; 1.0 g/kg diet), while the third and fourth groups consumed diets supplemented with 200 gm of OPE or (TPE, respectively. Our results indicated that OPE and TPE contained 59, 14.03 mg ascorbic acid/100 g DM, respectively. Growth performance, except feed conversion ratio, and carcass weight were improved by dietary supplementations. Dietary supplementations decreased kidneys, abdominal, back fats and ether extract of meat. Plasma protein and globulin levels were high in rabbits fed AA and TPE-supplemented diets. Low plasma total cholesterol and LDL-cholesterol concentrations were observed in rabbits fed the supplemented diets. Plasma AA was increased in rabbits fed AA and OPE-supplemented diets. Rabbits fed OPE and TPE-supplemented diets had great SOD activity. The best economic efficiency was recorded by rabbits fed the supplemented diets. Dietary supplementations of OPE and TPE could effectively improve growth performance, antioxidative status, modulate AA level in plasma and meat and lower plasma total cholesterol and LDL.
Effects of Dietary Supplementation of Acetate and L-Tryptophan Conjugated Bypass Amino Acid on Productivity of Pre- and Post-Partum Dairy Cows and Their Offspring

Simple Summary This study examined the effect of acetate and L-tryptophan-conjugated bypass amino acid (ACT), supplemented (15 g/day) to Holstein cows during late pregnancy, on their productivity and the performance of offspring. We identified that the supplementation of ACT incorporated into diet was beneficial for improving the feed intake, blood hematology, and metabolites of the prepartum, and also had a positive effect on reducing saturated fatty acids in the colostrum of the cows postpartum and on the body weight of the newborn calves. The results of this study suggest that ACT supplementation improves the productivity of dairy cows. Abstract In this study, we investigated the effect of dietary supplementation with acetate and L-tryptophan-conjugated bypass amino acid (ACT) during late pregnancy on the production performance of cows pre- and postpartum and their offspring. Eight multiparous Holstein cows (calving date ±15 d, 2nd parity; n = 4) were supplied with diets without ACT supplementation (Control) or with 15 g/day ACT supplementation (ACT). The results showed that ACT improved the feed intake (FI) in dry cows. No differences in blood hematological parameters were found between the two groups of prepartum cows. The serum glutamic-oxaloacetic transaminase activity increased and the triglyceride concentration decreased in the ACT-treated group compared to the control group. In the postpartum cows, milk compositions were not affected by ACT supplementation. Saturated fatty acid (SFA) content in the colostrum was significantly lower in the ACT-treated group than in the control group. Serum glucose (GLC) level was significantly higher in the ACT-treated group than in the control group. Monocyte and GLC levels were lower in calves of groups where their dams had received ACT. Overall, we found higher FI in the dry cows, lower colostrum SFA levels, and heavier calf birth weight (5.5 kg) when the dams were supplemented with ACT, suggesting a positive nutrient compensation by ACT supplementation to dry cows.
Profile of Prescription Medication in an Internal Medicine Ward

Aging-related loss of resilience associated with the lack of evidence regarding the therapeutic efficacy of medicines can prompt a lack of efficacy of treatments and multiple prescriptions. This work aims to characterize the medication profile of Portuguese older adult inpatients and explore the relationship between hospitalization days and the consumption of medicines. A retrospective data analysis study in older patients who were admitted to a medical internal medicine ward during 2019. The median age of the 616 patients included was 85 years. During the hospitalized period, patients took on average 18.08 medicines. The most prescribed drugs belong to the subgroup of (a) anti-thrombotic agents (6.7%), with enoxaparin being the most prescribed, (b) other analgesics and antipyretics (6.6%), paracetamol being the most frequent, and (c) the Angiotensin Conversion Enzyme Inhibitor (ACE) (6.5%), captopril being the most frequent. The high number of prescriptions in older adults during their hospitalization suggests the need of changing therapeutics to achieve a better efficacy of treatment, which corroborates the hypothesis that the lack of scientific evidence concerning the risk/benefits of many medical therapies in older adults can make it difficult to achieve good clinical outcomes and promote the wastage of health resources.
Severe Fever with Thrombocytopenia Syndrome in Cats and Its Prevalence among Veterinarian Staff Members in Nagasaki, Japan

In this study, we investigated severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection in cats in Nagasaki, Japan. In total, 44 of 133 (33.1%) cats with suspected SFTS were confirmed to be infected with SFTSV. Phylogenetic analyses of SFTSV isolates from cats indicated that the main genotype in Nagasaki was J1 and that unique reassortant strains with J2 (S segment) and unclassified genotypes (M and L segments) were also present. There were no significant differences in virus growth in cell cultures or fatality in SFTSV-infected mice between the SFTSV strains that were isolated from recovered and fatal cat cases. Remarkably, SFTSV RNAs were detected in the swabs from cats, indicating that the body fluids contain SFTSV. To evaluate the risk of SFTSV infection when providing animal care, we further examined the seroprevalence of SFTSV infection in veterinarian staff members; 3 of 71 (4.2%) were seropositive for SFTSV-specific antibodies. Our results provide useful information on the possibility of using cats as sentinel animals and raised concerns of the zoonotic risk of catching SFTSV from animals.
Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib

BRAFV600E mutations are found in approximately 10% of colorectal cancer patients and are associated with worse prognosis and poor outcomes with systemic therapies. The aim of this study was to identify novel druggable features of BRAFV600E-mutated colon cancer (CC) cells associated with the response and resistance to BRAFV600E inhibitor vemurafenib. Towards this aim, we carried out global proteomic profiling of BRAFV600E mutant vs. KRAS mutant/BRAF wild-type and double wild-type KRAS/BRAF CC cells followed by bioinformatics analyses. Validation of selected proteomic features was performed by immunohistochemistry and in silico using the TCGA database. We reveal an increased abundance and activity of nucleophosmin (NPM1) in BRAFV600E-mutated CC in vitro, in silico and in tumor tissues from colon adenocarcinoma patients and demonstrate the roles of NPM1 and its interaction partner c-Myc in conveying the resistance to vemurafenib. Pharmacological inhibition of NPM1 effectively restored the sensitivity of vemurafenib-resistant BRAF-mutated CC cells by down-regulating c-Myc expression and activity and consequently suppressing its transcriptional targets RanBP1 and phosphoserine phosphatase that regulate centrosome duplication and serine biosynthesis, respectively. Altogether, findings from this study suggest that the NPM1/c-Myc axis could represent a promising therapeutic target to thwart resistance to vemurafenib in BRAF-mutated CC.
The Impact of Intracytoplasmic Sperm Injection in Non-Male Factor Infertility—A Critical Review

Intracytoplasmic sperm injection (ICSI) was originally designed to overcome barriers due to male factor infertility. However, a surveillance study found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. Numerous studies have investigated fertilization rate, total fertilization failure, and live birth rate per cycle (LBR), comparing the use of ICSI versus conventional in vitro fertilization (IVF) for non-male factor infertility. The overwhelming conclusion shows no increase in fertilization rate or LBR per cycle with the use of ICSI for non-male factor infertility. The overuse of ICSI is likely related to the desire to avoid a higher rate of total fertilization failure in IVF. However, data supporting the benefit of using ICSI for non-male factor infertility is lacking, and 33 couples would need to be treated with ICSI unnecessarily to avoid one case of total fertilization failure. Such practice increases the cost to the patient, increases the burden on embryologist’s time, and is a misapplication of resources. Additionally, there remains conflicting data regarding the safety of offspring conceived by ICSI and potential damage to the oocyte. Thus, the use of ICSI should be limited to those with male factor infertility or a history of total fertilization factor infertility due to uncertainties of potential adverse impact and lack of proven benefit in non-male factor infertility.
Systematic Review and Meta-Analysis of the Diagnostic Accuracy of Mobile-Linked Point-of-Care Diagnostics in Sub-Saharan Africa

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as Sub-Saharan Africa (SSA). The advent of Severe acute respiratory syndrome coronavirus 2 has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis. We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full text via EBSCOhost databases, from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and Trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to those of the reference representing the gold standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458–0.541), 0.535 (95% CI: 0.401–0.663), 0.952 (95% CI: 0.60–1.324), 1.381 (95% CI: 0.391–4.879), and 0.944 (95% CI: 0.579–1.538), respectively. Evidence shows that the diagnostic accuracy of mobile-linked POC diagnostics in detecting infections in SSA is presently moderate. Future research is recommended to evaluate mHealth devices’ diagnostic potential using devices with excellent sensitivities and specificities for diagnosing diseases in this setting.