Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma

Simple Summary Data on the prognostic and predictive value of germline cancer predisposing pathogenic/likely pathogenic variants (P/LPVs) in patients with pancreatic ductal adenocarcinoma is limited. This research was a study of germline testing of 62 cancer susceptibility genes in 549 unselected patients with pancreatic cancer. We reported a significant proportion of European patients with pancreatic cancer carrying P/LPVs in clinically significant genes, irrespectively of age, family history or disease stage. Importantly, P/LPVs were identified in pancreatic cancer-associated genes and in homologous recombination repair genes in 4.0% and 7.7% of patients, respectively. The presence of any P/LPVs was associated with improved overall survival univariately; however, it did not retain its independent prognostic significance in multivariate analysis. The presence of P/LPVs in homologous recombination repair genes did not predict benefit from platinum-based treatment. These results should be prospectively validated through universal genetic testing of patients with pancreatic cancer, taking into consideration the administration of newer treatments. Abstract Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated Centers. The main endpoints were prevalence of P/LPVs and overall survival (OS). P/LPVs in PDAC-associated and homologous recombination repair (HRR) genes were identified in 22 (4.0%) and 42 (7.7%) of 549 patients, respectively. P/LPVs were identified in 16 genes, including ATM (11, 2.0%) and BRCA2 (6, 1.1%), while 19 patients (3.5%) were heterozygotes for MUTYH P/LPVs and 9 (1.6%) carried the low-risk allele, CHEK2 p.(Ile157Thr). Patients carrying P/LPVs had improved OS compared to non-carriers (22.6 vs. 13.9 months, p = 0.006). In multivariate analysis, there was a trend for improved OS in P/LPV carriers (p = 0.063). The interaction term between platinum exposure and mutational status of HRR genes was not significant (p-value = 0.35). A significant proportion of patients with PDAC carries clinically relevant germline P/LPVs, irrespectively of age, family history or disease stage. The predictive role of these P/LPVs has yet to be defined. ClinicalTrials.gov Identifier: NCT03982446.
The impact of a 1‐hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure

Co‐treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH‐dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1‐hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady‐state pazopanib trough concentration (Cmin) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) Cmin levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM Cmin levels were lower in GAS users vs non‐GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1‐26.7] vs 28.2 mg/L [95% CI: 25.9‐30.5], P = .015 and 26.0 mg/L [95% CI: 22.4‐30.3] vs 33.5 mg/L [95% CI: 30.3‐37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non‐GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub‐analysis showed lower GM pazopanib Cmin in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non‐users. Our research showed that a 1‐hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.
Analysis of Multidrug Resistance in Staphylococcus aureus with a Machine Learning-Generated Antibiogram

Multidrug resistance (MDR) surveillance consists of reporting MDR prevalence and MDR phenotypes. Detailed knowledge of the specific associations underlying MDR patterns can allow antimicrobial stewardship programs to accurately identify clinically relevant resistance patterns. ABSTRACT Multidrug resistance (MDR) surveillance consists of reporting MDR prevalence and MDR phenotypes. Detailed knowledge of the specific associations underlying MDR patterns can allow antimicrobial stewardship programs to accurately identify clinically relevant resistance patterns. We applied machine learning and graphical networks to quantify and visualize associations between resistance traits in a set of 1,091 Staphylococcus aureus isolates collected from one New York hospital between 2008 and 2018. Antimicrobial susceptibility testing was performed using reference broth microdilution. The isolates were analyzed by year, methicillin susceptibility, and infection site. Association mining was used to identify resistance patterns that consisted of two or more individual antimicrobial resistance (AMR) traits and quantify the association among the individual resistance traits in each pattern. The resistance patterns captured the majority of the most common MDR phenotypes and reflected previously identified pairwise relationships between AMR traits in S. aureus. Associations between β-lactams and other antimicrobial classes (macrolides, lincosamides, and fluoroquinolones) were common, although the strength of the association among these antimicrobial classes varied by infection site and by methicillin susceptibility. Association mining identified associations between clinically important AMR traits, which could be further investigated for evidence of resistance coselection. For example, in skin and skin structure infections, clindamycin and tetracycline resistance occurred together 1.5 times more often than would be expected if they were independent from one another. Association mining efficiently discovered and quantified associations among resistance traits, allowing these associations to be compared between relevant subsets of isolates to identify and track clinically relevant MDR.
Assessment of Suicidal Behaviors Among Individuals With Autism Spectrum Disorder in Denmark.

Importance There is limited evidence supporting an association of autism spectrum disorder (ASD) with suicidality and the risk factors for suicide attempt and suicide among people with ASD. Existing research highlights the need for national cohort studies. Objectives To analyze whether people with ASD have higher rates of suicide attempt and suicide compared with people without ASD using national register data, identify potential risk factors for suicide attempt and suicide among those with ASD, and examine associations with comorbid disorders. Design, Setting, and Participants In this cohort study, nationwide register data from January 1, 1995, to December 31, 2016, were gathered on 6 559 266 individuals in Denmark aged 10 years or older. Statistical analysis was performed from November 20, 2018, to November 21, 2020. Main Outcomes and Measures Rates of suicide attempt and suicide among persons with ASD were compared with rates among persons without ASD, using Poisson regression models to calculate incidence rate ratios adjusted for sex, age, and time period. Results Of the total study population of 6 559 266 individuals, 35 020 individuals (25 718 male [73.4%]; mean [SD] age at diagnosis, 13.4 [9.3] years) received a diagnosis of ASD. A total of 64 109 incidents of suicide attempts (587 [0.9%] among individuals with ASD) and 14 197 suicides (53 [0.4%] among individuals with ASD) were recorded. Persons with ASD had a more than 3-fold higher rate of suicide attempt (adjusted incidence rate ratio [aIRR], 3.19; 95% CI, 2.93-3.46) and suicide (aIRR, 3.75; 95% CI, 2.85-4.92) than those without ASD. For individuals with ASD, the aIRR for suicide attempt among female individuals was 4.41-fold (95% CI, 3.74-5.19) higher compared with male individuals; for individuals without ASD, the aIRR for female individuals was 1.41-fold (95% CI, 1.39-1.43) higher compared with male individuals. Higher rates of suicide attempt were noted across all age groups for those with ASD. Persons with a diagnosis of ASD only had an aIRR of 1.33 (95% CI, 0.99-1.78) for suicide attempt, whereas those with other comorbid disorders had an aIRR of 9.27 (95% CI, 8.51-10.10) for suicide attempt compared with those without any psychiatric disorders. A total of 542 of 587 individuals with ASD (92.3%) who attempted suicide had at least 1 other comorbid condition and 48 of 53 individuals with ASD (90.6%) who died by suicide had at least 1 other comorbid condition. Conclusions and Relevance This nationwide retrospective cohort study found a higher rate of suicide attempt and suicide among persons with ASD. Psychiatric comorbidity was found to be a major risk factor, with more than 90% of those with ASD who attempted or died by suicide having another comorbid condition. Several risk factors are different from the risk factors in the general population, which suggests the need for tailored suicide prevention strategies.
Protective role of rutin against combined exposure to lipopolysaccharide and D-galactosamine-induced dysfunctions in liver, kidney, and brain: Hematological, biochemical, and histological evidences.

Protective efficacy of rutin over liver, kidney, and brain dysfunctions was evaluated in this investigation. Rutin (5, 10, and 20 mg/kg) was administered continuously for 6 days followed by single dose of D-galactosamine (300 mg/kg I.P.) and lipopolysaccharide (50 µg/kg I.P.) on the 6th day. Hematological, serological, biochemical, and histological aspects were considered for this study. One-way ANOVA (p ≤ .05) followed by Tukey's HSD post hoc test determined the statistical significance. Serum AST, ALT, ALP, urea, uric acid, and creatinine were increased significantly, whereas albumin and glucose were significantly decreased after combined exposure to LPS and D-GalN. Glutathione level and activity of SOD and catalase were decreased, whereas lipid peroxidation, triglycerides, and cholesterol were increased in tissue samples due to LPS- and D-GalN-induced toxicity. Prophylactic treatment of rutin maintained studied variables toward control claiming the protective role of rutin. PRACTICAL APPLICATION: Rutin is plenteous in a variety of commonly ingested foods such as onion, wine, grape, citrus fruits, tea, and buckwheat. Rutin supplement is recommended for the treatment of various diseases such as varicose veins, internal bleeding, or hemorrhoids. Rutin is better than well-known antithrombic agent, Juniferdin, or Bacitracin. In the present study, rutin showed protective effects against LPS- and D-GalN-induced multiorgan dysfunctions due to its anti-inflammatory and antioxidant properties. Therefore, rutin may be developed and practiced as a food supplement to cope with acute organ dysfunctions caused by inflammatory and oxidative damage.
Altered Gut Microbiota in Irritable Bowel Syndrome and Its Association with Food Components

The interplay between diet and gut microbiota has gained interest as a potential contributor in pathophysiology of irritable bowel syndrome (IBS). The purpose of this study was to compare food components and gut microbiota patterns between IBS patients and healthy controls (HC) as well as to explore the associations of food components and microbiota profiles. A cross-sectional study was conducted with 80 young adults with IBS and 21 HC recruited. The food frequency questionnaire was used to measure food components. Fecal samples were collected and profiled by 16S rRNA Illumina sequencing. Food components were similar in both IBS and HC groups, except in caffeine consumption. Higher alpha diversity indices and altered gut microbiota were observed in IBS compared to the HC. A negative correlation existed between total observed species and caffeine intake in the HC, and a positive correlation between alpha diversity indices and dietary fiber in the IBS group. Higher alpha diversity and gut microbiota alteration were found in IBS people who consumed caffeine more than 400 mg/d. Moreover, high microbial diversity and alteration of gut microbiota composition in IBS people with high caffeine consumption may be a clue toward the effects of caffeine on the gut microbiome pattern, which warrants further study.
Advance Care Planning among Older Gay Men Living with HIV in Montreal, Canada: Challenges to Thinking and Talking about Future Care

ABSTRACT This qualitative study employed a cross sectional focus group design to explore how older gay men living with HIV, experience, perceive, and engage with advance care planning (ACP). Seven gay men 50+, residing in Montreal, Canada, participated in a focus group that was audio-recorded, transcribed, and thematically analyzed. Findings suggested that social isolation, preoccupations with day-to-day living, and managing disclosures related to sexual orientation and HIV status created barriers to these men’s capacities to think about let alone talk about future care. These findings challenge current conceptualizations of ACP, which position reflection as an individual process that precedes allocating a decision-maker and communicating care preferences. Analyses further revealed that relational connections helped create a space where ACP could occur for participants. Hence, improving the uptake of ACP amongst older gay men with HIV may require interventions that embed such discussions into broader programs aimed at building support and community.
UK university staff experience high levels of sedentary behaviour during work and leisure time

Objective. Reducing sedentary behaviours at work is imperative. Before effective strategies can be developed there is a need to understand profiles of activity within particular roles and organizations. This study aimed to determine activity profiles of staff by job title at a UK university. Methods. Three-hundred and seventeen participants completed the international physical activity questionnaire – short form to determine physical activity profiles. Fifty-one participants also wore a wrist-worn GENEActiv accelerometer for 7 days and completed a self-report diary denoting work and leisure hours. Results. Twenty-one per cent of respondents were categorized as inactive and achieved 298 ± 178 metabolic equivalent minutes (MET-min)/week. Those in administrative roles were most sedentary (501 ± 161 min/day). Accelerometer data highlighted that sedentary time was identical between job roles (pooled mean 8746 ± 823 counts) and equated to 84 ± 9% of total time. During working hours, management, professional and specialist job roles had the highest level of sedentary time (2066 ± 416 counts). Conclusion. Time spent undertaking sedentary activities during working hours contributes to reduced overall activity and can impede productivity, performance and health. Interventions encouraging regular movement and preventing sedentary behaviours at work are therefore required.
Urogenital Schistosomiasis—History, Pathogenesis, and Bladder Cancer

Schistosomiasis is the most important helminthiasis worldwide in terms of morbidity and mortality. Most of the infections occurs in Africa, which about two thirds are caused by Schistosoma haematobium. The infection with S. haematobium is considered carcinogenic leading to squamous cell carcinoma (SCC) and urothelial carcinoma of the urinary bladder. Additionally, it is responsible for female genital schistosomiasis leading to infertility and higher risk of human immunodeficiency virus (HIV) transmission. Remarkably, a recent outbreak in Corsica (France) drew attention to its potential re-mergence in Southern Europe. Thus far, little is known related to host-parasite interactions that trigger carcinogenesis. However, recent studies have opened new avenues to understand mechanisms on how the parasite infection can lead cancer and other associated pathologies. Here, we present a historical perspective of schistosomiasis, and review the infection-associated pathologies and studies on host–parasite interactions that unveil tentative mechanisms underlying schistosomiasis-associated carcinogenesis.
Noninvasive oxygenation assessment after acute myocardial infarction with breathing maneuvers‐induced oxygenation‐sensitive magnetic resonance imaging

The safety profiles when performing stress oxygenation‐sensitive magnetic resonance imaging (OS‐MRI) have raised concerns in clinical practice. Adenosine infusion can cause side effects such as chest pain, dyspnea, arrhythmia, and even cardiac death. The aim of this study was to investigate the feasibility of breathing maneuvers‐induced OS‐MRI in acute myocardial infarction (MI). This was a prospective study, which included 14 healthy rabbits and nine MI rabbit models. This study used 3 T MRI/modified Look‐Locker inversion recovery sequence for native T1 mapping, balanced steady‐state free precession sequence for OS imaging, and phase‐sensitive inversion recovery sequence for late gadolinium enhancement. The changes in myocardial oxygenation (ΔSI) were assessed under two breathing maneuvers protocols in healthy rabbits: a series of extended breath‐holding (BH), and a combined maneuver of hyperventilation followed by the extended BH (HVBH). Subsequently, OS‐MRI with HVBH in acute MI rabbits was performed, and the ΔSI was compared with that of adenosine stress protocol. Student's t‐test, Wilcoxon rank test, and Friedman test were used to compare ΔSI in different subgroups. Pearson and Spearman correlation was used to obtain the association of ΔSI between breathing maneuvers and adenosine stress. Bland–Altman analysis was used to assess the bias of ΔSI between HVBH and adenosine stress. In healthy rabbits, BH maneuvers from 30 to 50 s induced significant increase in SI compared with the baseline (all p < 0.05). By contrast, hyperventilation for 60 s followed by 10 s‐BH (HVBH 10 s) exhibited a comparable ΔSI to that of stress test (p = 0.07). In acute MI rabbits, HVBH 10 s‐induced ΔSIs among infarcted, salvaged, and the remote myocardial area were no less effectiveness than adenosine stress when performing OS‐MRI (r = 0.84; p < 0.05). Combined breathing maneuvers with OS‐MRI have the potential to be used as a nonpharmacological alternative for assessing myocardial oxygenation in patients with acute MI.
αvβ3-Specific Gold Nanoparticles for Fluorescence Imaging of Tumor Angiogenesis

This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for αvβ3-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance. Furthermore, the therapeutic properties of the AuNPs were evaluated in vitro on pUC19 DNA and on A431 cells concerning acute and long-term toxicity, indicating that these AuNPs could be useful as radiosensitizers in therapeutic concepts in the future.
Comparison of the anesthetic effects between 5 mg/kg of alfaxalone and 10 mg/kg of propofol administered intravenously in cats

To compare the anesthetic effects after intravenous administration of alfaxalone or propofol without premedication, either alfaxalone (5 mg/kg) or propofol (10 mg/kg) was administered intravenously over 120 sec in 6 cats. Each cat received the alternate treatment at least a 7-day interval. Anesthetic effects (tolerance of intubation, behavior changes and neurodepressive score) and physiological parameters were evaluated. Both treatments produced a rapid loss of consciousness, no apnea, and physiological parameters were maintained within clinically acceptable ranges apart from transient hypoxemia. The degree of hypoxemia was greater after the propofol treatment compared with the alfaxalone treatment. During the recovery period, more adverse events (ataxia, muscular tremors) were observed after the alfaxalone treatment compared with the propofol treatment.
A Predictive Model and Risk Factors for Case Fatality of COVID-19

This study aimed to create an individualized analysis model of the risk of intensive care unit (ICU) admission or death for coronavirus disease 2019 (COVID-19) patients as a tool for the rapid clinical management of hospitalized patients in order to achieve a resilience of medical resources. This is an observational, analytical, retrospective cohort study with longitudinal follow-up. Data were collected from the medical records of 3489 patients diagnosed with COVID-19 using RT-qPCR in the period of highest community transmission recorded in Europe to date: February–June 2020. The study was carried out in in two health areas of hospital care in the Madrid region: the central area of the Madrid capital (Hospitales de Madrid del Grupo HM Hospitales (CH-HM), n = 1931) and the metropolitan area of Madrid (Hospital Universitario Príncipe de Asturias (MH-HUPA) n = 1558). By using a regression model, we observed how the different patient variables had unequal importance. Among all the analyzed variables, basal oxygen saturation was found to have the highest relative importance with a value of 20.3%, followed by age (17.7%), lymphocyte/leukocyte ratio (14.4%), CRP value (12.5%), comorbidities (12.5%), and leukocyte count (8.9%). Three levels of risk of ICU/death were established: low-risk level (<5%), medium-risk level (5–20%), and high-risk level (>20%). At the high-risk level, 13% needed ICU admission, 29% died, and 37% had an ICU–death outcome. This predictive model allowed us to individualize the risk for worse outcome for hospitalized patients affected by COVID-19.
Effect of Different Austempering Heat Treatments on Corrosion Properties of High Silicon Steel

A novel high silicon austempered (AHS) steel has been studied in this work. The effect of different austenitizing temperatures, in full austenitic and biphasic regime, on the final microstructure was investigated. Specimens were austenitized at 780 °C, 830 °C, 850 °C and 900 °C for 30 min and held isothermally at 350 °C for 30 min. A second heat treatment route was performed which consisted of austenitizing at 900 °C for 30 min and austempering at 300 °C, 350 °C and 400 °C for 30 min. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) have been used to evaluate the microstructural evolution. These techniques revealed that the microstructures were composed of carbide-free bainite, ferrite, martensite and retained austenite (RA) in different volume fractions (Vγ). An aqueous borate buffer solution with 0.3 M H3BO3 and 0.075 M Na2B4O7∂10H2O (pH = 8.4) was used for corrosion tests in order to evaluate the influence of the different volume fractions of retained austenite on the corrosion properties of the specimens. The results showed that when increasing the austenitization temperatures, the volume fractions of retained austenite reached a maximum value at 850 °C, and decrease at higher temperatures. The corrosion properties were investigated after 30 min and 24 h immersion by means of potentiodynamic polarization (after 30 min) and electrochemical impedance spectroscopy (after both 30 min and 24 h) tests. The corrosion resistance of the samples increased with increases in the volume fraction of retained austenite due to lower amounts of residual stresses.