Miracle-dz/UniFAR-FTUs huggingface dataset:
Biosignature Analysis of Mars Soil Analogs from the Atacama Desert: Challenges and Implications for Future Missions to Mars.

The detection of biosignatures on Mars is of outstanding interest in the current field of Astrobiology and drives various fields of research, ranging from new sample collection strategies to the development of more sensitive detection techniques. Detailed analysis of the organic content in Mars analog materials collected from extreme environments on Earth improves the current understanding of biosignature preservation and detection under conditions similar to those of Mars. In this article, we examined the biological fingerprint of several locations in the Atacama Desert (Chile), which include different wet and dry, and intermediate to high elevation salt flats (also named salars). Liquid Chromatography and Multidimensional Gas Chromatography Mass Spectrometry measurement techniques were used for the detection and analysis of amino acids extracted from the salt crusts and sediments by using sophisticated extraction procedures. Illumina 16S amplicon sequencing was used for the identification of microbial communities associated with the different sample locations. Although amino acid load and organic carbon and nitrogen quantities were generally low, it was found that most of the samples harbored complex and versatile microbial communities, which were dominated by (extremely) halophilic microorganisms (most notably by species of the Archaeal family Halobacteriaceae). The dominance of salts (i.e., halites and sulfates) in the investigated samples leaves its mark on the composition of the microbial communities but does not appear to hinder the potential of life to flourish since it can clearly adapt to the higher concentrations. Although the Atacama Desert is one of the driest and harshest environments on Earth, it is shown that there are still sub-locations where life is able to maintain a foothold, and, as such, salt flats could be considered as interesting targets for future life exploration missions on Mars.
Unnecessary ankle series in emergency department - 20 years after Ottawa rules

Poster: "EuroSafe Imaging 2016 / ESI-0023 / Unnecessary ankle series in emergency department - 20 years after Ottawa rules" by: "G. Ivanac1, E. Divjak1, B. Brkljacic2; 1 Zagreb/HR, 2Medical School, University of Zagreb Zagreb/HR"
Biokinetics of Radiolabeled Monoclonal Antibody BC8: Differences in Biodistribution and Dosimetry Among Hematologic Malignancies

We reviewed 111In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the 111In-DOTA-BC8 (176–406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made. Bone marrow biopsies were obtained 14–24 h after infusion, and the percentage of administered activity was determined. Absorbed radiation doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (SD) of administered activity (52 patients), which cleared monoexponentially with a biologic half-time of 293 ± 157 h (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biologic half-time of 271 ± 185 h (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biologic half-time of 243 ± 144 h (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with a biologic half-time of 215 ± 107 h (43 patients) or longer (5 patients). Whole-body retention half-time averaged 198 ± 75 h. Splenic uptake was higher in the AML/MDS group than in the lymphoma group (P ≤ 0.05) or the multiple myeloma group (P ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed among the 3 malignancy groups. Average calculated radiation absorbed doses per unit of administered activity for a therapy infusion of 90Y-DOTA-BC8 were 0.35 ± 0.20 cGy/MBq for red marrow, 0.80 ± 0.24 cGy/MBq for liver, 3.0 ± 1.4 cGy/MBq for spleen, 0.055 ± 0.014 cGy/MBq for total body, 0.21 ± 0.15 cGy/MBq for osteogenic cells, and 0.17 ± 0.15 cGy/MBq for kidneys. Conclusion: 111In-DOTA-BC8 had a long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were in spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake in the leukemia/MDS group than in the lymphoma or multiple myeloma group.
Evaluation of fluticasone propionate/salmeterol for the treatment of COPD: a systematic review

ABSTRACT Introduction Recently, the generic formulation of FP/SAL FDC has been approved in COPD. Although FP/SAL FDC has been the first long-acting FDC approved in COPD, no systematic review assessed the effect of this combination for the treatment of COPD by considering specifically Phase IV studies. The aim of this review was to systematically assess the effect of FP/SAL FDC in COPD patients enrolled in Phase IV studies. Areas covered The question of this systematic review was to examine the evidence regarding the impact of FP/SAL FDC for the treatment of COPD by searching for Phase IV studies in the ClinicalTrials.gov database. Expert opinion Generic drugs represent an effective cost-saving step for health-care budgets in the treatment of COPD and should be used in agreement with current recommendations and prescription accuracy. FP/SAL FDC is recommended for the initiation therapy just in a small percentage of symptomatic patients that are at high risk of exacerbation with blood eosinophil counts ≥300 cells per μl. At follow-up, FP/SAL FDC can be escalated to triple ICS/LABA/LAMA combination or switched to LABA/LAMA combination by considering symptoms, exacerbations, lack of response to ICS, inappropriate original indication, and ICS-related adverse events such as pneumonia.
Macrophage lineages in heart valve development and disease.

Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from hematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that hematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications.
YTHDF2 destabilizes m6A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells

N6-methyladenosine (m6A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m6A-specific RNA binding proteins. Despite accumulating evidence that m6A plays an important role in modulating pluripotency, the influence of m6A reader proteins in pluripotency is less clear. Here, we report that YTHDF2, an m6A reader associated with mRNA degradation, is highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. Through RNA sequencing, we identified a group of m6A-modified transcripts associated with neural development that are directly regulated by YTDHF2. Depletion of YTHDF2 in iPSCs leads to stabilization of these transcripts, loss of pluripotency, and induction of neural-specific gene expression. Collectively, our results suggest YTHDF2 functions to restrain expression of neural-specific mRNAs in iPSCs and facilitate their rapid and coordinated up-regulation during neural induction. These effects are both achieved by destabilization of the targeted transcripts.
The Assessment and Relationship Between Quality of Life and Physical Activity Levels in Greek Breast Cancer Female Patients under Chemotherapy

A growing body of evidence suggests that physical activity (PA) can be a complementary intervention during breast cancer (BCa) treatment, contributing to the alleviation of the chemotherapy-related side-effects. The purpose of this study was to assess physical activity (PA) levels and quality of life (QoL) parameters of BCa patients undergoing chemotherapy and compare them with healthy controls. A total of 94 BCa female patients and 65 healthy women were recruited and self-reported QoL and PA levels. The results reveal that women suffering from BCa spent only 134 ± 469 metabolic equivalents (MET)/week in vigorous PAs compared with the healthy females who spent 985±1508 MET/week. Also, BCa patients were spending 4.62±2.58 h/day sitting, contrary to the 2.34±1.05 h/day of the controls. QoL was scored as 63.43±20.63 and 70.14±19.49 while physical functioning (PF) as 71.48±23.35 and 84.46±15.48 by BCa patients and healthy participants, respectively. Negative correlations were found between QoL and fatigue, PF and pain, and fatigue and dyspnea, while a positive correlation was found between QoL and PF. This study indicated that the BCa group accumulated many hours seated and refrained from vigorous Pas, preferring PAs of moderate intensity. Additionally, BCa patients’ levels of functioning and QoL were moderate to high; however, they were compromised by pain, dyspnea and fatigue.
Impact of cortical hemodynamic failure on both subsequent hemorrhagic stroke and effect of bypass surgery in hemorrhagic moyamoya disease: a supplementary analysis of the Japan Adult Moyamoya Trial.

OBJECTIVE Here, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease. METHODS Data from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup. RESULTS The hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07-27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04-0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22-11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056). CONCLUSIONS Hemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp).
Epidemiology of Coronavirus Disease in Gansu Province, China, 2020

To determine the epidemiology of coronavirus disease (COVID-19) in a remote region of China, far from Wuhan, we analyzed the epidemiology of COVID-19 in Gansu Province. From January 23 through February 3, 2020, a total of 35 (64.8%) of 54 reported cases were imported from COVID-19–epidemic areas. Characteristics that differed significantly during the first and second waves of illness in Gansu Province were mean patient age, occupation, having visited epidemic areas, and mode of transportation. Time from infection to illness onset for family clusters was shorter in Gansu Province than in Wuhan, consistent with shortened durations from onset to first medical visit or hospitalization. Spatial distribution pattern analysis indicated hot spots and spatial outliers in Gansu Province. As a result of adequate interventions, transmission of the COVID-19 virus in Gansu Province is decreasing.
Leisure-time physical activity volume, intensity, and duration from mid- to late-life in U.S. subpopulations by race and sex. The Atherosclerosis Risk In Communities (ARIC) Study

Mitigating age-related disease and disability presents challenges. Physical activity (PA) may be influential for prolonging health and functioning, warranting characterization of its patterns over the life course in population-based data. With the availability of up to three self-reported assessments of past year leisure-time PA (LTPA) over multiple decades in 15,036 participants (26% African American; 55% women; mean baseline age=54; median follow-up=23 years) from the Atherosclerosis Risk in Communities (ARIC) Study sampled from four U.S. communities, race-sex-stratified trajectories of average weekly intensity (metabolic equivalent of task (MET)), duration (hours), and energy expenditure or volume (MET-h) of LTPA were developed from age 45 to 90 using joint models to accommodate expected non-ignorable attrition. Declines in weekly LTPA intensity, duration, and volume from age 70 to 90 were observed in white women (2.9 to 1.2 MET; 2.5 to 0.6 h; 11.1 to 2.6 MET-h), white men (2.5 to 1.0 MET; 3.5 to 1.8 h; 15.5 to 6.4 MET-h), African American women (2.5 to 2.4 MET; 0.8 to 0.1 h; 6.7 to 6.0 MET-h), and African American men (2.3 to 1.4 MET; 1.5 to 0.6 h; 8.0 to 2.3 MET-h). These data reveal population-wide shifts towards less active lifestyles in older adulthood.
Therapeutic targeting of the DNA damage response in prostate cancer.

PURPOSE OF REVIEW The present article highlights the most common DNA repair gene mutations, using specific examples of individual genes or gene classes, and reviews the epidemiology and treatment implications for each one [with particular emphasis on poly-ADP-ribose polymerase (PARP) inhibition and PD-1 blockade]. RECENT FINDINGS Genetic and genomic testing have an increasingly important role in the oncology clinic. For patients with prostate cancer, germline genetic testing is now recommended for all men with high-risk and metastatic disease, and somatic multigene tumor testing is recommended for men with metastatic castration-resistant disease. The most common mutations that are present in men with advanced prostate cancer are in genes coordinating DNA repair and the DNA damage response. SUMMARY Although much of what is discussed currently remains investigational, it is clear that genomically-targeted treatments will become increasingly important for patients with prostate cancer in the near future and beyond.
Unilateral Stent Insertion With High-intensity Focused Ultrasound Ablation for Hilar Cholangiocarcinoma

Purpose: To evaluate the clinical effectiveness and long-term outcomes of unilateral stent insertion with high-intensity focused ultrasound ablation (HIFUA) in patients with hilar cholangiocarcinoma (HCCA). Materials and Methods: From March 2016 to June 2019, consecutive patients presenting with HCCA were treated with single stent insertion or stent with HIFUA. The long-term outcomes of the 2 groups were compared. Results: During the study period, 37 patients were included who underwent single stent insertion and 32 patients who underwent stent insertion with HIFUA. Eight (21.6%) patients in the single stent group and 6 (18.8%) in the combined group experienced stent dysfunction (P=0.767). Median stent patency in the single stent and combined groups was 169 and 225 days, respectively (P<0.001). All patients died because of tumor progression. The median poststent overall survival for patients in the single stent and combined groups were 178 and 246 days, respectively (P<0.001). Conclusion: HIFUA after unilateral stent insertion can prolong stent patency and survival of patients with inoperable HCCA.
Mitochondrial Respiration Correlates with Prognostic Markers in Chronic Lymphocytic Leukemia and Is Normalized by Ibrutinib Treatment

Mitochondrial bioenergetics profiling, a measure of oxygen consumption rates, correlates with prognostic markers and can be used to assess response to therapy in chronic lymphocytic leukemia (CLL) cells. In this study, we measured mitochondrial respiration rates in primary CLL cells using respirometry to evaluate mitochondrial function. We found significant increases in mitochondrial respiration rates in CLL versus control B lymphocytes. We also observed amongst CLL patients that advanced age, female sex, zeta-chain-associated protein of 70 kD (ZAP-70+), cluster of differentiation 38 (CD38+), and elevated β2-microglobulin (β2-M) predicted increased maximal respiration rates. ZAP-70+ CLL cells exhibited significantly higher bioenergetics than B lymphocytes or ZAP-70− CLL cells and were more sensitive to the uncoupler, carbonyl cyanide-p-trifluoro-methoxyphenylhydrazone (FCCP). Univariable and multivariable linear regression analysis demonstrated that ZAP-70+ predicted increased maximal respiration. ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton’s tyrosine kinase (BTK) inhibitor. Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL. Our data support evaluation of mitochondrial respiration as a preclinical tool for the response assessment of CLL cells.
Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.
New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a disease entity that comprises a heterogeneous group of biliary malignant neoplasms, with variable clinical presentation and severity. It may be classified according to its anatomical location and distinguished in intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), each subtype implying distinct epidemiology, biology, prognosis, and strategy for clinical management. Its incidence has increased globally over the past few decades, and its mortality rate remains high due to both its biological aggressiveness and resistance to medical therapy. Surgery is the only potentially curative treatment and is the standard approach for resectable CCA; however, more than half of the patients have locally advanced or metastatic disease at presentation. For patients with unresectable CCA, the available systemic therapies are of limited effectiveness. However, the advances of the comprehension of the complex molecular landscape of CCA and its tumor microenvironment could provide new keys to better understand the pathogenesis, the mechanisms of resistance and ultimately to identify promising new therapeutic targets. Recently, clinical trials targeting isocitrate dehydrogenase (IDH)-1 mutations and fibroblast growth factor receptor (FGFR)-2 fusions, as well as immunotherapy showed promising results. All these new and emerging therapeutic options are herein discussed.
Lung Function Decline in Farm and Nonfarm Rural Residents of Saskatchewan.

OBJECTIVE This study aims to assess the annual changes in lung function among farm and nonfarm adult residences in rural Saskatchewan, Canada. METHODS Data from the Saskatchewan Rural Health Study survey (2010 to 2014) among 724 adults were used. RESULTS For forced expiratory volume in 1 second (FEV1) measurements, estimates of annual decline (in milliliters) were highest in older age male (65+ years) (Mean, SD) (-42.63, 21.16); and among old heavy smokers (-57.79, 24.30). Estimates of annual decline in forced vital capacity (FVC) were highest in current smokers without the use of natural gas (-25.78, 14.78) and among old heavy smokers (-33.88, 20.28). Living on a farm is associated with decreased FEV1 and FVC, but not statistically significant by sex and age. CONCLUSIONS A complex mix of personal and contextual factors may affect these estimates.