Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced aquaporin-1 transcript expression in colorectal carcinoma is associated with promoter hypermethylation

ABSTRACT Aquaporin-1 (AQP1) is a homo-tetrameric transmembrane protein that facilitates rapid movement of water and ions across cell membranes. The clinical significance of AQP1 expression in colorectal carcinoma (CRC) is controversial. The aim of this study was to investigate the prognostic significance of AQP1 transcript expression and the association between expression and promoter methylation in normal colonic mucosa, CRC tissues and cell lines. Analysis of publicly available datasets from The Cancer Genome Atlas revealed that AQP1 expression was significantly decreased in CRC compared to normal mucosa (12.7 versus 33.3 respectively, P < 0.0001). However, expression increased with advanced disease, being significantly higher in stage IV (17.6) compared to either stage I (11.8, P = 0.0039) or II (10.9; P = 0.0023), and in patients with lymph node metastasis compared to those without (13.9 versus 11.3 respectively, P = 0.0023). Elevated expression was associated with decreased overall survival with univariate (Cox Proportional Hazard Ratio 1.60, 95% confidence interval 1.05–2.42, P = 0.028), but not multivariable analysis when considering the confounders stage and age. Analysis of HumanMethylation450 data demonstrated that AQP1 promoter methylation was significantly increased in CRC compared to normal mucosa. Analysis of CRC tissues and cell lines strongly suggested that methylation was associated with decreased expression. BRAFV600E mutation alone did not explain the increase in methylation. In conclusion, AQP1 transcript expression was decreased in CRC compared to normal mucosa, and this was associated with AQP1 promoter hypermethylation. AQP1 transcript expression increased with advanced disease but was not an independent prognostic indicator.
Understanding Economic Abuse Through an Intersectional Lens: Financial Abuse, Control, and Exploitation of Women’s Productive and Reproductive Labor

Financial abuse refers to men’s control over money, assets, and women’s education or paid work. As a corrective to existing undertheorization of men’s (and their family’s) abuse of and control over women’s unpaid (domestic) labor, this article proposes a new conceptualization of economic abuse. Drawing upon life-history interviews with 41 South Asian women from the United Kingdom and India, this article explores control and abuse in relation to financial resources and women’s paid work as well as unpaid work. It utilizes an intersectional perspective to explore how gender, migration status, race/ethnicity, and class can improve understanding of women’s experiences as a continuum of economic abuse.
New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements

αβ CD8+, γδ, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8+ T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for γδ and NK cell populations. Moreover, the distinction between the aging of these populations due to cellular differentiation or due to the chronological age of the donor has not been formally considered. In this study, we performed systematic measurements of telomere length and telomerase activity in human αβ CD8+, γδ, and NK lymphocytes based on subset division and across age to address these points and better understand the dichotomy between differentiation and temporal aging. This approach enables us to position phenotypically distinct γδ or NK subsets along a putative pathway of differentiation, such as for CD8+ T cells. Moreover, our data show that both cellular differentiation and donor aging have profound but independent effects on telomere length and telomerase activity of lymphocyte subpopulations, implying distinct mechanisms and consequences on the immune system.
New Generation mechanical circulatory support during high-risk PCI: a cross sectional analysis.

AIMS To establish the value of new generation mechanical circulatory support (MCS) devices such as heartmate PHP (Abott), Impella CP (Abiomed) and PulseCath iVAC2L (Terumo). METHODS AND RESULTS we retrospectively analyzed all consecutive elective high-risk PCI procedures performed in the Erasmus Medical Center (2011-2018) thereby comparing MCS protected and unprotected patients. The primary end-point was a composite of procedure related adverse events including death (<24 hours), cardiac arrest, need for vasopressors, rescue MCS, endotracheal intubation and limb ischemia with need for surgery. Secondary end-points included 30day survival. A total of 198 elective high-risk PCI patients were included (69 (35%) MCS-protected, 129 (65%) MCS unprotected). When compared with unprotected patients, MCS protected patients had a significant worse LVEF (25±10vs33±8%,p<0.01) and higher syntax-I score (33±11vs24±8,p<0.01). The primary end-point occurred in 26 (20%) of the unprotected patients and in 6 (9%) of the MCS protected patients (OR 0.38,95% CI 0.15-0.97,p=0.04). Patients under 75 years of age, with a syntax I score above 32 and with a left ventricular ejection fraction below 30% showed most potential benefit from MCS. Survival during the first 24hours after the procedure and at 30days was significantly higher in MCS protected patients (100%vs95%,p=0.04 at 24hours and 98%vs87%,OR 10.32, 95%CI (1.34:79.31), p=0.006 at 30days). CONCLUSIONS In a consecutive real-world cohort of high-risk PCI patients, protection with new generation MCS resulted in better procedural outcomes despite worse EF and more complex coronary artery disease at baseline. Larger prospective studies need to confirm these findings.
Osteogenesis inducers promote distinct biological responses in aortic and mitral valve interstitial cells

Both aortic and mitral valves calcify in pathological conditions; however, the prevalence of aortic valve calcification is high whereas mitral valve leaflet calcification is somewhat rare. Patterns of valvular calcification may differ due to valvular architecture, but little is known to that effect. In this study, we investigated the intrinsic osteogenic differentiation potential of aortic versus mitral valve interstitial cells provided minimal differentiation conditions. For the assessment of calcification at the cellular level, we used classic inducers of osteogenesis in stem cells: β‐glycerophosphate (β‐Gly), dexamethasone (Dex), and ascorbate (Asc). In addition to proteomic analyses, osteogenic markers and calcium precipitates were evaluated across treatments of aortic and mitral valve cells. The combination of β‐Gly, Asc, and Dex induced aortic valve interstitial cells to synthesize extracellular matrix, overexpress osteoblastic markers, and deposit calcium. However, no strong evidence showed the calcification of mitral valve interstitial cells. Mitral cells mainly responded to Asc and Dex by cell activation. These findings provide a deeper understanding of the physiological properties of aortic and mitral valves and tendencies for calcific changes within each valve type, contributing to the development of future therapeutics for heart valve diseases.
Clinical Impact of Tumor DNA Repair Expression and T-cell Infiltration in Breast Cancers

This study provides clinical evidence that the interplay between DNA repair, CD8+ T cells, and expression of PD-L1 and PD-1 can promote aggressive tumor phenotypes. XRCC1-directed personalization of immune checkpoint inhibitor therapy may be feasible in breast cancer. Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1,269 breast cancers and validated our findings in an independent estrogen receptor–negative (ER−) cohort (n = 279). Patients with tumors that expressed low XRCC1, low ATM, and low BRCA1 were not only associated with high numbers of CD8+ tumor-infiltrating lymphocytes, but were also linked to higher grades, high proliferation indexes, presence of dedifferentiated cells, ER− cells, and poor survival (all P ≤ 0.01). PD-1+ or PD-L1+ breast cancers with low XRCC1 were also linked to an aggressive phenotype that was high grade, had high proliferation indexes, contained dedifferentiated cells and ER− (all with P values ≤ 0.01), and poor survival (P = 0.00021 and P = 0.00022, for PD-1+ and PD-L1+ cancers, respectively) including in an independent ER− validation cohort (P = 0.007 and P = 0.047, respectively). We conclude that the interplay between DNA repair, CD8, PD-L1, and PD-1 can promote aggressive tumor phenotypes. XRCC1-directed personalization of immune checkpoint inhibitor therapy may be feasible and warrants further investigation in breast cancer. Cancer Immunol Res; 5(4); 292–9. ©2017 AACR.
Factors Predictive of Outcomes after Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colon and Appendiceal Carcinomatosis: A Single-Institution Experience

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), although considered an acceptable treatment option in the management of selected patients with colon and appendiceal peritoneal carcinomatosis (PC), concerns about morbidity have limited its acceptance. Our objective was to evaluate the short- and long-term outcomes of CRS/HIPEC for appendix and colon PC performed at our institution and to elucidate factors predictive of patient outcomes. All patients who underwent CRS/HIPEC for appendix or colon PC from 2011 to 2017 were identified from our institution's prospective database. Postoperative outcomes, overall survival, and recurrence-free survival were assessed. Of 125 patients who underwent CRS/HIPEC during the study period, 45 patients were eligible (appendix n = 26; colon n = 19). The median postoperative length of stay was nine days (5–28 days). Grade III/IV complications occurred in 4/45 (8.8%) patients. There were no postoperative mortalities. Median DFS and overall survival have not yet been reached, in both the colon and appendix groups. As of the study conclusion date, 37/45 (82.2%) patients were alive with or without disease. Lymph node status was predictive of recurrence in appendix PC. In our experience, CRS/HIPEC can be safely performed with acceptable short- and long-term outcomes. Lymph node status is an important predictor of recurrence.
Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults

Hemoglobin concentration varies substantially in humans. In this perspective article, Dr. Patel examines the many factors responsible for this variability, including genetic ones. The large interindividual variation in hemoglobin concentration has important implications for the diagnosis and treatment of anemia, particularly in older adults. See related paper on page 1372.
Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction])

Background: Contemporary ST-segment–elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging–assessed infarct size. Secondary end points included cardiac magnetic resonance–determined myocardial salvage and creatine kinase kinetics. Results: Of 112 randomized patients with ST-segment–elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance–assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P=0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37–79) compared with placebo (27%; interquartile range, 14–42; P<0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (P=0.08). Conclusions: High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr. org.au/. Unique identifier: 12610000280000.
Tunable Synthesis of Mesoporous Carbons from Fe3O(BDC)3 for Chloramphenicol Antibiotic Remediation

Chloramphenicol (CAP) is commonly employed in veterinary clinics, but illegal and uncontrollable consumption can result in its potential contamination in environmental soil, and aquatic matrix, and thereby, regenerating microbial resistance, and antibiotic-resistant genes. Adsorption by efficient, and recyclable adsorbents such as mesoporous carbons (MPCs) is commonly regarded as a “green and sustainable” approach. Herein, the MPCs were facilely synthesized via the pyrolysis of the metal–organic framework Fe3O(BDC)3 with calcination temperatures (x °C) between 600 and 900 °C under nitrogen atmosphere. The characterization results pointed out mesoporous carbon matrix (MPC700) coating zero-valent iron particles with high surface area (~225 m2/g). Also, significant investigations including fabrication condition, CAP concentration, effect of pH, dosage, and ionic strength on the absorptive removal of CAP were systematically studied. The optimal conditions consisted of pH = 6, concentration 10 mg/L and dose 0.5 g/L for the highest chloramphenicol removal efficiency at nearly 100% after 4 h. Furthermore, the nonlinear kinetic and isotherm adsorption studies revealed the monolayer adsorption behavior of CAP onto MPC700 and Fe3O(BDC)3 materials via chemisorption, while the thermodynamic studies implied that the adsorption of CAP was a spontaneous process. Finally, adsorption mechanism including H-bonding, electrostatic attraction, π–π interaction, and metal–bridging interaction was proposed to elucidate how chloramphenicol molecules were adsorbed on the surface of materials. With excellent maximum adsorption capacity (96.3 mg/g), high stability, and good recyclability (4 cycles), the MPC700 nanocomposite could be utilized as a promising alternative for decontamination of chloramphenicol antibiotic from wastewater.
Capturing and Explaining Sensory Differences among Organically Grown Vegetable-Soybean Varieties Grown in Northern California.

Vegetable soybean (VS), known as edamame, is appreciated for its robust flavor and exceptional nutrient content. Although the United States is one of the world's leading producers of soy, only a fraction is harvested as edamame. Research involving varietal differences is very limited, particularly among U.S. consumers. Sensory attributes of three VS varieties grown in Northern California (with organic methods) were assessed: Giant Midori (GM), ButterBean (BB), and Kuroshinja (KU). Participants (n = 74) rated four characteristics: flavor, texture, appearance, and overall liking on unlabeled, 11-point hedonic scales and were asked if they would purchase the variety. A small portion of these participants would again evaluate the varieties, using free choice profiling (FCP) methodology. After these evaluations, texture analyzer, colorimeter, and high-performance liquid chromatography (free amino acids, sugars, and isoflavones) testing were performed. Among tested varieties, distinct differences in quality were found, with GM preferred first, followed by KU, and BB. GM was significantly harder, a more intense green, had more free sugars and isoflavones and fewer free amino acids, whereas KU and BB trended to be the opposite. Analyzing FCP data with a General Procrustes Analysis, varieties were separated in different factors for flavor and texture, but not appearance. Although repeated, and larger trials are needed, our study signifies that consumers are able to detect differences among VS varieties. Further research may influence producers to grow the variety likely to be most profitable and marketable.
Age‐stratified anti‐HAV positivity in Pune, India after two decades: Has voluntary vaccination impacted overall exposure to HAV?

The degree of transmission of hepatitis A virus (HAV) is inversely proportional to the socioeconomic status of a community. Serosurveys conducted at Pune, India during 1982‐98 documented significant reduction in HAV exposure of paediatric, higher socioeconomic status (HSS) population. Anti‐HAV positivity (ELISA) in age‐stratified Pune population representing HSS and lower middle socioeconomic status (LMSS) (n = 1065) and infants till the age of 15 months (n = 690) was determined in 2017. Anti‐HAV positivity in the LMSS population decreased significantly in 2017 while an increase was seen in the HSS category. The surprising rise in anti‐HAV positivity in the HSS population reflected vaccine‐ and infection‐induced antibodies while only infection‐induced antibodies were present in the LMSS category. Lowest antibody prevalence in infants was at 12 months, the recommended age for hepatitis A vaccination. Improved hygiene and selective immunization practices impacted HAV exposure of the LMSS population. The data emphasize the need for hepatitis A vaccination irrespective of socioeconomic status.
Giving callers the option to bypass the telephone waiting line in out-of-hours services: a comparative intervention study

Abstract Objective: Acute out-of-hours (OOH) healthcare is challenged by potentially long waiting time for callers in acute need of medical aid. OOH callers must usually wait in line, even when contacting for highly urgent or life-threatening conditions. We tested an emergency access button (EAB), which allowed OOH callers to bypass the waiting line if they perceived their health problem as severe. We aimed to investigate EAB use and patient characteristics associated with this use. Design: Comparative intervention study. Setting: OOH services in two major Danish healthcare regions. Intervention: Giving callers the option to bypass the telephone waiting line by introducing an EAB. Participants: OOH service callers contacting during end of October to mid-December 2017. Main outcome measures: Proportions of EAB use, waiting time and background information on participants in two settings differing on organisation structure, waiting time and triage personnel. Results: In total, 97,791 out of 158,784 callers (61.6%) chose to participate. The EAB was used 2905 times out of 97,791 (2.97%, 95%CI 2.86; 3.08). Patient characteristics associated with increased EAB use were male gender, higher age, low education, being retired, and increasing announced estimated waiting time. In one region, immigrants used the EAB more often than native Danish callers. Conclusion: Only about 3% of all callers chose to bypass the waiting line in the OOH service when given the option. This study suggests that the EAB could serve as a new and simple tool to reduce the waiting time for severely ill patients in an OOH service telephone triage setting. Key Points Acute out-of-hours healthcare is challenged by overcrowding and increasing demand for services. This study shows that only approximately 3% of callers chose to bypass the telephone waiting queue when given the opportunity through an emergency access button. An emergency access button may serve as a new tool to help reduce the triage waiting time for severely ill patients in out-of-hours medical facilities.
The genetic population structure and temporal genetic stability of gilthead sea bream Sparus aurata populations in the Aegean and Ionian Seas, using microsatellite DNA markers.

We examined 662 gilthead sea bream Sparus aurata from wild samples of the species in the Aegean and Ionian Seas, using 20 EST-linked microsatellite markers, in three multiplex panels, as well as seven anonymous loci. Most of the markers were revealed to be highly polymorphic. We found low genetic differentiation between the sampling stations/areas with total FST 0.002 (P < 0.05). Based on comparison of five temporal samples, our results indicate genetic data consistency over time for all tested samples, pointing to stable populations, despite reported repeated escape events. Our results confirm the genetic population structure previously observed in these specific areas, using by far more markers than in previous studies in both coding and non-coding DNA loci. The limited genetic structure and the temporal genetic stability indicate neither major genetic differentiation of local populations by geographic isolation nor influence from anthropogenic factors. These results provide a baseline for future reference in any management programme of both wild and farmed population of S. aurata as well as of other aquaculture species with a potential introgression among farmed and wild populations.
Karyopherin Msn5 is involved in a novel mechanism controlling the cellular level of cell cycle regulators Cln2 and Swi5

ABSTRACT The yeast β-karyopherin Msn5 controls the SBF cell-cycle transcription factor, responsible for the periodic expression of CLN2 cyclin gene at G1/S, and the nuclear export of Cln2 protein. Here we show that Msn5 regulates Cln2 by an additional mechanism. Inactivation of Msn5 causes a severe reduction in the cellular content of Cln2. This occurs by a post-transcriptional mechanism, since CLN2 mRNA level is not importantly affected in asynchronous cultures. Cln2 stability is not significantly altered in msn5 cells and inactivation of Msn5 causes a reduction in protein level even when Cln2 is stabilized. Therefore, the reduced amount of Cln2 in msn5 cells is mainly due not to a higher rate of protein degradation but to a defect in Cln2 synthesis. In fact, analysis of polysome profiles indicated that Msn5 inactivation causes a shift of CLN2 and SWI5 mRNAs from heavy-polysomal to light-polysomal and non-polysomal fractions, supporting a defect in Cln2 and Swi5 protein synthesis in the msn5 mutant. The analysis of truncated versions of Cln2 and of chimeric cyclins combining distinct domains from Cln2 and the related Cln1 cyclin identified an internal region in Cln2 from 181 to 225 residues that when fused to GFP is able to confer Msn5-dependent regulation of protein cellular content. Finally, we showed that a high level of Cln2 is toxic in the absence of Msn5. In summary, we described that Msn5 is required for the proper protein synthesis of specific proteins, introducing a new level of control of cell cycle regulators. Graphical Abstract