Miracle-dz/UniFAR-FTUs huggingface dataset:
RNA Sequencing Analysis of the Broad-Host-Range Strain Sinorhizobium fredii NGR234 Identifies a Large Set of Genes Linked to Quorum Sensing-Dependent Regulation in the Background of a traI and ngrI Deletion Mutant

ABSTRACT The alphaproteobacterium Sinorhizobium fredii NGR234 has an exceptionally wide host range, as it forms nitrogen-fixing nodules with more legumes than any other known microsymbiont. Within its 6.9-Mbp genome, it encodes two N-acyl-homoserine-lactone synthase genes (i.e., traI and ngrI) involved in the biosynthesis of two distinct autoinducer I-type molecules. Here, we report on the construction of an NGR234-ΔtraI and an NGR234-ΔngrI mutant and their genome-wide transcriptome analysis. A high-resolution RNA sequencing (RNA-seq) analysis of early-stationary-phase cultures in the NGR234-ΔtraI background suggested that up to 316 genes were differentially expressed in the NGR234-ΔtraI mutant versus the parent strain. Similarly, in the background of NGR234-ΔngrI 466 differentially regulated genes were identified. Accordingly, a common set of 186 genes was regulated by the TraI/R and NgrI/R regulon. Coregulated genes included 42 flagellar biosynthesis genes and 22 genes linked to exopolysaccharide (EPS) biosynthesis. Among the genes and open reading frames (ORFs) that were differentially regulated in NGR234-ΔtraI were those linked to replication of the pNGR234a symbiotic plasmid and cytochrome c oxidases. Biotin and pyrroloquinoline quinone biosynthesis genes were differentially expressed in the NGR234-ΔngrI mutant as well as the entire cluster of 21 genes linked to assembly of the NGR234 type III secretion system (T3SS-II). Further, we also discovered that genes responsible for rhizopine catabolism in NGR234 were strongly repressed in the presence of high levels of N-acyl-homoserine-lactones. Together with nodulation assays, the RNA-seq-based findings suggested that quorum sensing (QS)-dependent gene regulation appears to be of higher relevance during nonsymbiotic growth rather than for life within root nodules.
A Random-sequential Mechanism for Nitrite Binding and Active Site Reduction in Copper-containing Nitrite Reductase*

The homotrimeric copper-containing nitrite reductase (NiR) contains one type-1 and one type-2 copper center per monomer. Electrons enter through the type-1 site and are shuttled to the type-2 site where nitrite is reduced to nitric oxide. To investigate the catalytic mechanism of NiR the effects of pH and nitrite on the turnover rate in the presence of three different electron donors at saturating concentrations were measured. The activity of NiR was also measured electrochemically by exploiting direct electron transfer to the enzyme immobilized on a graphite rotating disk electrode. In all cases, the steady-state kinetics fitted excellently to a random-sequential mechanism in which electron transfer from the type-1 to the type-2 site is rate-limiting. At low [NO–2] reduction of the type-2 site precedes nitrite binding, at high [NO–2] the reverse occurs. Below pH 6.5, the catalytic activity diminished at higher nitrite concentrations, in agreement with electron transfer being slower to the nitrite-bound type-2 site than to the water-bound type-2 site. Above pH 6.5, substrate activation is observed, in agreement with electron transfer to the nitrite-bound type-2 site being faster than electron transfer to the hydroxyl-bound type-2 site. To study the effect of slower electron transfer between the type-1 and type-2 site, NiR M150T was used. It has a type-1 site with a 125-mV higher midpoint potential and a 0.3-eV higher reorganization energy leading to an ∼50-fold slower intramolecular electron transfer to the type-2 site. The results confirm that NiR employs a random-sequential mechanism.
Relationship functioning and sexuality among people with multiple sclerosis

This study was concerned with how the sexuality and relationships of people with Multiple Sclerosis (MS) are different from those of people from the general population. Three‐hundred eighty‐one respondents (144 males, 237 females) with MS and 291 respondents (101 males, 190 females) from the general population participated in the study. Sexual satisfaction, sexual dysfunction, relationship satisfaction, and coping style were assessed among all respondents. Information was also obtained from people with MS regarding age of onset and diagnosis of symptoms, as well as severity of symptoms. Overall, males with MS experienced a higher frequency of sexual dysfunction than males from the general population, while females with MS only differed from females from the general population in their levels of masturbation and numbness of the genital area. Coping strategies and levels of cognitive functioning were important predictors of sexual satisfaction, sexual dysfunction, and relationship satisfaction for women with MS, but there were fewer coping or health‐related factors that predicted these variables among men with MS. The results of this study are discussed in terms of factors related to sexual satisfaction and positive interpersonal relationships. There is a need to conduct further research in this area so that professionals working with people with MS are informed on strategies to improve the sexuality and relationships of their clients' lives.
African American Women and Family Planning Services: Perceptions of Discrimination

ABSTRACT Objectives: The purpose of this study was to examine perceived race-based discrimination in obtaining family planning or contraceptive services among African American women in the U.S. Methods: We conducted a 30-minute telephone survey with a random sample of 500 African Americans (aged 15–44), which included questions about race-based discrimination when obtaining family planning services. The present analyses were limited to the 326 women who completed interviews. Results: The majority (79%) of women reported having seen a health care provider for family planning or birth control services. Of those, 67% reported race-based discrimination when obtaining such services. Half of the women reported more general experiences of discrimination when obtaining family planning services (e.g., poorer service), and 52% reported experiences that reflect stereotypes of African American women (e.g., doctor or nurse assumed they had multiple sexual partners). Most indicated that experiences of discrimination occurred infrequently. Generally, background characteristics were not significantly associated with perceived discrimination. However, in multivariate models, stronger Black identity, younger age, and lower income were associated with reports of discrimination. Conclusion: African American women may be vulnerable to prejudice within reproductive health care contexts, including family planning.
Comparative analysis of antibodies to xCT (Slc7a11): Forewarned is forearmed

The cystine/glutamate antiporter or system Xc− exchanges cystine for glutamate, thereby supporting intracellular glutathione synthesis and nonvesicular glutamate release. The role of system Xc− in neurological disorders can be dual and remains a matter of debate. One important reason for the contradictory findings that have been reported to date is the use of nonspecific anti‐xCT (the specific subunit of system Xc− ) antibodies. Often studies rely on the predicted molecular weight of 55.5 kDa to identify xCT on Western blots. However, using brain extracts from xCT knockout (xCT−/−) mice as negative controls, we show that xCT migrates as a 35‐kDa protein. Misinterpretation of immunoblots leads to incorrect assessment of antibody specificity and thereby to erroneous data interpretation. Here we have verified the specificity of most commonly used commercial and some in‐house‐developed anti‐xCT antibodies by comparing their immunoreactivity in brain tissue of xCT+/+ and xCT−/− mice by Western blotting and immunohistochemistry. The Western blot screening results demonstrate that antibody specificity not only differs between batches produced by immunizing different rabbits with the same antigen but also between bleedings of the same rabbit. Moreover, distinct immunohistochemical protocols have been tested for all the anti‐xCT antibodies that were specific on Western blots in order to obtain a specific immunolabeling. Only one of our in‐house‐developed antibodies could reveal specific xCT labeling and exclusively on acetone‐postfixed cryosections. Using this approach, we observed xCT protein expression throughout the mouse forebrain, including cortex, striatum, hippocampus, midbrain, thalamus, and amygdala, with greatest expression in regions facing the cerebrospinal fluid and meninges. J. Comp. Neurol. 524:1015–1032, 2016. © 2015 Wiley Periodicals, Inc.
CHILD AND MATERNAL ORAL HEALTHCARE: AN ASSESSMENT OF THE KNOWLEDGE OF NIGERIAN AND GHANAIAN NURSES.

OBJECTIVE To ascertain and compare knowledge of child and maternal oral healthcare amongst a group of Nurses and Midwives in Ghana and Nigeria. DESIGN A cross-sectional survey. SETTING Health institutions in Cape Coast, Ghana and Port Harcourt, Nigeria. SUBJECTS One hundred and sixty Nurses and Midwives (80 Ghanaians and 80 Nigerians). RESULTS They had an age range of 21-65 years and a mean age of 37.8 (SD ± 9.6) years. Majority of the Nurses in both countries indicated that women should brush their teeth with a toothbrush and toothpaste (92.1%), whilst the children should use salt and cotton wool twice daily. Although more of the Ghanaian Nurses (98.8%) considered routine dental visits to be important than the Nigerian population (80%), only 3.8% of the Ghanaian Nurses against 33.8% of the Nigerians indicated there was a connection between oral disease and delivery status. Opinions differed significantly as to the reason for the first dental visit with 65.4% of the Nigerian Nurses indicating this should be when the child has toothache whereas 51.9% of Ghanaian Nurses believed it is when the first tooth erupts. However, four to six years was the common choice for when self brushing should start in both countries. CONCLUSION The knowledge of this group of Nurses and Midwives on maternal and child oral healthcare was insufficient. The Ghanaian Nurses had a better knowledge of preventive dental care than their Nigerian counterparts.
Outcome prediction of diffuse large B-cell lymphomas associated with hepatitis C virus infection: a study on behalf of the Fondazione Italiana Linfomi

A specific prognostication score for hepatitis C virus-positive diffuse large B-cell lymphomas is not available. For this purpose, the Fondazione Italiana Linfomi (FIL, Italian Lymphoma Foundation) carried out a multicenter retrospective study on a large consecutive series of patients with hepatitis C virus-associated diffuse large B-cell lymphoma to evaluate the prognostic impact of clinical and virological features and to develop a specific prognostic score for this subset of patients. All prognostic evaluations were performed on 535 patients treated with an anthracycline-based induction regimen (with rituximab in 255 cases). Severe hepatotoxicity was observed in 14% of patients. The use of rituximab was not associated with increased rate of severe hepatotoxicity. Three-year overall survival and progression-free survival were 71% and 55%, respectively. At multivariate analysis, ECOG performance status of 2 or over, serum albumin below 3.5 g/dL and HCV-RNA viral load over 1000 KIU/mL retained prognostic significance. We combined these 3 factors in a new “HCV Prognostic Score” able to discriminate 3 risk categories with different overall and progression-free survival (low=0; intermediate=1; high-risk ≥2 factors; P<0.001). This score retained prognostic value in the subgroups of patients treated with and without rituximab (P<0.001). The new score performed better than the International Prognostic Index at multivariate analysis and Harrel C-statistic. With the use of three readily available factors (performance status, albumin level and HCV-RNA viral load), the new “HCV Prognostic Score” is able to identify 3 risk categories with different survival, and may be a useful tool to predict the outcome of hepatitis C virus-associated diffuse large B-cell lymphomas.
Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial.

PURPOSE Predicting efficacy and toxicity could potentially allow individualization of cancer therapy. We investigated putative pharmacogenetic markers of chemotherapy toxicity in a large randomized trial. PATIENTS, MATERIALS, AND METHODS Patients were randomly assigned to different sequences of chemotherapy for advanced colorectal cancer. First-line therapy was fluorouracil (FU), irinotecan/FU (IrFU) or oxaliplatin/FU (OxFU). Patients allocated first-line FU had planned second-line irinotecan alone, IrFU, or OxFU. The primary toxicity outcome measure was toxicity-induced delay or dose reduction; the secondary outcome was Common Terminology Criteria of Adverse Events grade >or= 3 toxicity. DNA was analyzed in 1,188 patients; 1,036 were assessable for the primary outcome, including 688 treated with FU, 270 with IrFU (first or second line), 280 with OxFU (first or second line), 184 with irinotecan alone, and 454 with any irinotecan-containing regimen. Ten polymorphisms were assessed: thymidylate synthase-enhancer region (TYMS-ER), thymidylate synthase 1494 (TYMS-1494), dihydropyrimidine dehydrogenase (DPYD), methylenetetrahydrofolate reductase (MTHFR), mutL homolog 1 (MLH1), UDP glucuronyltransferase (UGT1A1), ATP-binding cassette group B gene 1 (ABCB1), x-ray cross-complementing group 1 (XRCC1), glutathione-S-transferase P1 (GSTP1), and excision repair cross-complementing gene 2 (ERCC2). Results Using the primary outcome measure, no polymorphism was significantly associated (P < .01) with the toxicity of any regimen or with the difference in toxicity of IrFU or OxFU versus FU alone. Trends (of doubtful significance) were seen for associations of XRCC1, ERCC2, and GSTP1 with toxicity during irinotecan regimens: XRCC1, primary end point, any irinotecan-containing regimen (P = .045); ERCC2, secondary end point, irinotecan alone (P = .003); GSTP1, secondary end point; IrFU (P = .039); and irinotecan alone (P = .05). There was no evidence of association of UGT1A1*28 with irinotecan toxicity. CONCLUSION These results do not support the routine clinical use of the evaluated polymorphisms, including UGT1A1*28. Further investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan toxicity is warranted.
Identification and characteristics of imipenem-resistant Acinetobacter baumannii in surgical wards in a Chinese university hospital

Abstract The aim of this study was to investigate the prevalence and characteristics of imipenem-resistant Acinetobacter baumanni isolated from surgical wards in a university hospital, China. A total of 143 non-duplicate A. baumannii were isolated from 517 inpatients in surgery intensive care units (ICUs), burn wards, and general surgery wards. Of these, 102 isolates of A. baumannii (71.3%) were resistant to imipenem. Among imipenem-resistant isolates, all isolates were resistant to almost all antimicrobial agents except polymyxin E, all isolates were positive for blaOXA-23 and blaOXA-51 in addition to ISAba1, 52 (51%) were positive for blaOXA-58, 8 (7.8%) contained blaVIM-2, which co-harbored with blaOXA-58. Molecular typing revealed the presence of three clones among imipenem-resistant isolates. This study confirmed that A. baumannii strains harboring OXA or VIM type β-lactamases are widely distributed throughout the surgery wards. The data demonstrate that there was a high prevalence of imipenem-resistant A. baumannii infection in the region.
Computed tomography–based image-guided brachytherapy for cervical cancer: correlations between dose–volume parameters and clinical outcomes

Abstract This study evaluated the oncologic outcomes and complications of cervical cancer patients in terms of CT-based image-guided brachytherapy (IGBT) parameters. Of 68 cervical cancer patients treated with definitive radiotherapy/concurrent chemoradiotherapy, most received whole-pelvis external beam RT (EBRT) of 40 Gy in 20 fractions, pelvic EBRT with central shield of 10 Gy in 5 fractions, and CT-based IGBT of 18 Gy in 3 fractions prescribed to point A. Cumulative EBRT and IGBT doses were calculated as the total equivalent dose in 2 Gy fractions (EQD2). The median follow-up was 31 (3–52) months. The 2-year overall survival, local control, pelvic control, and disease-free survival rates of the 68 patients were 92%, 83%, 82% and 73%, respectively. The HR-CTV D90, length from the tandem axis to left/right margin of the HR-CTV (T-LR), and HR-CTV volume were significant IGBT parameters for predicting local/pelvic control. Patients who received an HR-CTV D90 of >60 Gy, compared with ≤60 Gy, had significantly better local/pelvic control. Furthermore, 70 Gy was a marginally significant HR-CTV D90 cut-off affecting local control. T-LR was an independent IGBT parameter predicting local/pelvic control on multivariate analysis. Three patients developed Grade 3 or higher treatment-related complications. The D2cm3 of organs at risk were not significant predictors of complications. Future challenges for further improving outcomes include additional interstitial needles for irregularly shaped HR-CTVs, and moderate dose escalation, especially for patients with poor tumor responses.
Dialytic Treatment for Septic Patients with Acute Kidney Injury

Background: Sepsis is the commonest precipitating factor for acute kidney injury in hospitalised patients, and similarly patients with acute kidney injury are predisposed to sepsis. Mortality remains high despite improvements in supportive care. Methods: Literature search of Medline and Web of Science. Results: Above a threshold dialytic dose of 20 ml/kg/h for continuous renal replacement therapy and a sessional Kt/V of 1.2 for intermittent dialysis, further increases in dose do not appear to impact on survival. Similarly, no treatment mode offers survival advantage, and renal support should be targeted to maintain electrolyte homeostasis and correct volume overload. Additional therapies designed to reduce the inflammatory milieu associated with sepsis have been studied, including increased permeability dialysers, plasma filtration and adsorption techniques, endotoxin filters, selective leucapheresis and bio-artificial renal devices. Antibiotic-coated catheters have been shown to reduce catheter-associated bacteraemia. Conclusions: Although no modality confers survival advantage, prevention of intratreatment hypotension may result in increased dialysis independence in the survivors, and as such treatments should be designed to minimise the risk of hypotension. As patients with acute kidney injury are at risk of sepsis, catheter-associated bacteraemia should be minimised by using antibiotic- or antiseptic-coated catheters, and hub colonisation reduced with appropriate catheter locks. Further trials of adjunct therapies designed to reduce the inflammatory milieu are required before these potential advances can be recommended for clinical practice.
Are Food Advanced Glycation End Products Toxic in Biological Systems?

Abstract: Model food advanced glycation end products (AGEs) were prepared as glycated casein (GC) and glycated soy protein (GS) by the reaction of casein or soy protein with glucose at 50°C, relative humidity 75% for seven days in a powder state. These browned proteins were used as materials for animal experiments. A mixture of 20% glycated proteins (GC:GS = 1:1) diet was fed to streptozotocin (STZ)‐diabetic rats for 11 weeks. The results showed that: (1) fructoselysine was observed in the hepatic portal veins, arteries, and femoral veins of rats fed with glycated proteins after 2 h of feeding; (2) blood sugar of glycated protein‐fed rats was lower than that of diabetic rats fed with intact protein, while HbA1C in blood and glucose in urine of both groups were similar; (3) lipid peroxidation status in serum, liver, and kidney of both groups was similar; (4) superoxide dismutase (SOD) and glutathione‐S‐transferase (GST) enzymatic activity in serum and liver of both groups were also similar; (5) there were no differences in degree of cataract formation and concentration of glucose, fructose, sorbitol, and lipid peroxide in the lenses of both groups. From the above results, it can be estimated that food AGEs are not toxic in biological systems, and reactive oxygen species increase in diabetic rats is not caused by glycated proteins but by other pathways.
Epidemiology & risk factors of scrub typhus in south India

Background & objectives: Scrub typhus is a major public health threat in South and Southeastern Asian countries including India. Understanding local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures against scrub typhus. The primary aim of this study was to identify specific epidemiological and geographical factors associated with an increased risk of developing scrub typhus in this region. Methods: We mapped 709 patients from Tamil Nadu, Andhra Pradesh and Telangana who were admitted to the Christian Medical College (CMC) Hospital, Vellore, Tamil Nadu, India, for the period 2006-2011, assessed seasonality using monthly counts of scrub typhus cases, and conducted a case-control study among a subset of patients residing in Vellore. Results: The geographic distribution of cases at CMC Hospital clusters around the Tamil Nadu-Andhra Pradesh border. However, distinct hotspots clearly exist distal to this area, near Madurai and the coast in Tamil Nadu, and in the Northeast of Andhra Pradesh. Seasonally, the highest numbers of cases were observed in the cooler months of the year, i.e. September to January. In the case-control analysis, cases were more likely to be agricultural laborers (OR 1.79, 95% CI 1.01 - 3.15), not wear a shirt at home (OR 4.23, 95% CI 1.12 - 16.3), live in houses adjacent to bushes or shrubs (OR 1.95, 95% CI 1.08 - 3.53), and live in a single room home (OR 1.75, 95% CI 1.02 - 3.01). On binary logistic regression, the first three of these variables were statistically significant. Interpretation & conclusions: With the growing number of cases detected in India, scrub typhus is fast emerging as a public health threat and further research to protect the population from this deadly infection is essential. Health education campaigns focusing on the agricultural workers of Southern India, especially during the cooler months of the year, can serve as an important public health measure to control infection.