Takshan/R1 huggingface dataset:
A randomized trial of phenylephrine infusion versus bolus dosing for nausea and vomiting during Cesarean delivery in obese women.

Une étude randomisée comparant une perfusion versus un bolus de phényléphrine chez des femmes obèses pour traiter les nausées et vomissements pendant un accouchement par césarienne. PURPOSE: Hypotension is common after spinal anesthesia for Cesarean delivery. It is associated with nausea, vomiting, and fetal acidosis. Previous research on phenylephrine excluded obese subjects. We compared the incidence of intraoperative nausea and vomiting (IONV) in obese patients who received a prophylactic phenylephrine infusion vs those who received bolus dosing for the treatment of spinal-induced hypotension. METHODS: In this multicentre, double-blinded randomized controlled trial, 160 obese women undergoing elective Cesarean delivery under spinal anesthesia were randomized to receive a prophylactic phenylephrine infusion initiated at 50 μg·min-1 (and titrated according to a predefined algorithm) or 100 μg phenylephrine boluses to treat hypotension. Maternal systolic blood pressure was maintained within 20% of baseline. The primary study outcome was the incidence of IONV. RESULTS: Intraoperative nausea and vomiting were significantly reduced in the infusion group compared to the bolus group (46% vs 75%, respectively; relative risk [RR], 0.61; 95% confidence interval [CI], 0.47 to 0.80; P < 0.001). This was associated with significantly reduced need for intraoperative rescue antiemetics (26% vs 42%, respectively; RR, 0.62; 95% CI, 0.40 to 0.97; P = 0.04), but no difference in the incidence of vomiting. Postoperative vomiting at two hours was reduced in the infusion group (11% vs 25%; RR, 0.44; 95% CI, 0.21 to 0.90; P = 0.02);however, there were no differences in the incidence or severity of postoperative nausea, need for rescue antiemetics at two hours and 24 hr, or the incidence of postoperative vomiting at 24 hr. CONCLUSION: In obese women undergoing Cesarean delivery with spinal anesthesia, prophylactic phenylephrine infusion was associated with less intraoperative nausea, less need for rescue antiemetics, and reduced early postoperative vomiting. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01481740). Registered 22 July 2011.
Fatal cerebral hemorrhage in a tetraplegic patient due to autonomic dysreflexia triggered by delay in emptying urinary bladder after unsuccessful intermittent catheterization by carer: lessons learned.

Introduction: Over-distension of urinary bladder in a high spinal cord injury patient is a triggering factor for autonomic dysreflexia. Removing triggering factors is vital to prevent autonomic dysreflexia. Case presentation: A 36-year-old tetraplegic patient, who was managed by intermittent catheterizations performed by caregivers, developed recurrent autonomic dysreflexia during a week due to: 1) carers not performing intermittent catheterizations every night; 2) infrequent catheterizations during the day, leading to distension of urinary bladder. A day before his demise, carer attempted routine catheterization; but was unable to insert the catheter; blood pressure rose to 192/109 mmHg. Nifedipine 10 mg was administered. Thirty minutes later, blood pressure was 181/113 mmHg; second dose of Nifedipine was not given. Forty minutes elapsed before a senior carer came and catheterized successfully. Meanwhile, patient developed pounding headache; became drowsy; was talking incoherently. Four and half hours after unsuccessful catheterization, carers contacted emergency services and the patient was taken to Accident and Emergency; CT of head revealed very large acute intracranial hemorrhage in the right frontal and parietal lobes. The patient expired a day later. The Coroner's verdict: "Patient died of massive intracranial hemorrhage caused by autonomic dysreflexia, a known complication of high spinal cord injury. Emergency protocols to manage autonomic dysreflexia were not followed in the days leading up to his death." Conclusion: Failed urethral catheterization is a potentially life-threatening emergency; every patient should have a care plan explicitly describing what should be done when catheterization is not successful. Preventive measures rather than episodic treatment of autonomic dysreflexia should be the guiding principle.
Histone Deacetylase Inhibition Restores Expression of Hypoxia-Inducible Protein NDRG1 in Pancreatic Cancer.

OBJECTIVES: N-myc downstream-regulated gene-1 (NDRG1) is a hypoxia-inducible and differentiation-related protein and candidate biomarker in pancreatic cancer. As NDRG1 expression is lost in high-grade tumors, the effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) were examined in human pancreatic cancer cell lines representing different tumor grades. METHODS: PANC-1 (poorly differentiated) and Capan-1 (moderately to well-differentiated) cells were treated with TSA. Effects were assessed in vitro by microscopic analysis, colorimetric assays, cell counts, real-time polymerase chain reaction, and Western blotting. RESULTS: Treatment of PANC-1 cells over 4 days with 0.5 μM TSA restored cellular differentiation, inhibited proliferation, and enhanced p21 protein expression. Trichostatin A upregulated NDRG1 mRNA and protein levels under normoxia from day 1 and by 6-fold by day 4 (P < 0.01 at all time points). After 24 hours under hypoxia, NDRG1 expression was further increased in differentiated cells (P < 0.01). Favorable changes were identified in the expression of other hypoxia-regulated genes. CONCLUSIONS: Histone deacetylase inhibitors offer a potential novel epidrug approach for pancreatic cancer by reversing the undifferentiated phenotype and allowing patients to overcome resistance and better respond to conventional cytotoxic treatments.
Systematic Review of Validity Assessments of Framingham Risk Score Results in Health Economic Modelling of Lipid-Modifying Therapies in Europe.

BACKGROUND: The Framingham Risk Score is used both in the clinical setting and in health economic analyses to predict the risk for future coronary heart disease events. Based on an American population, the Framingham Risk Score has been criticised for potential overestimation of risk in European populations. OBJECTIVE: We investigated whether the use of the Framingham Risk Score actually was validated in health economic studies that modelled the effects of lipid-lowering treatment with statins on coronary heart disease events in European populations. METHODS: In this systematic literature review of all relevant published studies in English (literature searched September 2016 in PubMed, EMBASE and SCOPUS), 99 studies were identified and 22 were screened in full text, 18 of which were included. Key data were extracted and synthesised narratively. RESULTS: The only type of validation identified was a comparison against coronary heart disease risk data from one primary preventive and one secondary preventive clinical investigation, and from observational population data in one study. Taken together, those three studies reported an overall satisfactory accuracy in the results obtained by Framingham Risk Score predictions, but the Framingham Risk Score tended to underestimate non-fatal myocardial infarctions. In five studies, potential issues in applying the Framingham Risk Score on a European population were not addressed. CONCLUSION: Further studies are needed to ascertain that the Framingham Risk Score can accurately predict cardiovascular outcome in health economic modelling studies on lipid-lowering therapy in European populations. Future modelling studies using the Framingham Risk Score would benefit from validating the results against other data.
Effectiveness of Tachosil(®) in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis.

PURPOSE: Postoperative pancreatic fistula (POPF) is a frequent and clinically relevant problem after distal pancreatectomy. A variety of methods have been tested in the attempt to prevent POPF, most of them without convincing results. METHODS: A systematic literature search was conducted in PubMed, Embase and the Cochrane Library to identify clinical studies comparing pancreatic stump closure with the addition of Tachosil(®) to conventional stump closure. The identified studies were critically appraised, and meta-analyses were performed using a random-effects model. Dichotomous data were pooled using odds ratios, and weighted mean differences were calculated for continuous outcomes, together with the corresponding 95 % confidence intervals. RESULTS: Four studies (two randomised controlled trials and two retrospective clinical studies) reporting data from 738 patients were included in the meta-analysis. Overall POPF, clinically-relevant POPF, mortality, reoperations, intraoperative blood loss and length of hospital stay did not differ significantly between conventional closure and additional covering of the pancreatic stump with Tachosil(®). A sensitivity analysis of only randomised controlled trials confirmed the results. CONCLUSIONS: The application of Tachosil(®) to the pancreatic stump after distal pancreatectomy is a safe procedure but provides no relevant benefit in terms of POPF, mortality, reoperation rate, blood loss or length of hospital stay. Future research should concentrate on novel methods of pancreatic stump closure to prevent POPF after distal pancreatectomy.
MYC amplification in subtypes of breast cancers in African American women.

BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling. RESULTS: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4). CONCLUSIONS: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.
Competition between humic acid and carbonates for rare earth elements complexation.

The competitive binding of rare earth elements (REE) to humic acid (HA) and carbonates was studied experimentally at various pH and alkalinity values by combining ultrafiltration and inductively coupled plasma mass spectrometry techniques. The results show that the REE species occur as binary humate or carbonate complexes but not as ternary REE-carbonate-humate as previously proposed. The results also reveal the strong pH and alkalinity dependence of the competition as well as the existence of a systematic fractionation across the REE series. Specifically, carbonate complexation is at a maximum at pH 10 and increase with increasing alkalinity and with the atomic number of the REE (LuCO(3)>LaCO(3)). Modeling of the data using Model VI and recently published stability constants for complexation of REE by humic acid well reproduced the experimental data, confirming the ability of Model VI to accurately determine REE speciation in natural waters. This modeling also confirms the reliability of recently published stability constants. This work shed more light not only on the competition between carbonates and HA for REE complexation but also on the reliability of WHAM 6 and Model VI for calculating the speciation of REE with organic matter in alkaline organic-rich water.
An analysis of dietary fiber and fecal fiber components including pH in rural Africans with colorectal cancer.

Background/Aims: Colorectal cancer (CRC) is now a major public health problem with heavy morbidity and mortality in rural Africans despite the lingering dietary fiber-rich foodstuffs consumption. Studies have shown that increased intake of dietary fiber which contribute to low fecal pH and also influences the activity of intestinal microbiota, is associated with a lowered risk for CRC. However, whether or not the apparent high dietary fiber consumption by Africans do not longer protects against CRC risk is unknown. This study evaluated dietary fiber intake, fecal fiber components and pH levels in CRC patients. Methods: Thirty-five subjects (CRC=21, control=14), mean age 45 years were recruited for the study. A truncated food frequency questionnaire and modified Goering and Van Soest procedures were used. Results: We found that all subjects consumed variety of dietary fiber-rich foodstuffs. There is slight preponderance in consumption of dietary fiber by the control group than the CRC patients. We also found a significant difference in the mean fecal neutral detergent fiber, acid detergent fiber, hemicellulose, cellulose and lignin contents from the CRC patients compared to the controls (P<0.05). The CRC patients had significantly more fecal pH level than the matched apparently healthy controls (P=0.017). Conclusions: The identified differences in the fecal fiber components and stool pH levels between the 2 groups may relate to CRC incidence and mortality in rural Africans. There is crucial need for more hypothesis-driven research with adequate funding on the cumulative preventive role of dietary fiber-rich foodstuffs against colorectal cancer in rural Africans "today."
Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity-a pilot study.

Background: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2) and normal weight (NW, BMI < 25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. Results: Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. Conclusions: Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
Racial and cultural minority experiences and perceptions of health care provision in a mid-western region.

BACKGROUND: Disparities across a number of health indicators between the general population and particular racial and cultural minority groups including African Americans, Native Americans and Latino/a Americans have been well documented. Some evidence suggests that particular groups may receive poorer standards of care due to biased beliefs or attitudes held by health professionals. Less research has been conducted in specifically non-urban areas with smaller minority populations. METHODS: This study explored the self-reported health care experiences for 117 racial and cultural minority Americans residing in a Mid-Western jurisdiction. Prior health care experiences (including perceived discrimination), attitudes towards cultural competence and satisfaction with health care interactions were ascertained and compared across for four sub-groups (African-American, Native American, Latino/a American, Asian American). A series of multiple regression models then explored relationships between a concert of independent variables (cultural strength, prior experiences of discrimination, education level) and health care service preferences and outcomes. RESULTS: Overall, racial/cultural minority groups (African Americans, Native Americans, Latino/a Americans, and Asian Americans) reported general satisfaction with current healthcare providers, low levels of both health care provider racism and poor treatment, high levels of cultural strength and good access to health care services. Native American participants however, reported more frequent episodes of poor treatment compared to other groups. Incidentally, poor treatment predicted lower levels of treatment satisfaction and racist experiences predicted being afraid of attending conventional health care services. Cultural strength predicted a preference for consulting a health care professional from the same cultural background. CONCLUSIONS: This study provided a rare insight into minority health care expectations and experiences in a region with comparatively lower proportions of racial and cultural minorities. Additionally, the study explored the impact of cultural strength on health care interactions and outcomes. While the bulk of the sample reported satisfaction with treatment, the notable minority of participants reporting poor treatment is still of some concern. Cultural strength did not appear to impact health care behaviours although it predicted a desire for cultural matching. Implications for culturally competent health care provision are discussed within.
Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study.

Background: The ongoing extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs), medical and surgical wards between 2009 and 2013. Methods: This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011. Results: Over the study period, carbapenem consumption in ICUs (n = 85), medical (n = 227) and surgical wards (n = 181) was equal to 73.4, 6.2 and 5.4 defined daily doses per 1000 patient-days, respectively. Release of guidelines was followed by a significant decrease in carbapenem use within ICUs and medical wards, and a slowdown in use within surgical wards. The following factors were independently associated with a higher probability of reducing carbapenem use: location in Eastern France, higher initial carbapenem prescribing profile and reductions in consumption of fluoroquinolones, glycopeptides and piperacillin/tazobactam. In parallel, factors independently associated with a lower probability of reducing carbapenem use were ICUs, ward size increase, wards of cancer centres, higher initial third-generation cephalosporin (3GC) prescribing profile and location in high-risk regions for ESBL-PE. Conclusions: Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.
Fast and efficient short read mapping based on a succinct hash index.

BACKGROUND: Various indexing techniques have been applied by next generation sequencing read mapping tools. The choice of a particular data structure is a trade-off between memory consumption, mapping throughput, and construction time. RESULTS: We present the succinct hash index - a novel data structure for read mapping which is a variant of the classical q-gram index with a particularly small memory footprint occupying between 3.5 and 5.3 GB for a human reference genome for typical parameter settings. The succinct hash index features two novel seed selection algorithms (group seeding and variable-length seeding) and an efficient parallel construction algorithm, which we have implemented to design the FEM (Fast(F) and Efficient(E) read Mapper(M)) mapper. FEM can return all read mappings within a given edit distance. Our experimental results show that FEM is scalable and outperforms other state-of-the-art all-mappers in terms of both speed and memory footprint. Compared to Masai, FEM is an order-of-magnitude faster using a single thread and two orders-of-magnitude faster when using multiple threads. Furthermore, we observe an up to 2.8-fold speedup compared to BitMapper and an order-of-magnitude speedup compared to BitMapper2 and Hobbes3. CONCLUSIONS: The presented succinct index is the first feasible implementation of the q-gram index functionality that occupies around 3.5 GB of memory for a whole human reference genome. FEM is freely available at https://github.com/haowenz/FEM .