Miracle-dz/UniFAR-FTUs huggingface dataset:
Earlier surgery improves outcomes from painful chronic pancreatitis

Abstract The timing of surgery for painful chronic pancreatitis (CP) may affect outcomes. Clinical course, Izbicki pain scores, and pancreatic function were retrospectively compared and analyzed between patients undergoing either early or late surgery (< 3 or ≥ 3 years from diagnosis) for painful CP in a single center from 2007 to 2012. The early surgery group (n = 98) more frequently than the late group (n = 199) had abdominal pain with jaundice (22.4% vs 9.5%, P = .002) and pancreatic mass +/− ductal dilatation (47% vs 27%, P < .001), but less frequently abdominal pain alone (73.5% vs 85.9%, P = .009), ductal dilatation alone (31% vs 71%, P < .001), parenchymal calcification (91.8% vs 100%, P < .001) or exocrine insufficiency (60% vs 72%, P = .034); there were no other significant differences. The early group had longer hospital stay (14.4 vs 12.2 days, P = .009), but no difference in complications. Significantly greater pain relief followed early surgery (complete 69% vs 47%, partial 22% vs 37%, none 8% vs 16%, P = .01) with lower rates of exocrine (60% vs 80%, P = .005) and endocrine insufficiency (36% vs 53%, P = .033). Our data indicate that early surgery results in higher rates of pain relief and pancreatic sufficiency than late surgery for chronic pancreatitis patients. Frey and Berne procedures showed better results than other surgical procedures.
A Review on "The Second Decade of Education for Africa (2006～2015) Plan of Action"

The African Union issued "The Second Decade of Education for Africa(2006～2015)Plan of Action" in the process of the integration of African education.The plan aimed at developing the information system of education management in African countries,constructing the effective mechanism for the integration of regional education,making education the main topic of African Union and regional economic communities,improving the educational performance significantly and realizing the gender equality.The Plan was an important milestone in the process of integration of African education.The plan had accelerated the creation of follow-up Plan of Action at all levels of education in Africa,reflected the current international advanced education concepts and aspirations,emphasized and conceived the localization of African education.
Minimal Important Difference in Voice Handicap Index–10

Importance The minimal important difference (MID) on patient-reported outcome measures can indicate how much of a change on that scale is meaningful. Objective To use an anchor-based approach to estimate MID in the Voice Handicap Index–10 (VHI-10) total score. Design, Setting, and Participants In this cohort study, a volunteer sample of adult patients visiting the voice clinic at the University of Minnesota from April 7, 2013, through July 3, 2016, completed the VHI-10 (range, 0-40, with higher scores indicating greater voice-related handicap) at baseline and 2 weeks later in conjunction with a global rating of change. An anchor-based approach was used to identify an MID. The association between the global change score and change in VHI-10 score was analyzed using Pearson rank correlation. A distribution-based method was used to corroborate the findings. Main Outcome and Measures Global rating of change on the VHI-10. Results Of the 273 participants, 183 (67.0%) were women and 90 (33.0%) were men (mean [SD] age, 54.3 [15.6] years); 259 (94.9%) were white. Participants had a variety of voice disorders, most commonly muscle tension dysphonia, irritable larynx, benign vocal fold lesions, and motion abnormalities. Among patients reporting no change on the global change score, the mean (SD) change in VHI-10 score was 1 (5). Among those reporting a small change, the mean (SD) change in VHI-10 was also 1 (5). Among those reporting a moderate change in voice symptoms, the mean (SD) change in VHI-10 score was 6 (8). Among those with a large change, the mean (SD) change in VHI-10 score was 9 (13). The correlation between the global change score and the change in VHI-10 score was 0.32 (95% CI, 0.12-0.49). Distribution-based analyses identified effect sizes comparable to those of the anchor-based categories. Conclusions and Relevance These findings suggest that a difference of 6 on the VHI-10 may represent an MID. This difference was associated with a moderate change on the global rating scale, and the small-change and no-change categories were indistinguishable. Given the lack of differentiation between small and no change and the modest correlation between the global change score and change in the VHI-10 score, additional studies are needed.
External validation of predictive models for acute kidney injury following cardiac surgery: A prospective multicentre cohort study

BACKGROUND Four predictive models for acute kidney injury associated with cardiac surgery were developed by Demirjian in the United States in 2012. However, the usefulness of these models in clinical practice needs to be established in different populations independent of that used to develop the models. OBJECTIVES Our aim was to evaluate the predictive performance of these models in a Spanish population. DESIGN A multicentre, prospective observational study. DATA SOURCES Twenty-three Spanish hospitals in 2012 and 2013. ELIGIBILITY CRITERIA Of 1067 consecutive cardiac patients recruited for the study, 1014 patients remained suitable for the final analysis. MAIN OUTCOME MEASURES Dialysis therapy, and a composite outcome of either a doubling of the serum creatinine level or dialysis therapy, in the 2 weeks (or until discharge, if sooner) after cardiac surgery. RESULTS Of the 1014 patients analysed, 34 (3.4%) required dialysis and 95 (9.4%) had either dialysis or doubled their serum creatinine level. The areas under the receiver operating characteristic curves of the two predictive models for dialysis therapy, which include either presurgical variables only, or combined presurgical and intrasurgical variables, were 0.79 and 0.80, respectively. The model for the composite endpoint that combined presurgical and intrasurgical variables showed better discriminatory ability than the model that included only presurgical variables: the areas under the receiver operating characteristic curves were 0.76 and 0.70, respectively. All four models lacked calibration for their respective outcomes in our Spanish population. CONCLUSION Overall, the lack of calibration of these models and the difficulty in using the models clinically because of the large number of variables limit their applicability.
A resolution adaptive deep hierarchical (RADHicaL) learning scheme applied to nuclear segmentation of digital pathology images

Deep learning (DL) has recently been successfully applied to a number of image analysis problems. However, DL approaches tend to be inefficient for segmentation on large image data, such as high-resolution digital pathology slide images. For example, typical breast biopsy images scanned at 40 magnification contain billions of pixels, of which usually only a small percentage belong to the class of interest. For a typical naïve deep learning scheme, parsing through and interrogating all the image pixels would represent hundreds if not thousands of hours of compute time using high performance computing environments. In this paper, we present a resolution adaptive deep hierarchical (RADHicaL) learning scheme wherein DL networks at lower resolutions are leveraged to determine if higher levels of magnification, and thus computation, are necessary to provide precise results. We evaluate our approach on a nuclear segmentation task with a cohort of 141 ER+ breast cancer images and show we can reduce computation time on average by about 85%. Expert annotations of 12,000 nuclei across these 141 images were employed for quantitative evaluation of RADHicaL. A head-to-head comparison with a naïve DL approach, operating solely at the highest magnification, yielded the following performance metrics: . 9407 vs . 9854 Detection Rate, . 8218 vs . 8489 F-score, . 8061 vs . 8364 true positive rate and . 8822 vs 0.8932 positive predictive value. Our performance indices compare favourably with state of the art nuclear segmentation approaches for digital pathology images.
Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries

Summary Blood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.
USP11 Enhances TGFβ-Induced Epithelial–Mesenchymal Plasticity and Human Breast Cancer Metastasis

Epithelial–mesenchymal transition (EMT) is a conserved cellular plasticity program that is reactivated in carcinoma cells and drives metastasis. Although EMT is well studied its regulatory mechanisms remain unclear. Therefore, to identify novel regulators of EMT, a data mining approach was taken using published microarray data and a group of deubiquitinases (DUB) were found to be upregulated in cells that have undergone EMT. Here, it is demonstrated that one DUB, ubiquitin-specific peptidase 11 (USP11), enhances TGFβ-induced EMT and self-renewal in immortalized human mammary epithelial cells. Furthermore, modulating USP11 expression in human breast cancer cells altered the migratory capacity in vitro and metastasis in vivo. Moreover, elevated USP11 expression in human breast cancer patient clinical specimens correlated with decreased survival. Mechanistically, modulating USP11 expression altered the stability of TGFβ receptor type II (TGFBR2) and TGFβ downstream signaling in human breast cancer cells. Together, these data suggest that deubiquitination of TGFBR2 by USP11 effectively spares TGFBR2 from proteasomal degradation to promote EMT and metastasis. Implications: USP11 regulates TGFβ-induced epithelial–mesenchymal plasticity and human breast cancer metastasis and may be a potential therapeutic target for breast cancer. Mol Cancer Res; 16(7); 1172–84. ©2018 AACR.
Cotargeting of MEK and PDGFR/STAT3 Pathways to Treat Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal human diseases and remains largely refractory to available drug treatments. Insufficient targeting of the known oncogenic drivers and activation of compensatory feedback loops and inability to prevent metastatic spread contribute to poor prognosis for this disease. The KRAS-driven MEK pathway is mutationally activated in most pancreatic cancers and is an important target for therapeutics. Using a two-dimensional monolayer culture system as well as three-dimensional spheroid culture system, we conducted a screen of a large panel of anticancer agents and found that MAP2K (MEK) inhibitors were most effective in targeting PDAC spheroids in comparison with monolayer cultures. Combination treatment with an MEK inhibitor and the multikinase inhibitor ponatinib was effective in targeting pancreatic cancer cells both in monolayer and spheroids by effectively blocking signaling via the PDGFRα and MEK kinases, while also preventing the activation of STAT3- and S6-mediated compensatory feedback loops in cancer cells. Furthermore, using xenograft models, we demonstrate that cotreatment with a MEK inhibitor and ponatinib causes significant tumor regression. PDAC patient samples also provided evidence of increased STAT3 activation in PDAC tumors and MAPK1 (ERK) activation in liver metastases, implicating STAT3 and ERK as key drivers in primary tumors and metastases, respectively. These results reveal a combination drug treatment strategy that may be effective in pancreatic cancer. Mol Cancer Ther; 16(9); 1729–38. ©2017 AACR.
Dissecting the pathological effects of human Aβ40 and Aβ42 in Drosophila: A potential model for Alzheimer's disease

Accumulation of amyloid-β (Aβ) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human Aβ40 or Aβ42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of Aβ42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of Aβ40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of Aβ42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying Aβ toxicity and the discovery of novel therapeutic targets for AD.
Occupational Noise Exposure, Bilateral High-Frequency Hearing Loss, and Blood Pressure

Objective: The aim of this study was to investigate the relationships between occupational noise exposure and blood pressure using self-reported occupational exposure and bilateral high-frequency hearing loss. Methods: This study included 4548 participants aged 20 to 69 years from the National Health and Nutrition Examination Survey 1999 to 2004. On the basis of self-reported exposure status, participants were divided into the current, former, or never exposed groups. Bilateral high-frequency hearing loss was defined as the average high-frequency hearing threshold at least 25 dB in both ears. Results: The currently exposed participants had slightly increased diastolic blood pressure compared with those never exposed. Among previously exposed participants, those with bilateral high-frequency hearing loss had increased systolic blood pressure, heart rate, and the prevalence of hypertension compared with those with normal high-frequency hearing. Conclusion: Although there were some significant results, the evidence was not consistent to support the associations between occupational noise exposure and blood pressure.
Down-Regulation of Love Feelings After a Romantic Break-Up: Self-Report and Electrophysiological Data

Because remaining love feelings for an ex-partner are negatively associated with recovery from a romantic break-up, it may be helpful to decrease those love feelings. Love regulation is the use of behavioral or cognitive strategies to change the intensity of current feelings of romantic love. This study evaluated three regulation strategies: (1) negative reappraisal of the ex-partner, (2) reappraisal of love feelings, and (3) distraction. It was tested how these regulation strategies change love feelings for the ex-partner, valence of affect, and motivated attention for the ex-partner. Participants who were upset about a romantic break-up performed these regulation strategies before passively viewing a picture of their ex-partner, during which their electroencephalogram was recorded. Negative reappraisal decreased love feelings and made participants feel more unpleasant. Love reappraisal did not change how in love or pleasant/unpleasant participants felt. Distraction did not change love feelings but made participants feel more pleasant. This suggests that in the context of a romantic break-up, negative reappraisal is an effective love down-regulation strategy, whereas distraction is an effective positive emotion up-regulation strategy. Furthermore, all three strategies decreased motivated attention for the ex-partner, as indicated by a reduced amplitude of the late positive potential. This reduced motivated attention for the ex-partner could make it easier to deal with encounters of (reminders of) the ex-partner. Love regulation is a promising phenomenon with important everyday life and clinical implications.
A simplified multivisceral transplantation procedure for patients with combined end‐stage liver disease and type 2 diabetes mellitus

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end‐stage liver disease and concurrent type 2 DM. Forty‐four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1‐, 3‐, and 5‐year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end‐stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161–1170 2017 AASLD.
Molecular imaging with positron emission tomography and computed tomography (PET/CT) for selecting first-line targeted treatment in metastatic breast cancer: a cost-effectiveness study

Our aim was to evaluate the potential cost-effectiveness of PET/CT with FES and 89Zr-trastuzumab compared to pathology to select first-line targeted treatment in metastatic breast cancer (MBC) patients with non-rapidly progressive disease. A previously published and validated model was extended and adapted for this analysis. Two alternative scenarios were compared. In the care as usual pathway first-line targeted treatment of MBC patients was assigned on the basis of pathology results, while in the intervention pathway treatment selection was based on the results from the PET/CT imaging. Costs, life years gained (LYG) and incremental cost-effectiveness ratios (ICER) were calculated. More MBC lesions were detected in the intervention pathway than in the care as usual pathway. The diagnostic costs to evaluate the receptor status and the treatment costs were higher in the intervention strategy, as were total costs and total LYG. The ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab, assuming sensitivity of 77.1% and specificity of 80%, ranged from €71,000 to €77,000 per LYG. When assuming sensitivity of 80% and specificity of 76.7%, the ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab ranged from to €74,000 to €80,000 per LYG. The application of PET/CT with FES and 89Zr-trastuzumab in first-line treatment selection for MBC patients has the potential to be a cost-effective intervention. Our analysis demonstrated that even a small increase in the sensitivity and the specificity of PET/CT can have a large impact on its potential cost-effectiveness.
Prediction of PEMFC stack efficiency using recurrent neural networks

Hydrogen-related technologies are a promising solution for energy storage systems. The energy surplus from renewables or the off-peak power in a centralized electric system can be used to feed an electrolyzer to produce hydrogen. Then, the stored hydrogen can be converted to electric energy using proton exchange membrane fuel cells (PEMFCs), which have higher efficiency than other conventional energy conversion technologies. However, a PEMFC stack might be subject to variations in its energy conversion efficiency due to undesirable changes in the internal operating conditions, which may lead to a relatively high loss of generation capacity and an increase in the hydrogen consumption. A system identification method using recurrent neural networks (RNNs) able to build prediction models for the efficiency is proposed in this paper aiming at a further use in a control application to maximize the stack's efficiency in real-time. A 3 kW commercial PEMFC stack operating under a typical residential load profile is employed in this work to obtain experimental data. Three models are developed with the aforementioned method using data sets with different sizes for training the RNNs. The results show good agreement between the predicted and the measured efficiency, with a coefficient of determination (R2 coefficient) higher than 0.999 and a validation mean squared error (MSE) lower than 0.02 for most of the models. The results also reveal that, for a fixed prediction horizon of 6.4 h, all the three models present similar performance, with the size of the training data sets making little difference in the performance indicators.
Protein-Induced Fluorescence Enhancement Based Detection of Plasmodium falciparum Glutamate Dehydrogenase Using Carbon Dot Coupled Specific Aptamer.

A novel 90-mer long ssDNA aptamer (NG3) covering a 40-mer random region targeting Plasmodium falciparum glutamate dehydrogenase ( PfGDH) developed through systematic evolution of ligands by exponential enrichment (SELEX) technique. The binding affinity of the aptamer to PfGDH discerned by circular dichroism (CD) was 0.5 ± 0.04 μM. The specificity of the aptamer toward the target was confirmed by gel electrophoresis and CD studies. The presence of two quadruplex forming regions, two big and four small stem loop structures with a δG of -7.99 kcal mol-1 for NG3 were deduced by computational studies. The spherical carbon dots (Cdots) of size 2-4 nm, synthesized by pyrolysis method using l-glutamate as a substrate were covalently linked to the amine modified aptamer. The Cdot with a band gap of 2.8 eV and a quantum yield of 34% produced fluorescence at ∼ λ410 nm when excited at λ320nm. The quantum yield of Cdot-aptamer assembly was increased up to 40% in the presence of the PfGDH in solution. A linear relationship with a dynamic range of 0.5 nM to 25 nM (R2 = 0.98) and a limit of detection (LOD) of 0.48 nM was observed between the fluorescence intensity of the Cdots-aptamer conjugate and the concentration of PfGDH. The method could detect PfGDH with an LOD of 2.85 nM in diluted serum sample. This novel simple, sensitive and specific protein induced fluorescence enhancement based detection of PfGDH has a great potential to develop as a method for malaria detection.