Miracle-dz/UniFAR-FTUs huggingface dataset:
Sox12, a direct target of FoxQ1, promotes hepatocellular carcinoma metastasis through up‐regulating Twist1 and FGFBP1

Metastasis is the main reason for high recurrence and poor survival of hepatocellular carcinoma (HCC) after curative resection. However, the molecular mechanism underlying HCC metastasis remains unclear. Here, we report on a novel function of SRY (sex determining region Y)‐box 12 (Sox12), a member of the SYR‐related high mobility group box family proteins, in promoting HCC metastasis. Overexpression of Sox12 was significantly correlated with loss of tumor encapsulation, microvascular invasion, and a higher tumor‐nodule‐metastasis (TNM) stage and indicated poor prognosis in human HCC patients. Sox12 expression was an independent and significant risk factor for recurrence and reduced survival after curative resection. Overexpression of Sox12 induced epithelial‐mesenchymal transition by transactivating Twist1 expression. Down‐regulation of Twist1 decreased Sox12‐enhanced HCC migration, invasion, and metastasis, whereas up‐regulation of Twist1 rescued the decreased migration, invasion, and metastasis induced by Sox12 knockdown. Additionally, serial deletion, site‐directed mutagenesis, and chromatin immunoprecipitation assays showed that fibroblast growth factor binding protein 1 (FGFBP1) was a direct transcriptional target of Sox12. Knockdown of FGFBP1 decreased Sox12‐mediated HCC invasion and metastasis, whereas overexpression of FGFBP1 rescued the decreased invasion and metastasis induced by Sox12 knockdown. Furthermore, forkhead box Q1 (FoxQ1) directly bound to the Sox12 promoter and transactivated its expression, which contributed to Sox12 overexpression in human HCC. Knockdown of Sox12 dramatically decreased FoxQ1‐mediated HCC metastasis. In two independent cohorts of human HCC tissues, Sox12 expression was positively correlated with Twist1, FGFBP1, and FoxQ1 expression, and patients with positive coexpression of Sox12/Twist1, Sox12/FGFBP1, or FoxQ1/Sox12 were associated with poorer prognosis. Conclusion: Up‐regulated Sox12 induced by FoxQ1 promotes HCC invasion and metastasis by transactivating Twist1 and FGFBP1 expression. Thus, our study implicates Sox12 as a potential prognostic biomarker and a novel therapeutic target for HCC. (Hepatology 2015;61:1920–1933)
Reliability of Spike Timing Is a General Property of Spiking Model Neurons

The responses of neurons to time-varying injected currents are reproducible on a trial-by-trial basis in vitro, but when a constant current is injected, small variances in interspike intervals across trials add up, eventually leading to a high variance in spike timing. It is unclear whether this difference is due to the nature of the input currents or the intrinsic properties of the neurons. Neuron responses can fail to be reproducible in two ways: dynamical noise can accumulate over time and lead to a desynchronization over trials, or several stable responses can exist, depending on the initial condition. Here we show, through simulations and theoretical considerations, that for a general class of spiking neuron models, which includes, in particular, the leaky integrate-and-fire model as well as nonlinear spiking models, aperiodic currents, contrary to periodic currents, induce reproducible responses, which are stable under noise, change in initial conditions and deterministic perturbations of the input. We provide a theoretical explanation for aperiodic currents that cross the threshold.
Enabling Annotation of Historical Corpora in an Asynchronous Collaborative Environment

Current research in Corpus Linguistics and related disciplines within the multi-disciplinary field of Digital Humanities, involves computer-aided manual processing of large text corpora. Typically, corpus instances are retrieved with the help of concordancers and textual search engines and subsequently labeled by hand before being submitted to quantitative analysis. While well-established software solutions already exist for corpus data retrieval, less attention has been paid to the annotation process in terms of both software facilities and best practices, especially in the context of collaborative research. However, with the increase in size and scope of research projects we envisage new needs for synchronizing interdependent annotations by different researchers. Current ad-hoc solutions to collaborative corpus analysis and annotation typically involve general-purpose Real-Time Editing (RTE) and cloud storage software, whose functionality is arguably sub-optimal for research purposes. In the present paper we discuss potential problems related to synchronizing annotations in large-scale projects, as well as the potential benefits that can be derived from a dedicated approach to annotation data management. As a proof of concept, we showcase our current solution in the form of Cosycat (Collaborative Synchronized Corpus Annotation Tool), a collaborative asynchronous application that has grown out of a Historical Linguistics research project involving several parallel studies and multiple researchers.
The psychometric properties, sensitivity and specificity of the geriatric anxiety inventory, hospital anxiety and depression scale, and rating anxiety in dementia scale in aged care residents

ABSTRACT Objectives: Limited research has been conducted into the identification of a valid and reliable screening measure for anxiety in aged care settings, despite it being one of the most common psychological conditions. This study aimed to determine an appropriate anxiety screening tool for aged care by comparing the reliability and validity of three commonly used measures and identifying specific cut-offs for the identification of generalized anxiety disorder (GAD). Method: One-hundred and eighty nursing home residents (M age = 85.39 years) completed the GAI, HADS-A, and RAID, along with a structured diagnostic interview. Results: Twenty participants (11.1%) met DSM-5 criteria for GAD. All measures had good psychometric properties , although reliability estimates for the HADS-A were sub-optimal. Privileging sensitivity , the GAI cut-off score of 9 gave sensitivity of 90.0% and specificity of 86.3%; HADS-A cut-off of 6 gave sensitivity of 90.0% and specificity of 80.6%; and RAID cut-off of 11 gave sensitivity of 85.0% and specificity of 72.5%. Conclusion: While all three measures had adequate reliability, validity, and cut-scores with high levels of sensitivity and specificity to detect anxiety within aged care, the GAI was the most consistently reliable and valid measure for screening for GAD.
Clinical adequacy assessment of autocontours for prostate IMRT with meaningful endpoints

Purpose To determine if radiation treatment plans created based on autosegmented (AS) regions‐of‐interest (ROI)s are clinically equivalent to plans created based on manually segmented ROIs, where equivalence is evaluated using probabilistic dosimetric metrics and probabilistic biological endpoints for prostate IMRT. Method and materials Manually drawn contours and autosegmented ROIs were created for 167 CT image sets acquired from 19 prostate patients. Autosegmentation was performed utilizing Pinnacle's Smart Probabilistic Image Contouring Engine. For each CT set, 78 Gy/39 fraction 7‐beam IMRT treatment plans with 1 cm CTV‐to‐PTV margins were created for each of the three contour scenarios; PMD using manually delineated (MD) ROIs, PAS using autosegmented ROIs, and PAM using autosegmented organ‐at‐risks (OAR)s and the manually drawn target. For each plan, 1000 virtual treatment simulations with different systematic errors for each simulation and a different random error for each fraction were performed. The statistical probability of achieving dose–volume metrics (coverage probability (CP)), expectation values for normal tissue complication probability (NTCP), and tumor control probability (TCP) metrics for all possible cross‐evaluation pairs of ROI types and planning scenarios were reported. In evaluation scenarios, the root mean square loss (RMSL) and maximum absolute loss (MAL) of coverage probability of dose–volume objectives, E[TCP], and E[NTCP] were compared with respect to the base plan created and evaluated with manually drawn contours. Results Femoral head dose objectives were satisfied in all situations, as well as the maximum dose objectives for all ROIs. Bladder metrics were within the clinical coverage tolerances except D35Gy for the autosegmented plan evaluated with the manual contours. Dosimetric indices for CTV and rectum could be highly compromised when the definition of the ROIs switched from manually delineated to autosegmented. Seventy‐two percent of CT image sets satisfied the worst‐case CP thresholds for all dosimetric objectives in all scenarios, the percentage dropped to 50% if biological indices were taken into account. Among evaluation scenarios, (MD,PAM) bore the highest resemblance to (MD,PMD) where 99% and 88% of cases met all CP thresholds for bladder and rectum, respectively. Conclusions When including daily setup variations in prostate IMRT, the dose–volume metric CP, and biological indices of ROIs were approximately equivalent for the plans created based on manually drawn targets and autosegmented OARs in 88% of cases. The accuracy of autosegmented prostates and rectums are impediment to attain statistically equivalent plans created based on manually drawn ROIs.
Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian patients with chronic hepatitis C: a real-world experience

Background Simeprevir plus sofosbuvir (SIM/SOF) regimen was recommended by professional guidelines for certain patients with HCV genotype 1 infection and there is lack of data about this regimen in patients with genotype 4 infection. Aim To evaluate the efficacy and safety of this regimen in Egyptian patients with chronic HCV genotype 4 infection in the real world. Methods Multicentre observational study included 583 patients with HCV genotype 4 infection who began 12 weeks of treatment with SIM plus SOF. Demographic, clinical and virological data as well as adverse outcomes were collected. Treatment naïve patients were 342 (59%) of all included patients, 45% of patients had severe fibrosis (F3 and F4) while 55% had mild fibrosis (F1 and F2) and the primary outcome was sustained virological response (SVR). Results The overall SVR rate was 95.7% (558 out of 583 patients). In total, SVR12 in naïve patients with mild fibrosis score (F1 and F2) was achieved in 98.9% (94/95) for F1 and 98.1% (105/107) for F2, while naïve patients with severe fibrosis (F3 and F4) achieved SVR of 97.7% (86/88) for F3 and (42/52) 80.8% for F4. SVR in patients with previous interferon treatment achieved in 100% (45/45) for patients with F1 and 98.7% (74/75) for F2. While 94.7% (72/76) in experienced patients with F3; and 88.9% (40/45) for F4 achieved SVR12. Notable side effects included rash in 21 patients, photosensitivity in 18 patients, pruritus in 44 patients and hyperbilirubinemia in 42 patients. Conclusions A 12-week regimen of simeprevir/sofosbuvir was efficacious and well tolerated by treatment-naïve and treatment-experienced patients with chronic HCV genotype 4.
Resilient Moduli of Reclaimed Asphalt Pavement Aggregate Subbase Blends

AbstractThis paper investigates the resilient moduli of reclaimed asphalt pavement (RAP) and virgin aggregate blends obtained from the subbase of a segment of Route 165 in Rhode Island, U.S. The materials included RAP and virgin aggregates that were blended off-site using cold recycled RAP, as well as RAP blends that were generated in situ from full-depth reclamation (FDR). Cyclic triaxial tests were performed on compacted specimens of the RAP blends to assess their resilient modulus (MR) behavior. Selected FDR RAP blends were mixed with various stabilizer treatments including liquid calcium chloride, asphalt emulsion, or portland cement. A three-parameter material model was fit to the laboratory test data and used to interpret the MR behavior. The MR values of the untreated cold recycled RAP blends and the untreated FDR RAP blends ranged from 120 to 502 MPa and 171 to 578 MPa, respectively. The MR values of the calcium chloride-treated and asphalt emulsion-treated FDR RAP blends were within the range of .
A 45 nm Stacked CMOS Image Sensor Process Technology for Submicron Pixel †

A submicron pixel’s light and dark performance were studied by experiment and simulation. An advanced node technology incorporated with a stacked CMOS image sensor (CIS) is promising in that it may enhance performance. In this work, we demonstrated a low dark current of 3.2 e−/s at 60 °C, an ultra-low read noise of 0.90 e−·rms, a high full well capacity (FWC) of 4100 e−, and blooming of 0.5% in 0.9 μm pixels with a pixel supply voltage of 2.8 V. In addition, the simulation study result of 0.8 μm pixels is discussed.
The acute effect of continuous positive airway pressure titration on blood pressure in awake overweight/obese patients with obstructive sleep apnoea

Abstract Objectives: Continuous positive airway pressure (CPAP) improves upper airway obstruction in patients with obstructive sleep apnoea (OSA), who often are overweight-obese. Although it is thought that CPAP improves long-term blood pressure control (BP), the impact of acute and short-term CPAP use on the cardiovascular system in obese patients has not been described in detail. Methods: Obese patients (body mass index, BMI > 25 kg/m2) with OSA were studied awake, supine during incremental CPAP titration (4–20 cmH2O, +2 cmH2O/3 mins). BP was measured continuously with a beat-to-beat BP monitor (Ohmeda 2300, Finapres Medical Systems, Amsterdam/NL), BP variability (BPV) was calculated as the standard deviation of BP at each CPAP level, the 95% confidence interval (95%CI) was calculated and changes in BP and BPV were reported. Results: 15 patients (12 male, 48 ± 10) years, BMI 38.9 ± 5.8 kg/m2) were studied; the baseline BP was 131.0 ± 10.2/85.1 ± 9.1 mmHg. BP and BPV increased linearly with CPAP titration (systolic BP r = 0.960, p < .001; diastolic BP r = 0.961, p < .001; systolic BPV r = 0.662, p = .026; diastolic BPV r = 0.886, p < .001). The systolic BP increased by +17% (+23.15 (7.9, 38.4) mmHg; p = . 011) and the diastolic BP by +23% (+18.27 (2.33, 34.21) mmHg; p = . 009), when titrating CPAP to 20 cmH2O. Systolic BPV increased by +96% (+5.10 (0.67, 9.53) mmHg; p < . 001) and was maximal at 14 cmH2O, and diastolic BPV by +97% (+3.02 (0.26, 5.78) mmHg; p < . 001) at 16 cmH2O. Conclusion: Short-term incremental CPAP leads to significant increases in BP and BPV in obese patients with OSA while awake. Careful titration of pressures is required to minimise the risk of nocturnal awakenings while improving BP control.
Fibroblast growth factor 23 dysregulates late sodium current and calcium homeostasis with enhanced arrhythmogenesis in pulmonary vein cardiomyocytes

Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0.1 or 1 ng/mL) incubation for 4~6 h. Compared to the control, FGF23 (1 ng/mL, but not 0.1 ng/mL)-treated PV cardiomyocytes had a faster beating rate. FGF23 (1 ng/mL)-treated PV cardiomyocytes had larger INa-Late, calcium transients, and mitochondrial ROS than controls. However, ranolazine (an inhibitor of INa-Late) attenuated FGF23 (1 ng/mL)-increased beating rates, calcium transients and mitochondrial ROS. FGF23 (1 ng/mL)-treated PV cardiomyocytes exhibited larger phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII). Chelerythrine chloride (an inhibitor of protein kinase C) decreased INa-Late in FGF23 (1 ng/mL)-treated PV cardiomyocytes. However, KN93 (a selective CaMKII blocker) decreased INa-Late in control and FGF23 (1 ng/mL)-treated PV cardiomyocytes to a similar extent. In conclusion, FGF23 increased PV arrhythmogenesis through sodium and calcium dysregulation by acting protein kinase C signaling.
Outcomes of High Risk Patients with Febrile Neutropenia at a Tertiary Care Center

Fever during chemotherapy-induced neutropenia continues to be a major cause of morbidity and mortality in cancer patients. Mortality depends on the duration and degree of neutropenia, bacteremia, sepsis, performance status, comorbidities and other parameters. The highest mortality rates in cancer patients hospitalized with febrile neutropenia (FN) are observed in those with documented infection. The objectives of the study were to present available tools for risk assessment, to review pathogens causing infections in adult FN patients and to assess outcomes. Methods: This cross sectional study was conducted on adult culture positive FN patients admitted to the Hematology/Oncology service at the Aga Khan University Hospital, Karachi, Pakistan from 1st January 2009 to 31st December 2012. High-risk criteria were defined as profound neutropenia, short latency from a previous chemotherapy cycle, sepsis or clinically documented infection at presentation, severe co-morbidity and a performance status greater than or equal to 3. All types of organisms in blood culture and the outcomes of the patients were recorded on Proforma. Results: A total of 156 patients with culture-positive febrile neutropenia were identified during the study period. The mean age was 47 years with a slight male predominance of 54%. One hundred and sixteen patients fulfilled the criteria for the high risk group. Fifty two percent had a single high risk factor and 40 % had two. All patients harbored either single or multiple bacterial organisms including gram positive, gram negative or both types. Some 34% of patients had gram positive bacteremia, 57 % had gram negative and 9 % were infected with both. Among 73 gram positive cultures 44 % were Staphylococcus species and among 123 gram negative cultures 43 % were E. coli. One hundred and fifteen patients recovered uneventfully and could be discharged. Thirty two patients in the high risk and 9 in the low risk groups deceased with an overall mortality of 26 %. The mean hospital stays of patients with solid tumors and hematological malignancies were 7.58 and 15.0 days, respectively. Mortality was higher in the latter group, and also in high risk patients with both gram positive and negative bacteremia. Conclusion: We emphasize the importance of risk stratification and continuous surveillance of the spectrum of locally prevalent pathogens and their susceptibility patterns for formulation of therapeutic regimens for febrile neutropenic patients.
METs and accelerometry of walking in older adults: standard versus measured energy cost.

PURPOSE This study aimed to measure the metabolic cost (METs) of walking activities in older adults, to examine the relationship between accelerometer output and METs across walking activities, and to compare measured MET values in older adults with the MET values in the compendium. METHODS Twenty older adults (mean age = 75, range = 60-90 yr) completed eight walking activities (five treadmill based, three free living) for 6 min each. Oxygen consumption (V˙O2) and resting metabolic rate (RMR) were measured using a portable metabolic system, and motion was recorded using a waist-mounted ActiGraph accelerometer (GT3X; ActiGraph, Pensicola, FL). Energy expenditure across activities was defined as kilocalories per minute and measured as METs (V˙O2 / RMR) and standard METs (V˙O2 / 3.5 mL·kg-1·min-1). Mixed modeling was used to assess differences in counts per minute and kilocalories per minute by weight status, sex, comorbidity status, and functional status. Linear regression analysis was applied to develop a prediction equation for kilocalories per minute. Energy costs of walking were subsequently compared with METs in the compendium of physical activities. RESULTS Average measured RMR was 2.6 mL·kg-1·min-1, 31.6% less than the standard RMR of 3.5 mL·kg-1·min-1. On average, standard METs were 71% lower than the measured METs across all walking activities. Measured MET levels differed from previously reported values in the literature and values listed in the compendium, resulting in misclassification of activity intensities for 60% of the walking conditions. Average counts for the walking activities ranged from 809 (treadmill = 1.5 mph) to 4593 counts per minute (treadmill = 3.5 mph). Previous regression equations consistently overestimate all activities compared with the measured energy cost in this sample of older adults. CONCLUSION This study identifies the need for equations and cut points specific to older adults.
Brief Report: Antibody Responses to Quadrivalent HPV Vaccination in HIV-Infected Young Women as Measured by Total IgG and Competitive Luminex Immunoassay

Abstract: We compared antibody responses of HIV-infected young women to the human papillomavirus (HPV) 6, 11, 16, and 18 vaccine using total immunoglobulin (Ig) G Luminex immunoassay (LIA) and competitive Luminex immunoassay (cLIA) assays. HPV18 seropositivity after HPV vaccination as measured with IgG LIA remained high (98%) 48 weeks after vaccination, in contrast with seropositivity as measured with cLIA (73%). Seropositivity rates at week 48 as measured by both IgG LIA and cLIA remained high for HPV6, 11, and 16 (93.5%–100%). These results suggest that the lower rate of seropositivity to HPV18 when cLIA vs. IgG LIA is used is a function of the assay and does not imply lower vaccine immunogenicity.
Behavior and health beliefs as predictors of HIV testing among women: a prospective study of observed HIV testing

ABSTRACT Much of the research examining predictors of HIV testing has used retrospective self-report to assess HIV testing. Findings. therefore, may be subject to recall bias and to difficulties determining the direction of associations. In this prospective study, we administered surveys to women in community clinics to identify predictors of subsequent observed HIV testing, overcoming these limitations. Eighty-three percent were tested. In the adjusted multivariable model, being born in the U.S., perceived benefits of testing, worries about being infected with HIV, having had more than 15 lifetime sexual partners, and having had one or more casual sexual partners in the previous three months predicted acceptance of testing. Perceived obstacles to testing predicted non-acceptance. Those who had never been tested for HIV and those tested two to five years previously had greater odds of test acceptance than those who had been tested within the last year. The findings from this study with observed testing as the outcome, confirm some of the results from retrospective, self-report studies. Participants made largely rational decisions about testing, reflecting assessments of their risk and their history of HIV testing. Health beliefs are potentially modifiable through behavioral intervention, and such interventions might result in greater acceptance of testing. Abbreviations: HIV: human immunodeficiency virus; AIDS: acquired immune deficiency syndrome; CDC: Centers for Disease Control and Prevention; ACASI: audio computer-assisted self-interview; TRA: theory of reasoned action; HBM: Health Belief Model; STI: sexually transmitted infection; STD: Sexually Transmitted Disease; AOR: adjusted odds ratio; CI: confidence interval