Miracle-dz/UniFAR-FTUs huggingface dataset:
SMAD4 alteration associates with invasive‐front pathological markers and poor prognosis in colorectal cancer

SMAD4 acts as a tumour suppressor, and the loss of SMAD4 is associated with poor prognosis in colorectal cancer (CRC) patients. Although next‐generation sequencing (NGS) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC.
Establishing age specific spirometry reference ranges for children/adolescents of Karachi, Pakistan: Randomized trials.

OBJECTIVE To establish age-specific normative spirometry reference range along with regression equation for children and adolescents. METHODS The cross-sectional study was conducted from April to October 2017, and comprised children and adolescents aged 7-18 years at 8 educational institutions representing various socio-economic strata of Karachi. A modified version of the International Study of Asthma and Allergies in Childhood Questionnaire was used. Spirometry variables including forced vital capacity, forced expiratory volume in 1 second, ratio between the two, peak expiratory flow rate, forced expiratory flow between 25% and 75% expired volume were recorded and interpreted. By normal distribution curve the reference values were established, and mean}2 standard deviation values were taken as significant. Pearson's correlation coefficient and linear regression models were calculated for all pulmonary variables with age. RESULTS Of the 751 subjects, 484(64.4%) were boys and 267(35.5%) were girls. The overall mean age was 12.96}2.8 years. The mean lung volume for forced vital capacity was 2.21}0.75, forced expiratory volume in 1 second 2.08}0.73, ratio between the two 92.9}4.7, peak expiratory flow 231.3 } 70.5 and forced expiratory flow between 25% and 75% expired volume was , , , 2.68}1.2. These lung volumes directly increased with age from children to adolescents (p<0.05). All variables showed a significant difference between boys and girls (p<0.05). CONCLUSIONS There was a linear positive correlation of age with lung function variables, while the boys presented higher values than the girls.
Twelve‐Lead ECG Optimization of Cardiac Resynchronization Therapy in Patients With and Without Delayed Enhancement on Cardiac Magnetic Resonance Imaging

Background Delayed enhancement (DE) on magnetic resonance imaging is associated with ventricular arrhythmias, adverse events, and worse left ventricular mechanics. We investigated the impact of DE on cardiac resynchronization therapy (CRT) outcomes and the effect of CRT optimization. Methods and Results We studied 130 patients with ejection fraction (EF) ≤40% and QRS ≥120 ms, contrast cardiac magnetic resonance imaging, and both pre‐ and 1‐year post‐CRT echocardiograms. Sixty‐three (48%) patients did not have routine optimization of CRT. The remaining patients were optimized for wavefront fusion by 12‐lead ECG. The primary end point in this study was change in EF following CRT. To investigate the association between electrical dyssynchrony and EF outcomes, the standard deviation of activation times from body‐surface mapping was calculated during native conduction and selected device settings in 52 of the optimized patients. Patients had no DE (n=45), midwall septal stripe (n=30), or scar (n=55). Patients without DE had better ∆EF (13±10 versus 4±10 units; P<0.01). Optimized patients had greater ∆EF in midwall stripe (2±9 versus 12±12 units; P=0.01) and scar (0±7 versus 5±10; P=0.04) groups, but not in the no‐DE group. Patients without DE had greater native standard deviation of activation times (P=0.03) and greater ∆standard deviation of activation times with standard programming (P=0.01). Device optimization reduced standard deviation of activation times only in patients with DE (P<0.01). Conclusions DE on magnetic resonance imaging is associated with worse EF outcomes following CRT. Device optimization is associated with improved EF and reduced electrical dyssynchrony in patients with DE.
Pengaruh Pengembangan Karir, Karakteristik Pekerjaan Dan Motivasi Berprestasi Terhadap Kinerja Pegawai Dengan Komitmen Sebagai Variabel Intervening Pada Kantor Pelayanan Pajak Pratama Pati

Beberapa permasalahannya antara lain kesetiaan pada perusahaan belum menjadi dasar dalam menentukan kemajuan karir pegawai, masih terdapat ambiguitas tugas, belum secara keseluruhan pegawai mempunyai rasa menyukai tantangan, belum optimalnya kinerja terlihat dari usaha mengembangkan kemampuan aktualisasi diri, memahami dan mengikuti instruksi yang diberikan, mempunyai inisiatif, kejujuran, kecerdasan, dan kehati-hatian. Jenis penelitian adalah testing hipotesis karena dalam penelitian ini dilakukan pengujian hipotesis, dengan menggunakan metode survey, dan dengan menggunakan data primer dan sekunder. Sampel dalam penelitian ini sebanyak 110 responden. Jenis dan sumber data yang digunakan adalah data primer dan sekunder. Pengumpulan data menggunakan wawancara, dan kuesioner. Uji instrumen menggunakan uji validitas dan uji reliabilitas. Teknik analisis yang digunakan adalah SEM (Structural Equation Modelling) Hasil penelitian menyimpulkan bahwa ada pengaruh yang signifikan antara pengembangan karir, motivasi berprestasi dan karakteristik pekerjaan terhadap komitmen organisasi, dan ada pengaruh pengembangan motivasi berprestasi, komitmen dan karakteristik pekerjaan terhadap kinerja.
Survival of patients with subglottic squamous cell carcinoma.

Objective Subglottic squamous cell carcinoma is a rare subsite of laryngeal cancer that behaves more aggressively and portends a worse prognosis. Using a population-based cancer registry, our objective was to report overall survival (os) and laryngectomy-free survival (lfs) in patients diagnosed with subglottic squamous cell carcinoma, and to determine whether primary laryngectomy results in improved survival. Methods This retrospective population-based study considered patients with a new diagnosis of squamous cell carcinoma in the province of Ontario over a 15-year period (1995-2009). The Ontario Cancer Registry was examined for patients with the diagnosis of interest during the period of interest. Linked population-based databases were used to obtain patient demographics, comorbidity measures, staging, survival, and primary treatment with laryngectomy. Results Of 4927 patients identified to have laryngeal carcinoma, 89 were defined as having primary subglottic carcinoma (1.8%). In the subglottic cohort, 68 patients were men (76.4%), and mean age at diagnosis was 68 years (interquartile range: 60-77 years). The 5-year os was 47.2%, and the 5-year lfs was 31.5%. In 13 patients (15%), the primary treatment was laryngectomy, which, compared with primary radiation, did not predict for improved os. No differences in os or lfs were observed during the 15-year study period (os p = 0.42, lfs p = 0.83). Conclusions The survival of patients with subglottic carcinoma is poor and has remained stable over time (1995-2009). Compared with primary radiation, primary treatment with laryngectomy does not appear to improve os.
Urban-Rural Differences in Nutritional Status and Dietary Intakes of School-Aged Children in Cambodia

This study aimed to describe the nutritional status and dietary patterns of Cambodian school-aged children compared with those in the South East Asian Nutrition Survey (SEANUTS; Indonesia, Malaysia, Thailand, and Vietnam in 2011) and to clarify the urban-rural differences using data from a nationally representative sample. The survey was conducted in 2014/2015 with a sample of 2020 children aged 6–17 years from 136 randomly selected schools. Standardized anthropometric measurements and a 1-day dietary survey by 24-h recall method were conducted. Extended analyses in the present study revealed that the difference between rural and urban areas was similar to that of the SEANUTS; the overall prevalence of stunting remained high (33.2%). Stunting was more prevalent in children living in rural areas than in those in urban areas (total: 36.4% vs. 20.4%). In contrast, the overall prevalence of overweight and obesity was not as high (3.1%), but was higher among urban children in all age groups compared with those living in rural areas (total: 6.4% vs. 2.3%). Overall, the dietary intake of children did not meet the local recommended dietary allowances, which was similar to the results of the SEANUTS and differed across urban and rural areas.
Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide-induced lung injury

Epithelial sodium channel (ENaC) provides the driving force for the removal of edema from the alveolar spaces in acute lung injury (ALI). Our previous study reported that insulin increased the expression of α‑ENaC, possibly via the serum/glucocorticoid‑inducible kinase‑1 (SGK1) pathway in ALI; however, the upstream regulator of SGK1 activity remains unclear. In the current study, C3H/HeN mice were subjected to lipopolysaccharide (LPS)‑induced lung injury without hyperglycemia. Exogenous insulin was administered intravenously using a micro‑osmotic pump, and intratracheal delivery of SGK1 small interfering RNA (siRNA) was performed. Furthermore, alveolar epithelial type II cells transfected with phosphatidylinositol 3‑kinase (PI3K) siRNA or SGK1 siRNA were incubated with insulin. Insulin protected the pulmonary epithelial barrier, reduced the apoptosis of alveolar epithelial cells, attenuated pulmonary edema, improved alveolar fluid clearance, and increased the expression levels of α‑, β‑ and γ‑ENaC in mice. In addition, in alveolar epithelial cells, insulin increased the expression levels of α‑, β‑ and γ‑ENaC, as well as the level of phosphorylated SGK1, which were then inhibited by the selective targeting of PI3K or SGK1 by siRNA. Taken together, the results of the present study demonstrated that insulin protected the lung epithelium and attenuated pulmonary edema through the upregulation of ENaC via the PI3K/SGK1 pathway in LPS‑induced lung injury.
BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer

BRG1 is one of two mutually exclusive ATPases that function as the catalytic subunit of human SWI/SNF chromatin remodeling enzymes. BRG1 has been identified as a tumor suppressor in some cancer types but has been shown to be expressed at elevated levels, relative to normal tissue, in other cancers. Using the TCGA (The Cancer Genome Atlas) prostate cancer database, we determined that BRG1 mRNA and protein expression is elevated in prostate tumors relative to normal prostate tissue. Only 3 of 491 (0.6%) sequenced tumors showed amplification of the locus or mutation in the protein coding sequence, arguing against the idea that elevated expression due to amplification or expression of a mutant BRG1 protein is associated with prostate cancer. Kaplan-Meier survival curves showed that BRG1 expression in prostate tumors inversely correlated with survival. However, BRG1 expression did not correlate with Gleason score/ISUP Grade Group, indicating it is an independent predictor of tumor progression/patient outcome. To experimentally assess BRG1 as a possible therapeutic target, we treated prostate cancer cells with a biologic inhibitor called ADAADi that targets the activity of the SNF2 family of ATPases in biochemical assays but showed specificity for BRG1 in prior tissue culture experiments. The inhibitor decreased prostate cancer cell proliferation and induced apoptosis. When directly injected into xenografts established by injection of prostate cancer cells in mouse flanks, the inhibitor decreased tumor growth and increased survival. These results indicate the efficacy of pursuing BRG1 as both an indicator of patient outcome and as a therapeutic target.
Monitoring haemodynamic response to fluid-challenge in ICU: Comparison of pressure recording analytical method and oesophageal Doppler.

BACKGROUND The ability of the pressure recording analytical method (PRAM) in tracking change in cardiac output (ΔCO) after a fluid challenge in ICU needs to be evaluated with the most contemporary comparison methods recommended by experts. OBJECTIVE Our objective was to report the trending ability of PRAM in tracking ΔCO after a fluid challenge in ICU and to compare this with oesophageal Doppler monitoring (ODM). DESIGN Prospective, observational study. SETTING Hôpital Lariboisière and Hôpital Européen George Pompidou, Paris, France, from April 2016 to December 2017. PATIENTS Critically ill patients admitted to ICU with monitoring of CO monitored by ODM and invasive arterial pressure. INTERVENTION ΔCO after fluid challenge was simultaneously registered with ODM and PRAM connected to the arterial line. MAIN OUTCOME MEASURE Polar statistics (mean angular bias, radial limits of agreement and polar concordance rate) and clinical concordance evaluation (error grid and clinical concordance rate). Predictors of bias were determined. RESULTS Sixty-eight fluid challenge were administered in 49 patients. At the time of fluid challenge, almost all were mechanically ventilated (99%), with 85% receiving norepinephrine. Admission diagnosis was septic shock in 70% of patients. Patients had a Sequential Organ Failure Assessment score of 10 [7 to 12] and a median Simplified Acute Physiology Score II of 61 [49 to 69]. Relative ΔCO bias was 7.8 (6.3°) with radial limits of agreement of ±41.7°, polar concordance rate 80% and clinical concordance rate 74%. ΔCO bias was associated with baseline bias (P = 0.007). Baseline bias was associated with radial location of the arterial line (P = 0.03). CONCLUSION When compared with ODM, PRAM has insufficient performance to track ΔCO induced by fluid challenge in ICU patients. Baseline bias is an independent predictor of trending bias. TRIAL REGISTRATION IRB 00010254-2016-033.
Interaction Between MUC1 and STAT1 Drives IFITM1 Overexpression in Aromatase Inhibitor–Resistant Breast Cancer Cells and Mediates Estrogen-Induced Apoptosis

The human oncoprotein, mucin 1 (MUC1), drives tumorigenesis in breast carcinomas by promoting epithelial-to-mesenchymal transition (EMT), epigenetic reprogramming, and evasion of immune response. MUC1 interacts with STAT1, through JAK/STAT signaling, and stimulates transcription of IFN-stimulated genes, specifically IFN-induced transmembrane protein 1 (IFITM1). Our laboratory has previously shown that IFITM1 overexpression in aromatase inhibitor (AI)-resistant breast cancer cells promotes aggressiveness. Here, we demonstrate that differential regulation of MUC1 in AI-sensitive (MCF-7 and T-47D) compared with AI-resistant (MCF-7:5C) cells is critical in mediating IFITM1 expression. A tumor microarray of 94 estrogen receptor–positive human breast tumors correlated coexpression of MUC1 and IFITM1 with poor recurrence-free survival, poor overall survival, and AI-resistance. In this study, we investigated the effects of MUC1/IFITM1 on cell survival and proliferation. We knocked down MUC1 levels with siRNA and pharmacologic inhibitors, which abrogated IFITM1 mRNA and protein expression and induced cell death in AI-resistant cells. In vivo, estrogen and ruxolitinib significantly reduced tumor size and decreased expression of MUC1, P-STAT1, and IFITM1. Implications: MUC1 and IFITM1 overexpression drives AI resistance and can be targeted with currently available therapies. Visual Overview: http://mcr.aacrjournals. org/content/molcanres/17/5/1180/F1.large. jpg. Visual Overview
Preventive Nephrology: The Role of Obesity in Different Stages of Chronic Kidney Disease

Background: Obesity is increasing worldwide and has become a nontraditional risk factor in chronic kidney disease (CKD). Summary: Obesity-related nephropathy may aggravate renal complications of the metabolic syndrome and progress to advanced CKD stages, while obesity in early stages of CKD is clearly related to the development of kidney disease. A high body mass index (BMI) in advanced CKD stages and dialysis is an advantage for survival (so called “obesity paradox”). A high lean body to fat mass index indicates a beneficial state of body composition. In contrast, loss of muscle mass with increasing fat mass causes “sarcopenia obesity,” which is related to unfavorable outcomes in renal replacement therapy. Obesity (BMI > 30–35) in renal transplant recipients is associated with a higher risk of complications such as delayed graft function, increased rates of rejection, and graft loss. While conservative management of morbid obesity is failing in most cases, bariatric surgery seems to be an option in some cases to improve renal complications in the early stage of CKD or in transplant candidates. Key Message: In conclusion, obesity is increasingly prevalent among CKD patients. Adequate management with respect to the specific role of obesity in different stages of CKD should be integrated in routine renal care.
Serological Survey of Ehrlichia canis and Anaplasma phagocytophilum in Dogs from Central Italy: An Update (2013–2017)

Ehrlichia canis and Anaplasma phagocytophilum are tick-borne bacteria of veterinary concern. Indirect immunofluorescent assay was carried out to detect antibodies against E. canis and A. phagocytophilum in 1026 owned dogs living in Central Italy during the period 2013–2017. One hundred and eighty-six (18.12%) dogs were positive for at least one pathogen and 14 (1.36%) for both agents. More in detail, 166 (16.18%) samples were positive for E. canis and 34 (3.31%) for A. phagocytophilum. No statistically significant differences in the seroprevalence values related to gender were detected, whereas the highest rate to E. canis occurred in animals aged more than 10 years. Mean seroprevalence values for both E. canis and A. phagocytophilum detected in 2014 and 2015 were statistically higher with respect to other years. Even though dogs’ owners are informed about the risk of pet infections by tick-borne pathogens and prophylaxis against ticks is often executed, E. canis and A. phagocytophilum are still present and infect the canine population in Central Italy.
Conventional audiometry, extended high-frequency audiometry, and DPOAEs in youth recreational firearm users

Abstract To determine if conventional audiometry, EHFA, and pDPOAEs are useful as early indicators of cochlear damage from recreational firearm impulse noise exposure in youth firearm users. Quantitative cross-sectional descriptive pilot study. Descriptive statistics and MANOVA with post hoc Tukey Honestly Significant Difference test were used to compare pDPOAEs (1–10 kHz), conventional audiometry (0.25–8 kHz), and EHFA (10–16 kHz) in YFUs. 25 YFUs (n = 11 7–12 years; n = 14 13–17 years) with self-reported poor compliance with hearing protector device wear. Conventional audiometric thresholds at 2-, 3- and 4 kHz were significantly poorer than normal but did not distinguish between older and younger YFUs or between the GBE and the contralateral ear. EHFA thresholds at 14- and 16 kHz were significantly poorer than for other frequencies, and differentiate between older and younger youths, but do not distinguish the GBE from the contralateral ear. Finally, pDPOAE levels were significantly reduced at 8- and 10 kHz but did not show any differences for the younger versus older YFUs or for the GBE from the contralateral ear. Conclusion: Both EHFA and pDPOAEs provide early evidence of NIHL in YFUs, and may be useful for the early detection of NIHL in YFUs.
Prevalence, Predictors, and Psychosocial Mechanism of Cancer Information Avoidance: Findings from a National Survey of U.S. Adults

ABSTRACT The current study examined the prevalence, predictors, and psychosocial mechanism of cancer information avoidance (CIA). With a nationally representative sample, we sought to confirm the prevalence of CIA among Americans. Studies, based on crisis decision theory, have shown that a lack of personal or interpersonal resources to manage threat-related information leads to information avoidance. Cancer information overload (CIO) and cancer fatalism are known predictors of CIA, and these factors were viewed as a lack of personal resources. We measured interpersonal resources by an individual’s network size. Then, to suggest a psychosocial mechanism of CIA, we tested how those personal resources interacted with interpersonal resources. A two-wave longitudinal survey was conducted using a nationally representative sample of U.S. adults (N = 795 at Wave 1 and 626 at Wave 2). Approximately, 4–5 out of 10 adults had low to high levels of CIA, and they avoided the Internet more than any other source. Items that positively predicted CIA included male gender, being non-Hispanic white, and CIO. Family and personal cancer history negatively predicted CIA. However, the positive relationship between CIO and CIA existed only for people with fewer close friends (i.e., a smaller network size). The lack of personal resources did not lead to CIA for those who had more interpersonal resources that could help them manage threat-related information. The results suggest that social support protects individuals from the emotional stress of cancer information exposure, confirming the buffering model of social support.
Brain DSC MR Perfusion in Children: A Clinical Feasibility Study Using Different Technical Standards of Contrast Administration

BACKGROUND AND PURPOSE: Dynamic susceptibility contrast MR perfusion imaging has limited results in children due to difficulties in reproducing technical standards derived from adults. This prospective, multicenter study aimed to determine DSC feasibility and quality in children using custom administration of a standard dose of gadolinium. MATERIALS AND METHODS: Eighty-three consecutive children with brain tumors underwent DSC perfusion with a standard dose of gadobutrol administered by an automated power injector. The location and size of intravenous catheters and gadobutrol volume and flow rates were reported, and local and/or systemic adverse effects were recorded. DSC was qualitatively evaluated by CBV maps and signal intensity–time curves and quantitatively by the percentage of signal drop and full width at half-maximum, and the data were compared with the standards reported for adults. Quantitative data were grouped by flow rate, and differences among groups were assessed by analysis of covariance and tested for statistical significance with a t test. RESULTS: No local or systemic adverse events were recorded independent of catheter location (63 arm, 14 hand, 6 foot), size (24–18 ga), and flow rates (1–5 mL/s). High-quality CBV maps and signal intensity–time curves were achieved in all patients, and quantitative evaluations were equal or superior to those reported for adults. No significant differences (P ≥ .05) were identified among the higher-flow-rate groups in the quantitative data. CONCLUSIONS: A custom administration of a standard dose of gadobutrol allows safe and high-quality DSC MR perfusion imaging in children.