Miracle-dz/UniFAR-FTUs huggingface dataset:
Clusters of Insomnia Disorder: An Exploratory Cluster Analysis of Objective Sleep Parameters Reveals Differences in Neurocognitive Functioning, Quantitative EEG, and Heart Rate Variability.

STUDY OBJECTIVES To empirically derive and evaluate potential clusters of Insomnia Disorder through cluster analysis from polysomnography (PSG). We hypothesized that clusters would differ on neurocognitive performance, sleep-onset measures of quantitative (q)-EEG and heart rate variability (HRV). METHODS Research volunteers with Insomnia Disorder (DSM-5) completed a neurocognitive assessment and overnight PSG measures of total sleep time (TST), wake time after sleep onset (WASO), and sleep onset latency (SOL) were used to determine clusters. RESULTS From 96 volunteers with Insomnia Disorder, cluster analysis derived at least two clusters from objective sleep parameters: Insomnia with normal objective sleep duration (I-NSD: n = 53) and Insomnia with short sleep duration (I-SSD: n = 43). At sleep onset, differences in HRV between I-NSD and I-SSD clusters suggest attenuated parasympathetic activity in I-SSD (P < 0.05). Preliminary work suggested three clusters by retaining the I-NSD and splitting the I-SSD cluster into two: I-SSD A (n = 29): defined by high WASO and I-SSD B (n = 14): a second I-SSD cluster with high SOL and medium WASO. The I-SSD B cluster performed worse than I-SSD A and I-NSD for sustained attention (P ≤ 0.05). In an exploratory analysis, q-EEG revealed reduced spectral power also in I-SSD B before (Delta, Alpha, Beta-1) and after sleep-onset (Beta-2) compared to I-SSD A and I-NSD (P ≤ 0.05). CONCLUSIONS Two insomnia clusters derived from cluster analysis differ in sleep onset HRV. Preliminary data suggest evidence for three clusters in insomnia with differences for sustained attention and sleep-onset q-EEG. CLINICAL TRIAL REGISTRATION Insomnia 100 sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR) identification number 12612000049875. URL: https://www.anzctr. org.au/Trial/Registration/TrialReview.aspx? id=347742.
Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy

Background Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus. Methods and Findings Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/−1.7) before treatment to 4.9 VAS points (SD +/−3.2) (p<0.001, CI 1.913–5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients. Conclusions The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.
Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial)

Background and Purpose— Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. Methods— According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. Results— We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60–1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). Conclusions— Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT01881152.
CHARACTERIZATION AND VITRIFICATION OF FLY ASHES FROM INCINERATION OF WASTE OF INFECTIOUS RISK CARES (WIRC)

The environmental problems of fly ashes from incineration of waste of infectious risk cares (WIRC) so called hospital waste are brought out by several researchers around the world. In the past few years, they have been concerned with problems of storage and use of these ashes. We propose glass forming as a method of storage and recovery after presenting the general characteristics of these ashes. Using X-ray diffraction and chemical analyses, it was found that the fly ashes from WIRC consisted mainly of iron chlorides. Qualitative and quantitative analyses using inductively coupled plasma and scanning electron microscopy allowed the identification of copper, zinc, lead, cadmium and other trace elements. Based on the difference in water solubility of fly ashes constituents, we have separated them into a soluble fraction in which iron chlorides are the major compounds, with a significant amount of cadmium and an insoluble fraction rich in Fe(OH)3 with a large amount of copper and zinc. The fly ash components were stabilized in a phosphate matrix by a glass forming technique. The obtained glass has a significant chemical durability which allows it to be a good candidate for the storage and trapping trace metals containing in the incinerated waste.
Transapical aortic valve replacement is a safe option in patients with poor left ventricular ejection fraction: results from the Italian Transcatheter Balloon-Expandable Registry (ITER)†

OBJECTIVES The most commonly used accesses for transcatheter aortic valve implantation (TAVI) are the transfemoral (TF-TAVI) and the transapical (TA-TAVI) ones. There are concerns about TA-TAVI use in patients with reduced left ventricular ejection fraction (LVEF). The aim of this retrospective multicentre study was to compare the outcomes of TA-TAVI and TF-TAVI in patients with poor LVEF. METHODS Patients with LVEF ≤35% were included in the analysis. Data were obtained from the Italian Transcatheter Balloon-Expandable Registry (ITER), which enrolled patients undergoing TAVI with the Sapien bioprosthesis in 33 national centres. Patients were divided into 2 groups according to the access: TA or TF. A multivariable logistic regression analysis was performed in order to evaluate whether the type of approach (TA and TF) has an impact on outcomes. RESULTS Between 2007 and 2012, 1882 patients were enrolled in the Registry. LVEF ≤35% was found in 208 (11.1%) patients. TA-TAVI and TF-TAVI were performed in 69 (33.2%) and 139 (66.8%) patients, respectively. Overall 30-day mortality was 11.6% and 7.9% in TA and TF patients, respectively (P = 0.45). Overall Kaplan-Meier survival was significantly higher in the TF-TAVI group (log rank: P = 0.003). Age [odds ratio (OR) 1.066, P = 0.016], creatinine (OR: 2.301, P < 0.001), preoperative permanent pacemaker (OR: 4.662, P = 0.035) and TA approach (OR: 2.577, P = 0.006) were identified as independent predictors of overall mortality at follow-up. However, the TA approach resulted an independent variable of mortality only 3 years after TAVI. CONCLUSIONS TAVI yields good results in patients with depressed LVEF. Age, preoperative creatinine and preoperative pacemaker are independently associated with mortality. The TA access is associated with mortality only after 3 years of follow-up, thus probably reflecting a worse general clinical status of these patients.
EFFECT OF CEMENT KILN DUST SUBSTITUTION ON CHEMICAL AND PHYSICAL PROPERTIES AND COMPRESSIVE STRENGTH OF PORTLAND AND SLAG CEMENTS

Large quantities of cement kiln dust (CKD) are produced during the manufacture of cement clinker by the dry process. The technico–economical problems that arise in the transportation of dust from the plant to outside as well as the severe pollution to the surrounding atmosphere show the utmost necessity of utilizing CKD as one of the main objectives during the last decade. CKD is produced as a solid waste from the pre-heater by-pass systems during the manufacture of Portland cement clinker, by using the dry process, as a result of the presence of some minor volatile constituents in the kiln feed and fuel. Actually, the properties of CKD depend on the kind of raw materials and the fuel used, as well as the production method or kiln type. Therefore, due to the high alkali and salt contents of the raw materials for cement production, the dry processes are normally equipped with pre-heater by-pass systems. In these systems, the circulating alkalis are removed through withdrawal of the hot gas stream along with the dust it contains.
Loss of nuclear BAP1 expression is associated with poor prognosis in oral mucosal melanoma

Oral mucosal melanoma (OMM) is an aggressive neoplasm with an extremely poor prognosis. BAP1 is a tumor suppressor that has been associated with the outcome of melanomas and other malignancies. In this study, we investigated the genetic alterations in BAP1 and the prognostic potential of BAP1 protein expression in oral mucosal melanoma. DNA sequence analysis of BAP1 from 12 OMM patient samples revealed missense mutations in the tissues from four patients. Based on immunohistochemical staining, loss of nuclear BAP1 expression was associated with poor overall survival (P < 0.001, Log-rank = 21.308) and distant metastasis (P = 0.034, OR = 0.320). Multivariate analysis showed BAP1 to be an independent prognostic factor (P = 0.027, HR = 0.479). It thus appears that loss of nuclear BAP1 expression is an independent prognostic factor of poor overall survival and associated with distant metastasis in OMM.
The Impact of a Plastic Surgeon’s Gender on Patient Choice

Abstract Background: In the patient-driven market of aesthetic surgery, an understanding of the factors that patients consider in their choice of surgeon can inform the individual plastic surgeon’s marketing strategy. Previous studies have investigated patient gender preferences for physicians in other specialties, but none has investigated whether patients consider gender when choosing a plastic surgeon. Objectives: The purpose of this study is to determine the impact of a plastic surgeon’s gender on patient choice. Methods: A prospective study was conducted in a single private practice of two plastic surgeons, one male and one female, both closely matched in training, experience, and reputation. Two hundred consecutive patients calling for a consultation were asked if they preferred a male or female doctor; their preference, age, and area(s) of interest were recorded. Results: All patients were women. Nearly half (46%) had no gender preference, 26% requested a female surgeon, and 1% requested a male. Preference for a female surgeon was significant (Binomial-test: P < 0.001). The remaining 27% requested a specific doctor, with slightly more requesting (53.7%) the male surgeon by name, than requested the female surgeon by name (46.3%), a difference that was not statistically significant (P = 0.683). Conclusions: Most female patients interested in aesthetic surgery have no gender preference. Of those who do, nearly all requested a female plastic surgeon. More important than a plastic surgeon’s gender, however, is a plastic surgeon’s reputation.
Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer

Background Genomic analysis of plasma cell-free DNA is transforming lung cancer care; however, available assays are limited by cost, turnaround time, and imperfect accuracy. Here, we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Patients and methods Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1, and other rare genotypes) were collected while on therapy and analyzed blinded to tumor genotype. Plasma NGS was carried out using enhanced tagged amplicon sequencing of hotspots and coding regions from 36 genes, as well as intronic coverage for detection of ALK/ROS1 fusions. Diagnostic accuracy was compared with plasma droplet digital PCR (ddPCR) and tumor genotype. Results A total of 168 specimens from 46 patients were studied. Matched plasma NGS and ddPCR across 120 variants from 80 samples revealed high concordance of allelic fraction (R2 = 0.95). Pretreatment, sensitivity of plasma NGS for the detection of EGFR driver mutations was 100% (30/30), compared with 87% for ddPCR (26/30). A full spectrum of rare driver oncogenic mutations could be detected including sensitive detection of ALK/ROS1 fusions (8/9 detected, 89%). Studying 25 patients positive for EGFR T790M that developed resistance to osimertinib, 15 resistance mechanisms could be detected including tertiary EGFR mutations (C797S, Q791P) and mutations or amplifications of non-EGFR genes, some of which could be detected pretreatment or months before progression. Conclusions This blinded analysis demonstrates the ability of amplicon-based plasma NGS to detect a full range of targetable genotypes in NSCLC, including fusion genes, with high accuracy. The ability of plasma NGS to detect a range of preexisting and acquired resistance mechanisms highlights its potential value as an alternative to single mutation digital PCR-based plasma assays for personalizing treatment of TKI resistance in lung cancer.
Measurements of mouse pulmonary artery biomechanics.

BACKGROUND Robust techniques for characterizing the biomechanical properties of mouse pulmonary arteries will permit exciting gene-level hypotheses regarding pulmonary vascular disease to be tested in genetically engineered animals. In this paper, we present the first measurements of the biomechanical properties of mouse pulmonary arteries. METHOD OF APPROACH In an isolated vessel perfusion system, transmural pressure, internal diameter and wall thickness were measured during inflation and deflation of mouse pulmonary arteries over low (5-40 mmHg) and high (10-120 mmHg) pressure ranges representing physiological pressures in the pulmonary and systemic circulations, respectively. RESULTS During inflation, circumferential stress versus strain showed the nonlinear "J"-shape typical of arteries. Hudetz's incremental elastic modulus ranged from 27 +/- 13 kPa (n = 7) during low-pressure inflation to 2,700 +/- 1,700 kPa (n = 9) during high-pressure inflation. The low and high-pressure testing protocols yielded quantitatively indistinguishable stress-strain and modulus-strain results. Histology performed to assess the state of the tissue after mechanical testing showed intact medial and adventitial architecture with some loss of endothelium, suggesting that smooth muscle cell contractile strength could also be measured with these techniques. CONCLUSIONS The measurement techniques described demonstrate the feasibility of quantifying mouse pulmonary artery biomechanical properties. Stress-strain behavior and incremental modulus values are presented for normal, healthy arteries over a wide pressure range. These techniques will be useful for investigations into biomechanical abnormalities in pulmonary vascular disease.
fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease

Objective: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer’s disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. Methods: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer’s disease were studied using fMRI during a face–name association encoding task. The fMRI paradigm used a block design with three conditions: novel face–name pairs, repeated face–name pairs, and visual fixation. Results: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face–name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. Conclusions: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer’s disease compared with normal aging.
Outcomes of persistent and long-standing persistent atrial fibrillation ablation: a systematic review and meta-analysis.

Aims Several techniques have been utilized for the ablation of persistent (P) and long-standing persistent (LsP) atrial fibrillation (AF); however, the best approach of substrate ablation remains poorly defined. This study aims to examine the impact of ablation approach on outcomes associated with P or LsP AF ablation by conducting a meta-analysis and regression on contemporary literature. Methods and results A systematic literature review was conducted up to 29 July 2015 for scientific literature reporting on outcomes associated with P or LsP AF ablation. One hundred and thirteen studies reported outcomes in a total of 18 657 patients undergoing various ablation approaches for the treatment of P-LsP AF between 2001 and 2015. The point efficacy estimate of a single-AF ablation procedure without the use of anti-arrhythmic drugs was 43% (95% CI; 39-47%). Multiple procedures and/or the use of anti-arrhythmic drugs increase success to 69% (95% CI; 66-71%). Meta-regression revealed that ablation technique (P < 0.001) and left atrial size (P = 0.02) were predictive of single procedure, drug-free success. The addition of extra-pulmonary substrate approaches was associated with declining efficacy when compared to a pulmonary vein ablation alone. Conclusion The efficacy of a single-AF ablation procedure for P or LsP AF is 43%; however, can be increased to 69% with the use of multiple procedures and/or anti-arrhythmic drugs. Current literature supports the finding that pulmonary vein antrum ablation/isolation is at least equivalently efficacious to other contemporary P-LsP ablation strategies.
Cognitive impairment and intracranial atherosclerotic stenosis in general population

Objective To investigate the association between asymptomatic intracranial atherosclerosis and cognitive impairment in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods ARIC participants underwent high-resolution 3T magnetic resonance angiography and a neuropsychology battery and neurologic examination adjudicated by an expert panel to detect mild cognitive impairment (MCI) and dementia. We adjusted for demographic and vascular risk factors in weighted logistic regression analysis, accounting for stratified sampling design and attrition, to determine the association of intracranial atherosclerotic stenosis (ICAS) with cognitive impairment. Results In 1,701 participants (mean age 76 ± 5.3, 41% men, 71% whites, 29% blacks) with adequate imaging quality and no history of stroke, MCI was identified in 578 (34%) and dementia in 79 (4.6%). In white participants, after adjustment for demographic and vascular risk factors, ICAS ≥50% (vs no ICAS) was strongly associated with dementia (odds ratio [OR] 4.1, 95% confidence interval [CI] 1.7–10.0) and with any cognitive impairment (OR 1.7, 95% CI 1.1–2.8). In contrast, no association was found between ICAS ≥50% and MCI or dementia in blacks, although the sample size was limited and estimates were imprecise. Conclusion Our results suggest that asymptomatic ICAS is independently associated with cognitive impairment and dementia in whites.
A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma

Abstract Background There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3–12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial Registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703