Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of working hours on sleep and mental health.

Background The number of hours people are required to work has a pervasive influence on both physical and mental health. Excessive working hours can also negatively affect sleep quality. The impact at work of mental health problems can have serious consequences for individuals' as well as for organizations' productivity. Aims To evaluate differences in sleep quality and anxiety and depression symptoms between longer working hours group (LWHG) and regular working hours group (RWHG). To examine factors influencing weekly working hours, sleep quality and anxiety and depressive symptoms. Methods Participants were divided into two groups, RWHG and LWHG, based on working hours, with a cut-off of 48 h per week. We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression symptoms and the Pittsburgh Sleep Quality Index (PSQI) to measure the quality and patterns of sleep. Results The response rate was 23%. Among the 429 study participants, those in the LWHG group (n = 256, 53%) had significantly more depressive and anxiety symptoms and worse sleep quality than those in RWHG (n = 223, 47%). Working time was significantly positively correlated with higher corporate position and HADS scores. Moreover, HADS scores were positively correlated with PSQI scores and negatively correlated with age. Conclusions This study suggests that longer working hours are associated with poorer mental health status and increasing levels of anxiety and depression symptoms. There was a positive correlation between these symptoms and sleep disturbances.
The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.
Effects of Kinect-based virtual reality game training on upper extremity motor recovery in chronic stroke

Abstract Background: Therapeutic benefits of Kinect-based virtual reality (VR) game training in rehabilitation encourage its use to improve motor function. Objective: To assess the effects of Kinect-based VR training on motor recovery of the upper extremity and functional outcomes in patients with chronic stroke. Methods: In this randomized controlled trial, group A received 20 sessions of physical therapy (PT) + 20 sessions of Kinect-based VR training and group B received only 20 sessions of PT. Clinical outcome measures were assessed at baseline and at the end of the treatments. Primary outcome measures that assess stroke patients’ motor function included upper extremity (UE) Fugl-Meyer Assessment (FMA). Secondary outcome measures were Brunnstrom Recovery Stages (BRS), Modified Ashworth Scale (MAS), Box and Block test (BBT), Motricity index (MI), and active range of motion (AROM) measurement. Results: Statistically significant improvements in game scores (p < 0.05) were observed in group A. In within-group analysis, there were statistically significant improvements in all clinical outcome measures except for the BRS-hand, MAS-distal, and MAS-hand in group A; MAS-(proximal, distal, hand) and BRS-(UE, hand) in group B compared with baseline values. Differences from baseline of FMA, MI, and AROM (except adduction of shoulder and extension of elbow) were greater in group A (p < 0.05). Conclusions: To conclude, our results suggest that the adjunct use of Kinect-based VR training may contribute to the improvement of UE motor function and AROM in chronic stroke patients. Further studies with a larger number of subjects with longer follow-up periods are needed to establish its effectiveness in neurorehabilitation.
Inactivation of γ‐secretases leads to accumulation of substrates and non‐Alzheimer neurodegeneration

γ‐Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ‐secretases in the pyramidal neurons of the postnatal forebrain by deleting the three anterior pharynx defective 1 (Aph1) subunits (Aph1abc cKO Cre+). The mice show progressive cortical atrophy, neuronal loss, and gliosis. Interestingly, this is associated with more than 10‐fold accumulation of membrane‐bound fragments of App, Aplp1, Nrg1, and Dcc, while other known substrates of γ‐secretase such as Aplp2, Lrp1, and Sdc3 accumulate to lesser extents. Despite numerous reports linking neurodegeneration to accumulation of membrane‐bound App fragments, deletion of App expression in the combined Aph1 knockout does not rescue this phenotype. Importantly, knockout of only Aph1a‐ or Aph1bc‐secretases causes limited and differential accumulation of substrates. This was not associated with neurodegeneration. Further development of selective Aph1‐γ‐secretase inhibitors should be considered for treatment of Alzheimer's disease.
The Association Between Musculoskeletal Pain and Circulating Ornithine: A Population-Based Study

Objective Based on several previous clinical studies, we hypothesized that ornithine levels are different among subjects with persistent musculoskeletal pain compared with other subjects in the population. Design The study sample consisted of 221 adults with nonpersistent pain, 76 with persistent pain, and 61 with no pain. Concentrations of glutamic acid, ornithine, citrulline, arginine, proline, and spermidine were analyzed using a mass spectrometer. Setting Lapinlahti municipality in Finland. Results For the subjects with no pain, nonpersistent pain, and persistent pain, the ornithine concentrations for men were 85.3 µmol/L (SD = 28.9 µmol/L), 98.9 µmol/L (SD = 37.8 µmol/L), and 102.1 µmol/L (SD = 37.1 µmol/L; P = 0.033), respectively. The corresponding concentrations for women were 82.8 µmol/L (SD = 25.2 µmol/L), 83.7 µmol/L (SD = 27.8 µmol/L), and 103.2 µmol/L (SD = 34.9 µmol/L; P = 0.0031). There were no significant differences between the pain groups for any of the other investigated amino acids. Relative sex-specific ornithine concentration adjusted for age, glomerular filtration rate, smoking, body mass index, physical activity, and depressive symptoms was associated with pain ( P = 0.025), the ornithine level being higher in the persistent pain group than in the no pain ( P = 0.006) and nonpersistent pain ( P = 0.032) groups. Conclusion Ornithine levels are elevated in general population subjects with persistent pain.
Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research.
A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat

A soft, skin-mounted microfluidic device captures microliter volumes of sweat and quantitatively measures biochemical markers by colorimetric analysis. Better health? Prepare to sweat Wearable technology is a popular way many people monitor their general health and fitness, tracking heart rate, calories, and steps. Koh et al. now take wearable technology one step further. They have developed and tested a flexible microfluidic device that adheres to human skin. This device collects and analyzes sweat during exercise. Using colorimetric biochemical assays and integrating smartphone image capture analysis, the device detected lactate, glucose, and chloride ion concentrations in sweat as well as sweat pH while stuck to the skin of individuals during a controlled cycling test. Colorimetric readouts showed comparable results to conventional analyses, and the sweat patches remained intact and functional even when used during an outdoor endurance bicycle race. The authors suggest that microfluidic devices could be used during athletic or military training and could be adapted to test other bodily fluids such as tears or saliva. Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate.
Metastability and avalanche dynamics in strongly correlated gases with long-range interactions

Significance Most structured matter, whether in the form of solids or macromolecules, is found in metastable states. Metastability, as well as the transition processes between metastable states, is ubiquitous in nature, but challenges our tools to describe such complex quantum systems. Using a quantum gas, we assemble a synthetic quantum many-body system featuring metastability. The essential ingredient is a global interaction that couples superfluid shells of the system with a metastable Mott insulator in its core. We study in real time the self-induced switching of the core to a different density configuration, a process reminiscent of the folding between discrete structures encountered in the study of macromolecules. We experimentally study the stability of a bosonic Mott insulator against the formation of a density wave induced by long-range interactions and characterize the intrinsic dynamics between these two states. The Mott insulator is created in a quantum degenerate gas of 87-Rubidium atoms, trapped in a 3D optical lattice. The gas is located inside and globally coupled to an optical cavity. This causes interactions of global range, mediated by photons dispersively scattered between a transverse lattice and the cavity. The scattering comes with an atomic density modulation, which is measured by the photon flux leaking from the cavity. We initialize the system in a Mott-insulating state and then rapidly increase the global coupling strength. We observe that the system falls into either of two distinct final states. One is characterized by a low photon flux, signaling a Mott insulator, and the other is characterized by a high photon flux, which we associate with a density wave. Ramping the global coupling slowly, we observe a hysteresis loop between the two states—a further signature of metastability. A comparison with a theoretical model confirms that the metastability originates in the competition between short- and global-range interactions. From the increasing photon flux monitored during the switching process, we find that several thousand atoms tunnel to a neighboring site on the timescale of the single-particle dynamics. We argue that a density modulation, initially forming in the compressible surface of the trapped gas, triggers an avalanche tunneling process in the Mott-insulating region.
Targeting Tumor Vasculature with TNF Leads Effector T Cells to the Tumor and Enhances Therapeutic Efficacy of Immune Checkpoint Blockers in Combination with Adoptive Cell Therapy

Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intratumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors. Experimental Design: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with autochthonous prostate cancer and C57BL/6 mice with orthotopic B16 melanoma were treated with NGR-TNF, adoptive T-cell therapy (ACT), and ICB, and monitored for immune surveillance and disease progression. Results: The combination of ACT, NGR-TNF, and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma. Mechanistically, the therapeutic effects were associated with potent tumor infiltration, especially by endogenous but also by adoptively transferred PD-1+, granzyme B+, and interferon-γ+ CTLs. The therapeutic effects were also associated with favorable T-effector/regulatory T cell ratios. Conclusions: Targeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. Clin Cancer Res; 24(9); 2171–81. ©2018 AACR.
Diabetes Care Practices in Primary Care: Results from Two Samples and Three Measurement Sets

PURPOSE here has been substantial recent interest in diabetes disease management interventions, guidelines, and care practices. As the vast majority of diabetes care occurs in primary care settings, it makes sense to evaluate current levels of recommended practices in different primary care settings. METHODS We report on two separate studies that included a combined total of 389 patients seen by over 30 different providers. Three different sets of recommended practices were assessed: (1) the ADA provider recognition measures, (2) the proposed Diabetes Quality Improvement Project measures, and (3) the state of Oregon Population-Based Guidelines for Diabetes. RESULTS In general, there was only a moderate level of adherence to recommended practices, and adherence was much lower for behavioral or patient-focused practices as contrasted with laboratory tests. There was considerable variability across providers and across different guidelines activities. CONCLUSIONS Policy and quality improvement implications and future research issues are discussed, including the need for studying different measurement approaches for evaluating guidelines adherence.
Neuropathological Staging of Brain Pathology in Sporadic Parkinson’s disease: Separating the Wheat from the Chaff

A relatively small number of especially susceptible nerve cell types within multiple neurotransmitter systems of the human central, peripheral, and enteric nervous systems (CNS, PNS, ENS) become involved in the degenerative process underlying sporadic Parkinson’s disease (sPD). The six-stage model we proposed for brain pathology related to sPD (Neurobiol Aging 2003) was a retrospective study of incidental and clinically diagnosed cases performed on unconventionally thick tissue sections (100 μm) from a large number of brain regions.The staging model emphasized what we perceived to be a sequential development of increasing degrees of Lewy pathology in anatomically interconnected regions together with the loss of aminergic projection neurons in, but not limited to, the locus coeruleus and substantia nigra. The same weight was assigned to axonal and somatodendritic Lewy pathology, and the olfactory bulb was included for the first time in a sPD staging system. After years of research, it now appears that the earliest lesions could develop at nonnigral (dopamine agonist nonresponsive) sites, where the surrounding environment is potentially hostile: the olfactory bulb and, possibly, the ENS. The current lack of knowledge regarding the development of Lewy pathology within the peripheral autonomic nervous system, however, means that alternative extra-CNS sites of origin cannot be disregarded as possible candidates. The PD staging system not only caused controversy but contributed a framework for (1) assessing pathology in the spinal cord, ENS, and PNS in relationship to that evolving in the brain, (2) defining prodromal disease and cohorts of at-risk individuals, (3) developing potential prognostic biomarkers for very early disease, (4) testing novel hypotheses and experimental models of α-synuclein propagation and disease progression, and (5) finding causally-oriented therapies that intervene before the substantia nigra becomes involved. The identification of new disease mechanisms at the molecular and cellular levels indicates that physical contacts (transsynaptic) and transneuronal transmission between vulnerable nerve cells are somehow crucial to the pathogenesis of sPD.
Survival Benefit of Adjuvant Radiotherapy: An Analysis of Low-Stage Invasive Ovarian Mucinous Carcinomas

Objective Our aim was to evaluate the population-based outcomes of stages I and II invasive ovarian mucinous carcinomas (MCs) treated with adjuvant platinum-based chemotherapy and abdominopelvic radiotherapy (XRT). Methods International Federation of Gynecology and Obstetrics stage I/II MC cases referred to the British Columbia Cancer Agency between 1984 and 2014 were reviewed. Chemotherapy (minimum of 3 cycles) and XRT were the institutional policy for stages IA/B (grade 2/3) and IC/II (any grade). Physician patterns of practice determined XRT use in eligible patients, allowing for the comparison of outcomes based on receipt of XRT treatment on disease-free survival (DFS) and overall survival (OS). Results We identified 129 patients. Univariate analyses on substages IA, IC no rupture, IC with intraoperative rupture, and IC with preoperative rupture demonstrated 10-year DFS rates of 67%, 67%, 67%, and 27% (P = 0.004), respectively, and OS rates of 72%, 72%, 67%, and 38% (P = 0.01), respectively. For all patients, adjuvant XRT demonstrated improved 10-year DFS (78% vs 36%, P = 0.05) and OS (83% vs 36%, P = 0.02). Subgroup analysis did not detect a benefit of adjuvant therapy for stage IA grade 1/2. Multivariate analysis confirmed the benefit of XRT on DFS (hazard ratio, 0.14; 95% confidence interval, 0.02–0.98; P = 0.047) and a trend to improved OS (hazard ratio, 0.12; 95% confidence interval, 0.009–1.64; P = 0.11), whereas decision tree analysis demonstrated a reduced rate of relapse (33% vs 77%) and death (20% vs 46%) with the use of XRT, exclusive of patients with preoperative rupture. Conclusions This population-based retrospective study is the first to demonstrate that the use of adjuvant abdominopelvic XRT after chemotherapy can improve survival in patients diagnosed as having stage I/II MC. Patients with stage IA grade 1 and grade 2 MC can have adjuvant therapy omitted.
Load-Velocity Relationship in Variations of the Half-Squat Exercise: Influence of Execution Technique.

Pérez-Castilla, A, García-Ramos, A, Padial, P, Morales-Artacho, AJ, and Feriche, B. Load-velocity relationship in variations of the half-squat exercise: influence of execution technique. J Strength Cond Res XX(X): 000-000, 2017-Previous studies have revealed that the velocity of the bar can be used to determine the intensity of different resistance training exercises. However, the load-velocity relationship seems to be exercise dependent. This study aimed to compare the load-velocity relationship obtained from 2 variations of the half-squat exercise (traditional vs. ballistic) using 2 execution techniques (eccentric-concentric vs. concentric-only). Twenty men performed a submaximal progressive loading test in 4 half-squat exercises: eccentric-concentric traditional-squat, concentric-only traditional-squat, countermovement jump (i.e., ballistic squat using the eccentric-concentric technique), and squat jump (i.e., ballistic squat using the concentric-only technique). Individual linear regressions were used to estimate the 1 repetition maximum (1RM) for each half-squat exercise. Thereafter, another linear regression was applied to establish the relationship between the relative load (%RM) and mean propulsive velocity (MPV). For all exercises, a strong relationship was observed between %RM and MPV: eccentric-concentric traditional-squat (R = 0.949), concentric-only traditional-squat (R = 0.920), countermovement jump (R = 0.957), and squat jump (R = 0.879). The velocities associated with each %RM were higher for the ballistic variation and the eccentric-concentric technique than for the traditional variation and concentric-only technique, respectively. Differences in velocity among the half-squat exercises decreased with the increment in the relative load. These results demonstrate that the MPV can be used to predict exercise intensity in the 4 half-squat exercises. However, independent regressions are required for each half-squat exercise because the load-velocity relationship proved to be task specific.