Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventable premature deaths (PYLL) in Northern Dimension partnership countries 2003-13.

Background Objective was to measure preventable premature loss of life in countries from same geographical area but with considerable differences in social and economic development. By comparing inter-country differences and similarities in premature mortality, acceleration of health-in-all-policies is enhanced. Methods Preventable premature deaths were described by Potential Years of Life Lost (PYLL). Data consisted of death registers for 2003, 2009 and 2013. PYLL-rates were age-standardized by using standard OECD population from 1980 and expressed as sum of lost life years per 100 000 citizens. Results In Northern Dimension area, PYLL-rates had declined from 2003 to 2013. In 2013, worst PYLL-rate was in Belarus 9851 and best in Sweden 2511. PYLL-rates among men were twice as high as among women. Most premature losses (1023) were due to external causes. Malignant neoplasms came second (921) and vascular diseases third (816). Alcohol was also an important cause (270) and country differences were over 10-fold. Conclusions In ND-area, the overall development of public health has been good during 2003-13. Nevertheless, for all countries foci for public health improvement and learning from each other could be identified. Examining the health of populations in countries from relatively similar geographical area with different social history and cultures can provide them with evidence-based tools for health-in-all-policies to advocate health promotion and disease prevention. Gender differences due to preventable premature deaths are striking. The higher the national PYLL-rate, the bigger the PYLL-rate difference between men and women and the loss of human capital.
Hyperbaric oxygen treatment of fibromyalgia: a prospective observational clinical study.

OBJECTIVES Fibromyalgia (FM) is a syndrome of unknown aetiology that is characterised by widespread musculoskeletal pain, fatigue and disordered sleep, and often associated with neuropsychiatric and cognitive symptoms. Current treatment options are only partially effective, but hyperbaric oxygen therapy (HBOT) seems to be capable of relieving some of the symptoms. The aim of this study was to evaluate the efficacy and safety of HBOT after fewer sessions than generally used, chosen on the basis of pre-clinical and clinical data showing its rapid and sustained antinociceptive effect. METHODS Patients with FM underwent HBOT (100% oxygen at 2.5 ata with air breaks) administered on three days per week for a total of twenty 90-minute sessions. Pain, fatigue, the quality of sleep, symptoms of anxiety and depression, and the patients' health-related quality of life were prospectively assessed before and after ten and twenty sessions. RESULTS Twenty-eight of the 32 study patients completed the 20 HBOT sessions. Pain scores and the symptoms of anxiety (but not those of depression) significantly improved after both 10 and 20 sessions, whereas fatigue and FM symptom severity scores significantly improved only after 20 sessions. There was no significant change in the quality of sleep. The adverse effects were limited. CONCLUSIONS These findings support the view that HBOT is an effective, rapid and safe means of treating various symptoms of FM.
Drainage versus No Drainage after Laparoscopic Cholecystectomy for Acute Cholecystitis: A Meta-Analysis

To conduct a randomized controlled trial (RCT), meta-analysis to assess the effectiveness of drains in reducing complications after laparoscopic cholecystectomy (LC) for acute cholecystitis needs to be carried out. An electronic search of PubMed, Embase, Science Citation Index, and the Cochrane Library from January 1990 to January 2018 was performed to identify randomized clinical trials that compare prophylactic drainage with no drainage in LC for acute cholecystitis. The outcomes were calculated as odds ratios (ORs) with 95 per cent confidence intervals (CIs) using RevMan 5.2. Four RCTs, which included 796 patients, were identified for analysis in our study. There was no statistically significant difference in the rate of morbidities (OR = 1.23, 95% CI 0.55–2.76, P = 0.61). Abdominal pain was more severe in the drain group 24 hours after surgery (mean difference = 0.80, 95% CI 0.47–1.14; P < 0.00001). No significant difference was present with respect to wound infection rate and hospital stay. The use of abdominal drainage does not appear to be of any benefit in patients having undergone early LC for acute cholecystitis.
Interactive Contexts Increase Informativeness in Children’s Referential Communication

Adults adjust the informativeness of their utterances to the needs of their addressee. For children, however, relevant evidence is mixed. In this article we explore the communicative circumstances under which children offer informative descriptions. In Experiment 1, 4- and 5-year-old children and adults described a target event from a pair of almost identical events to a passive confederate listener who could either see or not see the referents. Adults provided disambiguating information that picked out the target event but children massively failed to do so (even though 5-year-olds were more informative than 4-year-olds). Furthermore, both children and adults were more likely to mention atypical than typical disambiguating event components. Because of the contrastive nature of the task, the listener’s visual access had no effects on production. Experiment 2 was a more interactive version of Experiment 1 where participants played a guessing game with a “naïve” listener. In this context, children (and adults) became overall more informative, and the difference between child groups disappeared. We conclude that the informativeness of children’s event descriptions is heavily context-dependent and is boosted when children engage in a collaborative interaction with a “true” interlocutor.
Changes in physical and mental health are associated with cardiovascular disease incidence in postmenopausal women.

BACKGROUND physical and mental health are important risk factors for cardiovascular disease (CVD) incidence and death among postmenopausal women. The objective of this study was to assess whether changes in physical and mental health were associated with CVD incidence and death. METHODS in the Women's Health Initiative Observational Study, 48,906 women (50-79 years) had complete data at baseline on physical and mental health (assessed with Short Form-36) and key covariates. Changes in self-reported physical and mental health were calculated between baseline and year 3. Incident CVD and death between year 3 and end of the study were verified with medical records. RESULTS over a median 8.2-year follow-up, 2,319 women developed CVD, and 1,571 women died, including 361 CVD deaths. Women with continued poor health and those with worsened health had significantly increased risk of CVD incidence, CVD-specific death and all-cause death relative to women with continued good health. Both major and minor declines in physical health were associated with an increased risk of these outcomes relative to women with no change in physical health. Only major declines in mental health were associated with poor prognosis. CONCLUSIONS changes in physical and mental health over 3 years were independently associated with subsequent CVD events.
Opportunities and Issues in Modeling Intensive Longitudinal Data: Learning from the COGITO Project

Abstract Technological developments increasingly permit the collection of longitudinal data sets in which the data structure contains a large number of participants N and a large number of measurement occasions T. Promising new dynamical systems approaches to the analysis of large N, large T data sets have been proposed that utilize both between-subjects and within-subjects information. The COGITO project, begun over a decade ago, is an early large N = 204, large T = 100 study that collected high quality cognitive and psychosocial data. In this introduction, I describe the COGITO project and conceptual and statistical issues that arise in the analysis of large N, large T data sets. I provide a brief overview of the five papers in the special section which include conceptual pieces, a didactic presentation of a dynamic structural equation approach, and papers reporting new statistical analyses of the COGITO data set to answer substantive questions. Although many challenges remain, these new approaches offer the promise of improving scientific inquiry in the behavioral sciences.
Open-Boundary Molecular Mechanics/Coarse-Grained Framework for Simulations of Low-Resolution G-Protein-Coupled Receptor–Ligand Complexes

G-protein-coupled receptors (GPCRs) constitute as much as 30% of the overall proteins targeted by FDA-approved drugs. However, paucity of structural experimental information and low sequence identity between members of the family impair the reliability of traditional docking approaches and atomistic molecular dynamics simulations for in silico pharmacological applications. We present here a dual-resolution approach tailored for such low-resolution models. It couples a hybrid molecular mechanics/coarse-grained (MM/CG) scheme, previously developed by us for GPCR–ligand complexes, with a Hamiltonian-based adaptive resolution scheme (H-AdResS) for the solvent. This dual-resolution approach removes potentially inaccurate atomistic details from the model while building a rigorous statistical ensemble—the grand canonical one—in the high-resolution region. We validate the method on a well-studied GPCR–ligand complex, for which the 3D structure is known, against atomistic simulations. This implementation paves the way for future accurate in silico studies of low-resolution ligand/GPCRs models.
CAF-Secreted Annexin A1 Induces Prostate Cancer Cells to Gain Stem Cell–like Features

Annexin A1 (AnxA1), a phospholipid-binding protein and regulator of glucocorticoid-induced inflammatory signaling, has implications in cancer. Here, a role for AnxA1 in prostate adenocarcinoma was determined using primary cultures and a tumor cell line (cE1), all derived from the conditional Pten deletion mouse model of prostate cancer. AnxA1 secretion by prostate-derived cancer-associated fibroblasts (CAF) was significantly higher than by normal prostate fibroblasts (NPF). Prostate tumor cells were sorted to enrich for epithelial subpopulations based on nonhematopoietic lineage, high SCA-1, and high or medium levels of CD49f. Compared with controls, AnxA1 enhanced stem cell–like properties in high- and medium-expression subpopulations of sorted cE1 and primary cells, in vitro, through formation of greater number of spheroids with increased complexity, and in vivo, through generation of more, larger, and histologically complex glandular structures, along with increased expression of p63, a basal/progenitor marker. The differentiated medium-expression subpopulations from cE1 and primary cells were most susceptible to gain stem cell–like properties as shown by increased spheroid and glandular formation. Further supporting this increased plasticity, AnxA1 was shown to regulate epithelial-to-mesenchymal transition in cE1 cells. These results suggest that CAF-secreted AnxA1 contributes to tumor stem cell dynamics via two separate but complementary pathways: induction of a dedifferentiation process leading to generation of stem-like cells from a subpopulation of cancer epithelial cells and stimulation of proliferation and differentiation of the cancer stem-like cells. Implications: AnxA1 participates in a paradigm in which malignant prostate epithelial cells that are not cancer stem cells are induced to gain cancer stem cell–like properties. Mol Cancer Res; 12(4); 607–21. ©2014 AACR.
Improved Morphine-Loaded Hydrogels for Wound-Related Pain Relief

The use of morphine applied topically to painful wounds has potential advantages, such as dose reduction, fewer side effects and compound formulations, have been proposed for this purpose. Given the potential high impact of drug product quality on a patient’s health, the aim of the present study was to develop two stable sterile hydrogels containing morphine hydrochloride, intended for topical application on painful wounds. Two carboxymethylcellulose sodium-based hydrogels were prepared containing 0.125% w/w (F1-MH semi-solid formulation) and 1.0% w/w (F2-MH fluid formulation) morphine hydrochloride (MH), respectively. Studies included a risk assessment approach for definition of the quality target product profile (QTPP) and assessment of critical quality attributes (CQA) of the hydrogels to support product quality and safety. Safe, odourless, yellowish, translucent and homogeneous gels were obtained, with suitable microbiological and pharmaceutical characteristics. The active substance concentration was adapted according to the characteristics of the dose-metering device. Release profiles were investigated using Franz diffusion cells, and characterised by different kinetic models. Increasing gel viscosity prolonged drug release, with rates of 17.9 ± 2.2 μg·cm−2·h−1 (F1-MH) and 258.0 ± 30.4 μg·cm−2·h−1 (F2-MH), allowing for the reduction of the number of applications and improving patient compliance. The gels proved to be stable for up to 60 days at room temperature. The semi-solid and fluid MH-containing hydrogel formulations are safe, stable and suitable for use in hospital settings, which is rather important for wound-related pain management in cancer palliative care or burn patients.
Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering.

RATIONALE Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts. OBJECTIVES To define a scalable cell culture system to deliver airway epithelium to clinical grafts. METHODS Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures. MEASUREMENTS AND MAIN RESULTS 3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model. CONCLUSIONS Our method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.
Efficacy of Combined General, Special, and Specific Resistance Training on Pace Bowling Skill in Club-Standard Cricketers.

Feros, SA, Young, WB, and O'Brien, BJ. Efficacy of combined general, special, and specific resistance training on pace bowling skill in club-standard cricketers. J Strength Cond Res XX(X): 000-000, 2018-This study investigated the efficacy of combined "general," "special," and "specific" resistance training on pace bowling skill. Twelve male, club-standard pace bowlers were randomly allocated to a combined resistance training (CRT) program or traditional cricket training (TCT) program for 8 weeks. The CRT group (n = 6) trained with 300, 250-g, and standard cricket balls; performed 20-m sprints with +20% and +15% body mass resistance (but also unresisted); and completed chin-up and pull-up training. The TCT group (n = 6) trained with standard balls and performed unresisted 20-m sprints. No statistically significant GROUP × TIME interactions were identified. The CRT group demonstrated a "clear moderate" enhancement in peak ball release speed (mean ±95% confidence limits [CLs]: 1.2 ± 1.5 m·s, d = 0.66 ± 0.83), a "clear large" increase in mean radial error (mean ±95% CLs: 7.1 ± 6.5 cm, d = 0.94 ± 0.87), and a "clear large" rise in bivariate variable error (mean ±95% CLs: 7.2 ± 7.8 cm, d = 0.97 ± 1.05). The TCT group exhibited "unclear" changes across all pace bowling skill measures. Both groups displayed "unclear" changes in approach speed, 20-m sprint time, and 1 repetition maximum pull-up strength. In 8 weeks, the CRT program improved peak ball release speed, but at the cost of poorer bowling accuracy and consistency of bowling accuracy. These findings could be attributed to bowling with the heavier balls. The inclusion of "specific" resistance training does not seem to be effective in enhancing all-round pace bowling skill in club-standard cricketers.
Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential

Abstract The study aims to evaluate the antiprotozoal activities of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Compounds 1–20 were obtained and identified by using chromatographic and spectroscopic techniques. The antiparasitic assays were performed on the intracellular form of T. cruzi and L. amazonensis using human leukaemic THP-1 cells as the host. The mechanism of action of the most active compounds was explored in silico by molecular docking using T. cruzi trypanothione reductase (TR) as a target, whereas the in vitro studies were performed by enzymatic assay using T. cruzi recombinant TR. In addition, the mitochondrial membrane potential was evaluated by flow cytometry. Two flavonoids, one triterpene and three acetogenins showed from high to moderate trypanocidal activities with IC50 values ranging 3.6–37.2 µm while three of the metabolites were moderately leishmanicidal. The molecular docking study revealed interactions between TR and the most trypanocidal compounds 1 (abyssinone IV) and 2 (atalantoflavone). In contrast, both showed no effect on TR in vitro. For the mitochondrial membrane potential assay, atalantoflavone (2) displayed a dose-dependent depolarization. On the basis of the aforementioned results, this compound's structure could be chemically explored in order to develop more potent trypanocidal derivatives.
Validating Rheumatoid Arthritis Remission Using the Patients’ Perspective: Results from a Special Interest Group at OMERACT 2016

Objective. The Outcome Measures in Rheumatology (OMERACT) working group on the patients’ perspective on remission in rheumatoid arthritis (RA) has been working on this topic since 2010. At OMERACT 2016, progress and preliminary data on validity of measurement instruments for pain, fatigue, and independence in remission in RA were presented, and future directions were explored. Methods. A special interest group was organized, in which the current data on the patients’ perspective on remission were presented. The ongoing study that aimed to validate measurement instruments for pain, fatigue, and independence in a state of low disease activity or remission was presented, and preliminary data on construct validity and discriminative capacity were evaluated cross-sectionally. Results. At OMERACT 2016, the progress of the working group and preliminary data from 142 of the anticipated 300 patients were presented. Selected instruments significantly correlated with the Disease Activity Score in 28 joints (construct validity) and all instruments except 1 discriminated between patients in and patients not in remission. The subsequent discussion mainly focused around 3 points: (1) the formulation of patient perceived remission, (2) the duration of remission, and (3) the measurement of the domain independence. An informal vote indicated a slight preference for working toward modifying the current remission criteria by adding patient-reported outcomes (PRO), or by substituting the patient’s global assessment with 1 or more PRO. Conclusion. More evidence on measuring patients’ perspective on remission in RA is needed before an informed decision can be made regarding development or modification of remission definitions.
Dynamic functional nucleus is a potential biomarker for structural degeneration in cervical spine discs

If intervertebral disc degeneration can be identified early, preventative treatments may be initiated before symptoms become disabling and costly. Changes in disc mechanics, such as the decrease in the compressive modulus of the nucleus, are some of the earliest signs of degeneration. Therefore, in vivo changes in the disc response to compressive load may serve as a biomarker for pending or early disc degeneration. The aim of this study was to assess the potential for using in vivo dynamic disc deformation to identify pathologic structural degeneration of the intervertebral disc. A validated model‐based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion/extension and axial rotation of the cervical spine. A computational model of the subaxial intervertebral discs was developed to identify the dynamic functional nucleus of each disc, that is, the disc region that underwent little to no additional compression during dynamic movements. The size and location of the dynamic functional nucleus was determined for 10 C5/C6 spondylosis patients, 10 C5/C6/C7 spondylosis patients, and 10 asymptomatic controls. The dynamic functional nucleus size was sensitive (significantly smaller than controls in 5 of 6 measurements at the diseased disc) and specific (no difference from controls in 9 of 10 measurements at non‐diseased discs) to pathologic disc degeneration. These results provide evidence to suggest that structural disc degeneration, manifested by changes in the disc response to functional loading, may be identified in vivo from dynamic imaging collected during functional movements. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–7, 2019.