Miracle-dz/UniFAR-FTUs huggingface dataset:
Cloning of Hexamethylene-bis-acetamide-inducible Transcript, HEXIM1, in Human Vascular Smooth Muscle Cells

The dedifferentiation and the abnormal growth of vascular smooth muscle cells (VSMC) is a major component of vascular diseases. Hexamethylene-bis-acetamide (I—lMBA) has recently been shown to modulate the differentiation and growth of VSMC in viz‘r0 and in viva. To determine the mechanism of this effect, we treated human coronary artery VSMC with HMBA and analyzed the effect of HMBA on gene expression by mRNA differential display. HMBA modulated the expression of a number of specific message fragments. By Marathon extension and cDNA screening, we isolated a novel gene, HEXIM1, that is up-regulated in HMBAstimulated VSMC. HEXIMI cDNA has a length of 3624 bp and encodes for a protein of 359 amino acids. Northern blot analysis demonstrated that the level of HEXIMI mRNA rapidly increased at 1 h after HMBA stimulation and was sustained for 48 h. These results suggest that l—lEXlM1 plays an important role in the regulation of the growth and differentiation of VSMC. Vascular smooth muscle cells (VSMC) are usually confined to the media of the vessel wall and maintain vascular tone by their contractile functions. However, abnormal proliferation of VSMC in the vessel intima is a major component of vascular diseases including atherosclerosis, vascular rejection, and restenosis following angioplasty (23, 26). It has been suggested that the contractile cells in the media are differentiated, whereas the proliferative cells in the intima become dedifferentiated (1, 2, 20). This proliferative phenotype of Correspondence to: Dr Masatoshi Kusuhara at the above address. Telephone: 81-45-753-2500 Fax: 81-45-753-2879 E-mail: mkusu@aurora.dti. ne.jp Sequence data from this article have been deposited with the DDBJ/EMBL/GenBank Data Libraries under Accession No. AB02ll79 VSMC is characterized by a reduction in the volume fraction of myofilaments, an increase in the proportion of synthetic organelles, the loss of contractile protein, and secretions of many proteins such as growth factors and extracellular matrix (17, 25). However, the precise molecular mechanisms underlying this process remain unclear. A differentiating agent, hexamethylene-bis acetamide (HMBA), has been shown to cause morphological and functional differentiation in several transformed cell lines and to inhibit cell proliferation in vz'z‘r0 and in vivo (22, 29). Recently, it was reported that HMBA inhibits the proliferation and induces the differentiation of VSMC in viz‘r0 (5, 8). Furthermore, we previously reported that HMBA prevented neointimal formation in a rat carotid balloon injury model (7). Evidence is accumulating that HMBA modulates the
Impedance cardiography for cuffless and non-invasive measurement of systolic blood pressure

In this study, we have used impedance cardiography to determine blood pressure (BP) cufflessly and non-invasively. We have devised a new parameter, QdZ [the duration measured from the foot of electrocardiogram (ECG) Q wave to the peak of impedance cardiogram (ICG)], for this purpose. Twenty-two subjects performed four minutes of treadmill exercise such that systolic BP (SBP) was increased significantly. We found that SBP was closely correlated with QdZ (R2=0.65) demonstrating the potential application of ICG to cuffless and non-invasive BP measurement.
Do Ethnic-Specific Long Term Care Facilities Improve Resident Quality of Life? Findings from the Japanese American Community

Abstract Research on resident/family perceptions of quality of life in residential care facilities for the elderly (RCFEs) has been sparse and has ignored ethnic-specific facilities. This qualitative inquiry compared interviews with Japanese American women in Japanese and non-Japanese RCFEs, family members, and administrators, to examine how ethnic features (e.g., Japanese language, food, staff) meet resident needs/preferences and their influence on the residents' quality of life. Residents and families differed in their preferences and perceptions of quality of life. Residents discussed invisible life process domains such as boredom, socialization, privacy, staff attentiveness/personal qualities, and autonomy. Family members emphasized structural aspects of the homes such as location, cleanliness, costs, home-like qualities, food, and Japanese care. While ethnic-specific institutions were unique in meeting certain needs (e.g., Japanese-speaking staff), culturally congruent characteristics alone did not provide a desired quality of life for residents, contrary to family perceptions. All institutions, including those with ethnic-specific services, need to integrate resident needs/wishes into their operations, adequate staffing, and meaningful activities to make life worth living.
Can we predict the outcome for people with patellofemoral pain? A systematic review on prognostic factors and treatment effect modifiers

Background Patellofemoral pain (PFP) is a multifactorial and often persistent knee condition. One strategy to enhance patient outcomes is using clinically assessable patient characteristics to predict the outcome and match a specific treatment to an individual. Aim A systematic review was conducted to determine which baseline patient characteristics were (1) associated with patient outcome (prognosis); or (2) modified patient outcome from a specific treatment (treatment effect modifiers). Methods 6 electronic databases were searched (July 2016) for studies evaluating the association between those with PFP, their characteristics and outcome. All studies were appraised using the Epidemiological Appraisal Instrument. Studies that aimed to identify treatment effect modifiers underwent a checklist for methodological quality. Results The 24 included studies evaluated 180 participant characteristics. 12 studies investigated prognosis, and 12 studies investigated potential treatment effect modifiers. Important methodological limitations were identified. Some prognostic studies used a retrospective design. Studies aiming to identify treatment effect modifiers often analysed too many variables for the limiting sample size and typically failed to use a control or comparator treatment group. 16 factors were reported to be associated with a poor outcome, with longer duration of symptoms the most reported (>4 months). Preliminary evidence suggests increased midfoot mobility may predict those who have a successful outcome to foot orthoses. Conclusions Current evidence can identify those with increased risk of a poor outcome, but methodological limitations make it difficult to predict the outcome after one specific treatment compared with another. Adequately designed randomised trials are needed to identify treatment effect modifiers.
Better way to determine the acute:chronic workload ratio?

We read with great interest the recent letter, “Time to bin the term ‘overuse’ injury: is ‘training load error’ a more accurate term? ”1 and in particular its associated PostScript correspondence, “Are rolling averages a good way to assess training load for injury prevention? ”2 We are currently investigating the association between training loads and injury risk,3 and so we have also been considering the best way to model this relationship. We share Dr Menaspa's concerns regarding the use of rolling averages for the calculation of ‘acute’ and ‘chronic’ loads. Namely, that they fail to account for the decaying nature of fitness and …
Causes of vertical transmission of hepatitis B virus under the at‐risk prevention strategy in Japan

The number of hepatitis B virus (HBV) carrier babies has decreased markedly since the introduction in Japan of an “at‐risk” strategy for preventing HBV infection. However, elimination of HBV infection from our country appears difficult. To clarify the limitations of the at‐risk strategy for preventing vertical transmission of HBV, causes of vertical transmission in a single hospital were retrospectively analyzed. The following causes were presumed in 17 carrier pediatric cases: five patients had prenatal HBV infection, HBV infection during/after the immunization program was confirmed in five cases, two patients had prenatal infection or infection during the immunization program and three cases were caused by human error (by the patients' guardians). Because their mothers were HBV‐negative at screening and only developed acute hepatitis B in the perinatal period, another two cases (Cases 3 and 10) did not undergo immunization because they were not subjects of the at‐risk strategy. Sequence analyses in ten patients revealed genotype C (subgenotype, C2/Ce) in nine cases and genotype A (subgenotype, A2/Ae) in one case (Case 3). In Japan, HBV subgenotype Ae has recently been found more frequently among sexually active men with acute hepatitis. There are concerns that horizontal transmission of HBV from these men to their pregnant partners could increase. These data suggest clear limitations to the at‐risk strategy in Japan and the possibility that the increase in genotype A may influence vertical transmission of HBV.
Arginine methylation regulates antibody responses through modulating cell division and isotype switching in B cells

Protein arginine methylation plays crucial roles, including signal transduction, transcriptional control, cell proliferation and/or differentiation. B cells undergo clonal division, isotype switching and differentiate into antibody forming cells following stimulation with Toll‐like receptor‐ligand, lipopolysaccharide (LPS) and T cell‐derived signals, including CD40‐ligand (CD40‐L) and interleukin 4 (IL‐4). Whether protein arginine methylation affects B cell division and/or isotype switching to IgG1 in response to LPS, IL‐4, and CD40‐L was examined using the arginine methyl transferase inhibitor adenosine‐2′,3′‐dialdehyde (AdOx). Addition of AdOx substantially reduced the number of division cycles of stimulated B cells, whereas cell viability remained intact. Upon stimulation with LPS/IL‐4/CD40‐L, the proportion of surface IgG1 positive cells in each division cycle was slightly diminished by AdOx. However, the degree of expression of γ1 germ line transcript and activation‐induced cytidine deaminase (AID) in response to LPS/IL‐4/CD40‐L were unaffected by addition of AdOx, suggesting that AdOx influences class switch recombination independent of AID expression through transcriptional control. Taken together, arginine methylation appears to be involved in B cell isotype switching, as well as in clonal expansion of B cells in response to LPS/IL‐4/CD40‐L.
Evaluation and Optimization of Virtual Screening Workflows with DEKOIS 2.0 - A Public Library of Challenging Docking Benchmark Sets

The application of molecular benchmarking sets helps to assess the actual performance of virtual screening (VS) workflows. To improve the efficiency of structure-based VS approaches, the selection and optimization of various parameters can be guided by benchmarking. With the DEKOIS 2.0 library, we aim to further extend and complement the collection of publicly available decoy sets. Based on BindingDB bioactivity data, we provide 81 new and structurally diverse benchmark sets for a wide variety of different target classes. To ensure a meaningful selection of ligands, we address several issues that can be found in bioactivity data. We have improved our previously introduced DEKOIS methodology with enhanced physicochemical matching, now including the consideration of molecular charges, as well as a more sophisticated elimination of latent actives in the decoy set (LADS). We evaluate the docking performance of Glide, GOLD, and AutoDock Vina with our data sets and highlight existing challenges for VS tools. All DEKOIS 2.0 benchmark sets will be made accessible at http://www.dekois. com.
Periconceptional Care: An Experiment in Community Genetics

Periconceptional care was established in 1984 in Hungary and was expanded to a national network in 1989. Periconceptional care consisting of counseling, examinations and medical interventions for voluntary and eligible couples based on three steps: check-up of reproductive health (i.e. preconceptional screening), a 3-month preparation for conception, and best possible protection in early pregnancy for the most sensitive early development of the embryo. Periconceptional care is provided and/or supervised by qualified nurses. This care helps participants with a positive family history, case history, a genitourinary infection or infertility to have a more effective access to secondary care. Periconceptional care is optimal for introducing periconceptional folic acid/multivitamin supplementation and for reducing smoking and alcohol consumption in females prior to conception. The rate of major congenital abnormalities in the children of couples attending for periconceptional care (20.6/1,000) was significantly lower than expected (about 40/1,000) during the study period. Periconceptional care also provides an opportunity for the primary prevention of common complex diseases, e.g. coronary artery disorders; it may be called a ‘euphenic’ model. In conclusion, periconceptional care is feasible and has many benefits, because proper preparation for conception is the earliest and probably the most important approach for health promotion and for the prevention of congenital abnormalities.
Elaborate Ligand-Based Modeling Coupled with Multiple Linear Regression and k Nearest Neighbor QSAR Analyses Unveiled New Nanomolar mTOR Inhibitors

The mammalian target of rapamycin (mTOR) has an important role in cell growth, proliferation, and survival. mTOR is frequently hyperactivated in cancer, and therefore, it is a clinically validated target for cancer therapy. In this study, we combined exhaustive pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent mTOR inhibitors employing 210 known mTOR ligands. Genetic function algorithm (GFA) coupled with k nearest neighbor (kNN) and multiple linear regression (MLR) analyses were employed to build self-consistent and predictive QSAR models based on optimal combinations of pharmacophores and physicochemical descriptors. Successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve (ROC) profiles. Optimal QSAR models and their associated pharmacophore hypotheses were validated by identification and experimental evaluation of several new promising mTOR inhibitory leads retrieved from the National Cancer Institute (NCI) structural database. The most potent hit illustrated an IC50 value of 48 nM.
Ultrasound elastography to determine the layered mechanical properties of articular cartilage and the importance of such structural characteristics under load

Articular cartilage is an important load bearing surface in joints. Prone to damage and with limited self-repair ability, it is of interest to tissue engineers. Tissue implant design requires full mechanical characterisation of healthy native tissue. A layered organisation of reinforcing collagen fibrils exists in healthy articular cartilage and is believed to be important for correct tissue function. However, the effect of this on the local depth-dependent elasticity is poorly characterised. In this study, quasi-static ultrasound elastography is used both to compare the depth-dependent elastic properties of cartilage structures with two different fibril arrangements and to monitor changes in the elastic properties of engineered samples during development. Results show global and local elastic properties of the native tissues and highlight the differences caused by fibril architecture. At increasing culture periods, results from the engineered tissue demonstrate an increase in elastic stiffness and the time taken to reach equilibrium under a quasi-static displacement. The study suggests suitability of ultrasound elastography for design and monitoring engineered articular cartilage.
Medial tibial stress syndrome can be diagnosed reliably using history and physical examination

Background The majority of sporting injuries are clinically diagnosed using history and physical examination as the cornerstone. There are no studies supporting the reliability of making a clinical diagnosis of medial tibial stress syndrome (MTSS). Aim Our aim was to assess if MTSS can be diagnosed reliably, using history and physical examination. We also investigated if clinicians were able to reliably identify concurrent lower leg injuries. Methods A clinical reliability study was performed at multiple sports medicine sites in The Netherlands. Athletes with non-traumatic lower leg pain were assessed for having MTSS by two clinicians, who were blinded to each others’ diagnoses. We calculated the prevalence, percentage of agreement, observed percentage of positive agreement (Ppos), observed percentage of negative agreement (Pneg) and Kappa-statistic with 95%CI. Results Forty-nine athletes participated in this study, of whom 46 completed both assessments. The prevalence of MTSS was 74%. The percentage of agreement was 96%, with Ppos and Pneg of 97% and 92%, respectively. The inter-rater reliability was almost perfect; k=0.89 (95% CI 0.74 to 1.00), p<0.000001. Of the 34 athletes with MTSS, 11 (32%) had a concurrent lower leg injury, which was reliably noted by our clinicians, k=0.73, 95% CI 0.48 to 0.98, p<0.0001. Conclusion Our findings show that MTSS can be reliably diagnosed clinically using history and physical examination, in clinical practice and research settings. We also found that concurrent lower leg injuries are common in athletes with MTSS.
Toward Fully Automated High Performance Computing Drug Discovery: A Massively Parallel Virtual Screening Pipeline for Docking and Molecular Mechanics/Generalized Born Surface Area Rescoring to Improve Enrichment

In this work we announce and evaluate a high throughput virtual screening pipeline for in-silico screening of virtual compound databases using high performance computing (HPC). Notable features of this pipeline are an automated receptor preparation scheme with unsupervised binding site identification. The pipeline includes receptor/target preparation, ligand preparation, VinaLC docking calculation, and molecular mechanics/generalized Born surface area (MM/GBSA) rescoring using the GB model by Onufriev and co-workers [J. Chem. Theory Comput. 2007, 3, 156-169]. Furthermore, we leverage HPC resources to perform an unprecedented, comprehensive evaluation of MM/GBSA rescoring when applied to the DUD-E data set (Directory of Useful Decoys: Enhanced), in which we selected 38 protein targets and a total of ∼0.7 million actives and decoys. The computer wall time for virtual screening has been reduced drastically on HPC machines, which increases the feasibility of extremely large ligand database screening with more accurate methods. HPC resources allowed us to rescore 20 poses per compound and evaluate the optimal number of poses to rescore. We find that keeping 5-10 poses is a good compromise between accuracy and computational expense. Overall the results demonstrate that MM/GBSA rescoring has higher average receiver operating characteristic (ROC) area under curve (AUC) values and consistently better early recovery of actives than Vina docking alone. Specifically, the enrichment performance is target-dependent. MM/GBSA rescoring significantly out performs Vina docking for the folate enzymes, kinases, and several other enzymes. The more accurate energy function and solvation terms of the MM/GBSA method allow MM/GBSA to achieve better enrichment, but the rescoring is still limited by the docking method to generate the poses with the correct binding modes.
Caring for persons with Parkinson’s disease in care homes: Perceptions of residents and their close relatives, and an associated review of residents’ care plans

Abstract Through qualitative in-depth interviews, we collected the views of persons with Parkinson’s disease (pwPD) and their close relatives in care homes to establish their collective views of the effectiveness of care. We also reviewed the corresponding care plans. Drawing on these two forms of data collection, we compared similarities and differences between the qualitative interview data and the care plan analysis to elaborate on the experience of residential care for pwPD. Close relatives of care home residents can be a fruitful source of information for care home staff, throughout the care planning process, especially in relation to the specific needs of a pwPD. Although health and social policy advocate active collaboration between people with long-term conditions, their families, and their formal carers, there is limited evidence of such collaboration in the data examined here. There is an apparent shortfall in the knowledge and understanding of PD among care home staff. There are important pragmatic (e.g. drug administration) as well as psycho-social reasons for flexibility in routine care provision to meet the dynamic needs of pwPD. The findings here support the need for further, larger scale research into the quality of care for pwPD who are care home residents.
The usefulness of semi‐solid medium in the isolation of highly virulent Leptospira strains from wild rats in an urban area of Fukuoka, Japan

Leptospirosis is a worldwide zoonosis. The importance of urban leptospirosis is recognized in Japan: urban rats carry pathogenic leptospires and people acquire these pathogens through contact with surface water or soil contaminated by the urine of the infected animals. To determine the current Leptospira carriage rate in urban rats, 29 wild rats were trapped in the central area of Fukuoka and strains isolated from their kidneys and urine analyzed. When semi‐solid Korthof's medium containing 0.1% agar was used for isolation, 72.2% and 30.8% of the kidney and urine cultures, respectively, were found to be Leptospira‐positive. The isolates belonged to Leptospira interrogans, and were classified into two groups (serogroups Pomona and Icterohaemorrhagiae) based on the results of gyrB sequence analysis and microscopic agglutination testing (MAT). Strains belonging to serogroup Icterohemorrhagiae grew well in liquid medium. On the other hand, serogroup Pomona isolates multiplied very little in liquid medium, but did grow in a semi‐solid medium. Although strains belonging to serogroup Pomona have not been recognized as native to Japan, this strain may be widely distributed in urban rats. Representative strains from each group were found to be highly pathogenic to hamsters. Our findings should serve as a warning that it is still possible to become infected with leptospires from wild rats living in inner cities of Japan. Furthermore, the use of semi‐solid medium for culture will improve the isolation rate of leptospires from the kidneys of wild rats.