Takshan/R1 huggingface dataset:
Insights into the Conformational Ensemble of Human Islet Amyloid Polypeptide from Molecular Simulations.

BACKGROUND: The human islet amyloid polypeptide (hIAPP) can form insoluble fibrillar aggregates in the pancreas of patients with type 2 diabetes. However, increasing evidence suggests that, rather than the fibrils themselves, the hIAPP oligomers that appear on the fibrillation pathway are the toxic species for the pancreatic &#946; -cells. In the perspective of designing therapeutic inhibitors of hIAPP aggregation, it is thus crucial to better understand the mechanism of formation and to characterize the structures of these intermediate species. METHODS: However, it still remains a great challenge to experimentally study the hIAPP conformations, due to its intrinsically disordered characteristic and its fast aggregation propensity. Therefore, theoretical and computational approaches were used by many groups as complementary methods to investigate the hIAPP structural features involved in its oligomerization process. CONCLUSION: In this review, we examine the results provided by the hIAPP molecular simulations, in order to identify convergent insights into its conformational ensemble. Since hIAPP aggregation was shown to be modulated by the presence of lipid membranes, we survey molecular modeling studies of the peptide both in solution and membrane environment.
Endogenous factors and mechanisms of renoprotection and renal repair.

BACKGROUND: An imbalance between renal damaging molecules and nephroprotective factors contributes to the development and progression of kidney diseases. Molecules with renoprotective properties might serve as biomarkers, drug targets as well as therapeutic options themselves. MATERIALS AND METHODS: For this review, we generated a set of renoprotective factors based on GeneRIF (Gene Reference Into Function) information available at NCBI's PubMed. The final set of manually curated renoprotective factors was investigated with respect to tissue-specific expression, subcellular location distribution and involvement in biological processes using information from gene ontology as well as information from protein-protein interaction databases. We furthermore investigated the factors in the context of clinical trials of renal disease and diabetes. RESULTS: One hundred and ninety-three factors could be retrieved from the set of GeneRIFs on nephroprotection and renal repair. A large number of factors were either secretory molecules or plasma membrane receptors. Next to the elevated expression in renal tissue, also higher expression in connective tissue and pancreas was observed. The proteins could be assigned to the broad functional categories of cell proliferation and signalling, inflammatory response, apoptosis, blood pressure regulation as well as cellular response to different kinds of insults such as hypoxia, heat or mechanical stimulus. Eight factors are studied in clinical trials with additional ones being targeted by compounds. CONCLUSIONS: We have generated a set of renoprotective factors based on the literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials.
Prevalence and patterns of drug resistance among pulmonary tuberculosis patients in Hangzhou, China.

Background: To evaluate prevalence and patterns of drug resistance among pulmonary tuberculosis (TB) patients in Hangzhou City, China. Methods: Sputum samples of smear positive TB patients enrolled in 2011 and 2015 were collected and tested for drug susceptibility, and demographic and medical record data were extracted from the electronic database of China Information System for Disease Control and Prevention. Chi-square test was used to compare drug resistance prevalence between new and treated patients and between male and female patients, and Chi-square test for trend was used to compare the prevalence over calendar years 2011 and 2015. Results: Of 1326 patients enrolled in 2015, 22.3% had resistance to any first-line anti-TB drugs and 8.0% had multi-drug resistance (MDR); drug resistance rates among previously treated cases were significantly higher than among new cases. Significant declines of resistance to isoniazid, rifampin, ethambutol and streptomycin, and MDR from 2011 to 2015 were observed among previously treated patients, while a significant decline of resistance to rifampin was observed among new cases. Conclusions: While the prevalence of acquired drug resistance decreased due to due to implementation of DOTS-Plus program, the prevalence of primary drug resistance due to transmission remained high. Greater efforts should be made to screen drug resistance for case finding and to reduce transmission through improving the treatment and management of drug-resistant patients.
Complete genome sequence of Peptoclostridium difficile strain Z31.

BACKGROUND: Peptoclostridium (Clostridium) difficile is a spore-forming bacterium responsible for nosocomial infections in humans. It is recognized as an important agent of diarrhea and colitis in several animal species and a possible zoonotic agent. Despite the known importance of P. difficile infection in humans and animals, no vaccine or other effective measure to control the disease is commercially available. A possible alternative treatment for P. difficile infection is the use of a nontoxigenic strain of P. difficile as a competitive exclusion agent. However, a thorough knowledge of this strain is necessary for this purpose. We selected P. difficile Z31, a nontoxigenic strain (PCR ribotype 009), for investigation because it prevents P. difficile infection in a hamster model. RESULTS: The genome sequence of P. difficile Z31 is a circular chromosome of 4298,263 bp, with a 29.21 % GC content, encoding 4128 proteins, and containing 78 pseudogenes. This strain belongs to ST 3, clade 1, and has five phage regions in its genome. Genes responsible for resistance to tetracycline and erythromycin were detected and more importantly, Z31 also contains genes that promote spore production and stability, cell attachment, intestinal adherence, and biofilm formation. CONCLUSION: In this study, we present the first complete genome sequence of nontoxigenic P. difficile strain Z31. When the Z31 genome was compared with those of other isolates available in GenBank, including a draft genome of a nontoxigenic strain, several unique regions were evident. Z31 contains no toxin genes, but encodes several non-toxin virulence factors, which may favor host colonization.
Horizontal study of vaccinia virus infections in an endemic area: epidemiologic, phylogenetic and economic aspects.

Vaccinia virus (VACV), the etiological agent of bovine vaccinia (BV), is widespread in Brazil and present in most of the milk-producing regions. We conducted a horizontal study of BV in Bahia, a state of Brazil in which the production of milk is increasing. During 2011, human and bovine clinical samples were collected during outbreaks for BV diagnosis, virus isolation and molecular analysis. We collected data for epidemiological inferences. Vaccinia virus was detected in 87.7 % of the analyzed outbreaks, highlighting the effective circulation of VACV in Bahia. The molecular data showed the spreading of group 1 Brazilian VACV to Bahia. We observed a seasonal profile of BV, with its peak in the drier and cooler season. Manual milking was observed in 96 % of the visited properties, showing its importance to viral spread in herds. Under-notification of BV, ineffective animal trade surveillance, and bad milking practices have contributed to the spread of VACV in Brazil.
The associations between malaria, interventions, and the environment: a systematic review and meta-analysis.

BACKGROUND: Malaria transmission is driven by multiple factors, including complex and multifaceted connections between malaria transmission, socioeconomic conditions, climate and interventions. Forecasting models should account for all significant drivers of malaria incidence although it is first necessary to understand the relationship between malaria burden and the various determinants of risk to inform the development of forecasting models. In this study, the associations between malaria risk, environmental factors, and interventions were evaluated through a systematic review. METHODS: Five electronic databases (CAB Abstracts, EMBASE, Global Health, MEDLINE and ProQuest Dissertations & Theses) were searched for studies that included both the effects of the environment and interventions on malaria within the same statistical model. Studies were restricted to quantitative analyses and health outcomes of malaria mortality or morbidity, outbreaks, or transmission suitability. Meta-analyses were conducted on a subset of results using random-effects models. RESULTS: Eleven studies of 2248 potentially relevant articles that met inclusion criteria were identified for the systematic review and two meta-analyses based upon five results each were performed. Normalized Difference Vegetation Index was not found to be statistically significant associated with malaria with a pooled OR of 1.10 (95% CI 0.07, 1.71). Bed net ownership was statistically associated with decreasing risk of malaria, when controlling for the effects of environment with a pooled OR of 0.75 (95% CI 0.60, 0.95). In general, environmental effects on malaria, while controlling for the effect of interventions, were variable and showed no particular pattern. Bed nets ownership, use and distribution, have a significant protective effect while controlling for environmental variables. CONCLUSIONS: There are a limited number of studies which have simultaneously evaluated both environmental and interventional effects on malaria risk. Poor statistical reporting and a lack of common metrics were important challenges for this review, which must be addressed to ensure reproducibility and quality research. A comprehensive or inclusive approach to identifying malaria determinants using standardized indicators would allow for a better understanding of its epidemiology, which is crucial to improve future malaria risk estimations.
Assessment of Serum Vitamin B12 Levels and Other Metabolic Parameters in Subjects With Different Values of Bone Mineral Density.

Background: Controversial experimental and clinical evidences have raised questions regarding the role of B12 and insulin-like growth factor 1 (IGF-1) on osteoblast function and bone health. In this study, we aimed to determine if the serum levels of B12, IGF-1 and procollagen type 1 N-terminal propeptide (P1NP) are associated with different degrees of bone mineral density (BMD). Methods: A total of 287 subjects (190 women and 97 men; mean age 53 years) volunteered for evaluation of BMD and serum levels of B12, IGF-1 and P1NP; BMD at lumbar spine and proximal femur was evaluated by means of dual-energy X-ray absorption (DEXA) and expressed as T-score; serum concentrations of vitamin B12 and IGF1 were measured with a chemiluminescent immunoassay on Access II Beckman Coulter and DiaSorin Liaison XL analyzers, respectively; P1NP was assessed in 61 women and 35 men with reduced T-score on Roche Modular platform. Results: A total of 101 subjects (66 women and 35 men) had a reduced BMD (T-score < -1) or osteoporosis with a T-score < -2.5, while 186 (124 women and 62 men) had a normal BMD. No significant difference in the B12 levels was observed between the subjects with reduced BMD (mean 265.15 pg/mL, 95% CI: 236 - 294.25) and those with normal BMD (mean 243.91, 95% CI: 225.78 - 262.03) (P = 0.1990); lower levels of IGF-1 were observed in the group with reduced BMD (mean 138.7 pg/mL, 95% CI: 126.75 - 150.83) than in that with normal BMD (mean 167.34, 95% CI: 136.49 - 198.18) (P< 0.001); serum levels of P1NP were significantly lower in 22 subjects younger than 50 years (mean 44.8 ng/mL, 95% CI: 36.4 - 53.1) vs. 74 subjects > 50 years old (mean 53.3, 95% CI: 34.3 - 72.3) (P < 0.001), and in women (mean 45.3, 95% CI: 37.6 - 52.9) vs. men (mean 62, 95% CI: 23 - 101) (P < 0.001). Conclusion: We found no significant association between B12 levels and BMD, but significant associations of lower levels of IGF1 with reduced BMD and lower levels of P1NP with younger age and female sex were found; additional studies to further investigate the association of serum levels of B12, growth factors and biochemical turnover markers with human bone health are needed.
High positivity of mimivirus in inanimate surfaces of a hospital respiratory-isolation facility, Brazil.

BACKGROUND: Mimiviruses have been considered putative emerging pneumonia agents. Pneumonia is a leading cause of death related to infection throughout the world, with approximately 40% of cases presenting unknown etiology. Therefore, identifying new causative agents of community and nosocomial pneumonia is of major public health concern. OBJECTIVE: We evaluated the distribution of these viruses in samples collected from different environments of one of the largest hospitals in Brazilian Southeast. STUDY DESIGN: We analyzed, by molecular and virological approaches, the distribution of mimivirus in 242 samples collected from inanimate surfaces in different hospital facilities. RESULTS: A significant positivity of mimivirus in respiratory-isolation-facilities was observed (p<0.001). CONCLUSION: Although the role of mimivirus as etiological agents of pneumonia is still under investigation, our results demonstrates interesting correlations that strengthens the need for control over the occurrence of these viruses in hospital facilities.
Giving Voice to the Medically Under-Served: A Qualitative Co-Production Approach to Explore Patient Medicine Experiences and Improve Services to Marginalized Communities.

BACKGROUND: With an aging population, the appropriate, effective and safe use of medicines is a global health priority. However, "'medically under-served" patients continue to experience significant inequalities around access to healthcare services. AIM: This study forms part of a wider project to co-develop and evaluate a digital educational intervention for community pharmacy. The aim of this paper is to explore the medicine needs of patients from marginalized communities and suggest practical way on how services could be better tailored to their requirements. METHOD: Following ethical approval, qualitative data was gathered from: (1) workshops with patients and professionals (n = 57 attendees); and (2) qualitative semi-structured interviews (10 patients and 10 pharmacists). RESULTS: Our findings revealed that patients from marginalized communities reported poor management of their medical conditions and significant problems with adherence to prescribed medicines. Their experience of pharmacy services was found to be variable with many experiencing discrimination or disadvantage as a result of their status. DISCUSSION: This study highlights the plight of medically under-served communities and the need for policy makers to tailor services to an individual's needs and circumstances. Furthermore, patients and professionals can work in collaboration using a co-production approach to develop educational interventions for pharmacy service improvements.
A 3-biomarker-panel predicts renal outcome in patients with proteinuric renal diseases.

BACKGROUND: Clinical and histological parameters are valid prognostic markers in renal disease, although they may show considerable interindividual variability and sometimes limited prognostic value. Novel molecular markers and pathways have the potential to increase the predictive prognostic value of the so called "traditional markers". METHODS: Transcriptomics profiles from laser-capture microdissected proximal tubular epithelial cells from routine kidney biopsies were correlated with a chronic renal damage index score (CREDI), an inflammation score (INSCO), and clinical parameters. We used data from 20 renal biopsies with various proteinuric renal diseases with a median follow-up of 49 months (discovery cohort). For validation we performed microarrays from whole kidney biopsies from a second cohort consisting of 16 patients with a median follow-up time of 28 months (validation cohort). RESULTS: 562 genes correlated with the CREDI score and 285 genes correlated with the INSCO panel, respectively. 39 CREDI and 90 INSCO genes also correlated with serum creatinine at follow-up. After hierarchical clustering we identified 5 genes from the CREDI panel, and 10 genes from the INSCO panel, respectively, which showed kidney specific gene expression. After exclusion of genes, which correlated to each other by > 50% we identified VEGF-C from the CREDI panel and BMP7, THBS1, and TRIB1 from the INSCO panel. Traditional markers for chronic kidney disease progression and inflammation score predicted 44% of the serum creatinine variation at follow-up. VEGF-C did not further enhance the predictive value, but BMP7, THBS1 and TRIB1 together predicted 94% of the serum creatinine at follow up (p < 0.0001). The model was validated in a second cohort of patients yielding also a significant prediction of follow up creatinine (48%, p = 0.0115). CONCLUSION: We identified and validated a panel of three genes in kidney biopsies which predicted serum creatinine at follow-up and therefore might serve as biomarkers for kidney disease progression.
Design, innovation, and rural creative places: Are the arts the cherry on top, or the secret sauce?

OBJECTIVE: Creative class theory explains the positive relationship between the arts and commercial innovation as the mutual attraction of artists and other creative workers by an unobserved creative milieu. This study explores alternative theories for rural settings, by analyzing establishment-level survey data combined with data on the local arts scene. The study identifies the local contextual factors associated with a strong design orientation, and estimates the impact that a strong design orientation has on the local economy. METHOD: Data on innovation and design come from a nationally representative sample of establishments in tradable industries. Latent class analysis allows identifying unobserved subpopulations comprised of establishments with different design and innovation orientations. Logistic regression allows estimating the association between an establishment's design orientation and local contextual factors. A quantile instrumental variable regression allows assessing the robustness of the logistic regression results with respect to endogeneity. An estimate of design orientation at the local level derived from the survey is used to examine variation in economic performance during the period of recovery from the Great Recession (2010-2014). RESULTS: Three distinct innovation (substantive, nominal, and non-innovators) and design orientations (design-integrated, "design last finish," and no systematic approach to design) are identified. Innovation- and design-intensive establishments were identified in both rural and urban areas. Rural design-integrated establishments tended to locate in counties with more highly educated workforces and containing at least one performing arts organization. A quantile instrumental variable regression confirmed that the logistic regression result is robust to endogeneity concerns. Finally, rural areas characterized by design-integrated establishments experienced faster growth in wages relative to rural areas characterized by establishments using no systematic approach to design.
The survey of the patient received the epiduroscopic laser neural decompression.

BACKGROUND: Neuroplasty using a Racz catheter or epiduroscope and percutaneous endoscopic laser discectomy are performed as treatment for chronic refractory low back and/or lower extremity pain, but they are limited in that they cannot completely remove the causing pathology. Lately, epiduroscopic laser neural decompression (ELND) has been receiving attention as an alternative treatment, but there are insufficient reports of results. Hence we aimed to investigate and report the data in our hospital. METHODS: Seventy-seven patients were selected who had received ELND via the anterior and posterior epidural approach through the pain clinic in our hospital from March 2011 to July 2012. Their medical records including age, diagnosis, epiduroscopic findings and degree of symptom relief were investigated. The degree of symptom relief following the procedure was categorized into 5 stages of very good (5), good (4), no change (3), bad (2), and very bad (1) at 2 weeks and 1 month after the procedure. RESULTS: The subjects were 30 males and 47 females. Mean age was 54.6 for males and 59.6 for females, so the overall mean age was 58.1 years old, with the youngest being 23 and the oldest 88 years old. In epiduroscopic images of all patients, more than one situation of herniated disc, fibrous tissue and adhesion, or inflammation was observed. Sixty-seven patients (87.0%) showed symptom relief 2 weeks after the procedure and 63 patients (81.8%) showed relief after 1 month. CONCLUSIONS: ELND is considered to be an effective treatment alternative for chronic refractory low back and/or lower extremity pain, including lumbar disc herniation, lumbar spinal stenosis, and failed back surgery syndrome which cannot be alleviated with existing non-invasive conservative treatment.
Biological Control of Lettuce Drop and Host Plant Colonization by Rhizospheric and Endophytic Streptomycetes.

Lettuce drop, caused by the soil borne pathogen Sclerotinia sclerotiorum, is one of the most common and serious diseases of lettuce worldwide. Increased concerns about the side effects of chemical pesticides have resulted in greater interest in developing biocontrol strategies against S. sclerotiorum. However, relatively little is known about the mechanisms of Streptomyces spp. as biological control agents against S. sclerotiorum on lettuce. Two Streptomyces isolates, S. exfoliatus FT05W and S. cyaneus ZEA17I, inhibit mycelial growth of Sclerotinia sclerotiorum by more than 75% in vitro. We evaluated their biocontrol activity against S. sclerotiorum in vivo, and compared them to Streptomyces lydicus WYEC 108, isolated from Actinovate®. When Streptomyces spp. ( 10(6) CFU/mL) were applied to S. sclerotiorum inoculated substrate in a growth chamber 1 week prior lettuce sowing, they significantly reduced the risk of lettuce drop disease, compared to the inoculated control. Interestingly, under field conditions, S. exfoliatus FT05W and S. cyaneus ZEA17I protected lettuce from drop by 40 and 10% respectively, whereas S. lydicus WYEC 108 did not show any protection. We further labeled S. exfoliatus FT05W and S. cyaneus ZEA17I with the enhanced GFP (EGFP) marker to investigate their rhizosphere competence and ability to colonize lettuce roots using confocal laser scanning microscopy (CLSM). The abundant colonization of young lettuce seedlings by both strains demonstrated Streptomyces' capability to interact with the host from early stages of seed germination and root development. Moreover, the two strains were detected also on 2-week-old roots, indicating their potential of long-term interactions with lettuce. Additionally, scanning electron microscopy (SEM) observations showed EGFP-S. exfoliatus FT05W endophytic colonization of lettuce root cortex tissues. Finally, we determined its viability and persistence in the rhizosphere and endorhiza up to 3 weeks by quantifying its concentration in these compartments. Based on these results we conclude that S. exfoliatus FT05W has high potential to be exploited in agriculture for managing soil borne diseases barely controlled by available plant protection products.