Takshan/R1 huggingface dataset:
Willingness to participate in weight-related research as reported by patients in PCORnet clinical data research networks.

Background: Since 2014 the Patient Centered Outcomes Research Institute (PCORI) has funded 13 Clinical Data Research Networks (CDRNs) around the country to support large-scale comparative effectiveness research and pragmatic clinical trials. To provide guidance for future recruitment efforts among CDRNs this study described differential willingness to participate in weight-related research by body mass index (BMI) and sociodemographic characteristics. Methods: During 2014-2016 we surveyed participants from three CDRNs including the Mid-South CDRN, REACHnet, and the PaTH Network, representing 14 medical centers. Participants were eligible if they were ≥18 years, had ≥2 weights and ≥1 height in the electronic health record. Respondents were recruited face-to-face in primary care and specialty clinics, and via email from doctors' offices, patient registries and health systems' patient portals. Data was collected on willingness to participate in weight-related research (four items combined into a single scale; range 4-12), BMI, and sociodemographics (age, sex, number of people in household, marital status, education level, race, and ethnicity). Adjusted ordinal regression models tested associations between participant characteristics and willingness to participate in weight-related research. Results: Among 11,624 respondents, mean BMI was 29.6 (SD 7.6) kg/m2. Mean willingness to participate in weight-related research was 7.1 (SD 2.5). More respondents were willing to participate in studies with lower burden: healthy lifestyles (82.2%), genetics (71.3%), medication (52.2%), and surgery (22.6%). In adjusted models, higher BMI was associated with greater willingness to participate in weight-related research (OR = 1.13) as were younger age (OR = 0.98), being a woman (OR 1.59), and college education (OR = 1.72) (all p < 0.001). Conclusions: Associations among BMI, age, sex, and education level with willingness to participate in weight-related research highlight the need for future research to reduce barriers for populations less willing to engage in weight-related research.
A standardized approach to treat complex aortic valve endocarditis: a case series.

BACKGROUND: Surgical treatment of complicated aortic valve endocarditis often is challenging, even for experienced surgeons. We aim at demonstrating a standardized surgical approach by stentless bioprostheses for the treatment of aortic valve endocarditis complicated by paravalvular abscess formation. METHODS: Sixteen patients presenting with aortic valve endocarditis (4 native and 12 prosthetic valves) and paravalvular abscess formation at various localizations and to different extents were treated by a standardized approach using stentless bioprostheses. The procedure consisted of thorough debridement, root replacement with reimplantation of the coronary arteries and correction of accompanying pathologies (aortoventricular and aortomitral dehiscence, septum derangements, Gerbode defect, total atrioventricular conduction block, mitral and tricuspid valve involvement). RESULTS: All highly complex patients included (14 males and 2 females; median age 63 years [range 31-77]) could be successfully treated with stentless bioprostheses as aortic root replacement. Radical surgical debridement of infected tissue with anatomical recontruction was feasible. Although predicted operative mortality was high (median logarithmic EuroSCORE I of 40.7 [range 12.8-68.3]), in-hospital and 30-day mortality rates were favorable (18.8 and 12.5% respectively). CONCLUSIONS: Repair of active aortic valve endocarditis complicated by paravalvular abscess formation and destruction of the left ventricular outflow tract with stentless bioprosthesis is a valuable option for both native and prosthetic valves. It presents a standardized approach with a high success rate for complete debridement, is readily available, and yields comparable clinical outcomes to the historical gold standard, repair by homografts. Additionally, use of one type of prosthesis reduces logistical issues and purchasing costs.
Diverse expression of TNF-α and CCL27 in serum and blister of Stevens-Johnson syndrome/toxic epidermal necrolysis.

Background: The pathogenesis of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is not fully understood. Our previous study reported that chemokine CCL27 was overexpressed in serum of SJS/TEN patients. The objective of this study was to investigate the levels of CCL27 and TNF-α in serum and blister fluid from patients with SJS/TEN during the acute stage or resolution phase. Methods: A total of 27 patients with SJS/TEN and 39 healthy donors were recruited to the study. Serum and vesicular levels of CCL27 and TNF-α were determined by enzyme-linked immunosorbent assays. Results: Serum levels of CCL27 and TNF-α were significantly elevated in patients with SJS/TEN during the acute stage as compared to the resolution phase and also compared with levels observed in normal controls (P = 0.001/< 0.001; P = 0.012/< 0.001). Serum TNF-α levels were significantly higher in patients with SJS/TEN during the resolution phase compared with normal controls (P < 0.001). Serum CCL27 levels were positively correlated with TNF-α levels during the acute stage (r s = 0.660; P < 0.001). Blister fluid exhibited much lower CCL27 levels than serum did during the acute stage (P = 0.008). TNF-α levels were much higher in vesicles in contrast to serum from acute stage (P = 0.040) as well as serum from resolution phase (P = 0.029). Conclusions: Our study demonstrated roles of CCL27 and TNF-α in promoting the course of SJS/TEN. CCL27 may act early in the course of disease, via the circulation, whereas TNF-α acts throughout the course of disease, in skin lesions.
Culturally Competent Care for Sexual and Gender Minority Patients at National Cancer Institute-Designated Comprehensive Cancer Centers.

PURPOSE: This study sought to identify the policies and guidelines regarding culturally competent care of sexual and gender minority (SGM) cancer patients and survivors at National Cancer Institute (NCI)-Designated Comprehensive Cancer Centers. METHODS: This study used an in-depth interview qualitative approach. Semistructured interviews were conducted via telephone with representatives from 21 of the 45 NCI-Designated Comprehensive Cancer Centers in 2015. Verbatim transcripts were created from the audiotapes for content analysis. RESULTS: Two main themes were identified as follows: (1) patient-focused experiences and support and (2) organization-focused development activities. Most of the cancer centers in this study had an advisory committee to assist with SGM policies and guidelines. Despite the existence of these committees, the majority of centers did not have explicit policies, guidelines, or routine practices addressing the following issues: the collection and integration of sexual orientation and gender identity information in the medical record, gender-neutral language on patient forms, patient educational materials with SGM-specific health concerns, SGM-specific support for cancer survivors, or required SGM-specific cultural competency trainings for medical and nonmedical staff. CONCLUSION: In general, the cancer centers in this study lacked institutional policies, guidelines, and practices focused on patient-centered cancer care for SGM populations. Coordinated efforts are needed to systemically improve patient-centered cancer care for these populations.
Prognostic Relevance of Mucinous Subtype in a Population-based Propensity Score Analysis of 40,083 Rectal Cancer Patients.

BACKGROUND: The prognostic relevance of mucinous histology in colorectal cancer remains unclear, especially for rectal neoplasms. The objective of this study was to evaluate if mucinous subtype has a relevant impact on overall survival (OS) and cancer-specific survival (CSS) of patients with adenocarcinomas of the rectum. METHODS: On the basis of the data set of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute of the United States, patients with rectal cancer between 2004 and 2011 were identified. Risk-adjusted Cox regression analysis and propensity score methods were used to assess OS and CSS. RESULTS: In total, 40,083 patients with stage I-IV rectal cancer, of whom 2483 (6.2 %) had mucinous histology, were included in this study. In unadjusted analysis, the 5-year OS and CSS for patients with a mucinous adenocarcinoma was 54.3 % [95 % confidence interval (CI) 52.0-56.7] and 61.4 % (95 % CI 59.1-63.9) compared to 66.4 % (95 % CI 65.8-67.0) and 74.5 % (95 % CI 73.9-75.1) for patients with nonmucinous adenocarcinoma (P < 0.001). The survival disadvantage persisting in risk-adjusted Cox proportional hazard regression analysis [hazard ratio (HR) 1.23, 95 % CI 1.15-1.31, P < 0.001 and 1.25, 95 % CI 1.16-1.35, P < 0.001) disappeared after propensity score matching (OS: HR = 0.96, 95 % CI 0.76-1.21, P = 0.722; CSS: HR 1.06, 95 % CI 0.80-1.40, P = 0.693). CONCLUSIONS: This population-based, propensity score matched analysis shows that mucinous histology itself does not constrain survival in rectal cancer patients. Therefore, treatment decisions should not be different according to mucinous histology.
Metabolic Syndrome and Chronic Renal Disease.

Background: The influence of metabolic syndrome (MetS) on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR) and/or the presence of microalbuminuria/macroalbuminuria. METHODS: 149 patients (77 males/72 females) were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components) including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x² = 50.3, p = 0.001 and x² = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence showed an odds 5.3-fold (1.6-17.8) higher for low eGFR and 3.2-fold (1.2-8.8) higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1-11.3). Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x² = 11.8, p = 0.003, x² = 11.4, p = 0.003 and x² = 9.1, p = 0.01 respectively), and it was mildly associated with a low HDL-C (x² = 5.7, p = 0.06). A significant association between classified eGFR and both high triglycerides and hypertension (x² = 9.7, p = 0.04 and x² = 16.1, p = 0.003 respectively) was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.
Comparing private and public transport access to diabetic health services across inner, middle, and outer suburbs of Melbourne, Australia.

BACKGROUND: Melbourne, Australia is experiencing rapid population growth, with much of this occurring in metropolitan outer suburban areas, also known as urban growth areas. Currently little is known about differences in travel times when using private and public transport to access primary and secondary services across Melbourne's urban growth areas. Plan Melbourne Refresh, a recent strategic land use document has called for a 20 min city, which is where essential services including primary health care, can be accessed within a 20 min journey. Type 2 diabetes mellitus (T2DM) is a major chronic condition in Australia, with some of Melbourne's growth areas having some of the highest prevalence across Australia. This study explores travel times to diabetic health care services for populations residing in inner, middle and outer suburbs of metropolitan Melbourne. METHOD: Geographic information systems (GIS) software were used to map the location of selected diabetic primary and secondary health care service providers across metropolitan inner, middle, outer established, outer urban growth and outer fringe areas of Melbourne. An origin-destination matrix was used to estimate travel distances from point of origin (using a total of approximately 50,000 synthetic residential addresses) to the closest type of each diabetic health care service provider (destinations) across Melbourne. ArcGIS was used to estimate travel times for private transport and public transport; comparisons were made by area. RESULTS: Our study indicated increased travel times to diabetic health services for people living in Melbourne's outer growth and outer fringe areas compared with the rest of Melbourne (inner, middle and outer established). Compared with those living in inner city areas, the median time spent travelling to diabetic services was between 2.46 and 23.24 min (private motor vehicle) and 12.01 and 43.15 min (public transport) longer for those living in outer suburban areas. Irrespective of travel mode used, results indicate that those living in inner and middle suburbs of Melbourne have shorter travel times to access diabetic health services, compared with those living in outer areas of Melbourne. Private motor vehicle travel times were approximately 4 to 5 times faster than public transport modes to access diabetic health services in all areas. CONCLUSION: Those living in new urban growth communities spend considerably more time travelling to access diabetic health services - particularly specialists - than those living in established areas across Melbourne.
Resounding failure to replicate links between developmental language disorder and cerebral lateralisation.

Background: It has been suggested that failure to establish cerebral lateralisation may be related to developmental language disorder (DLD). There has been weak support for any link with handedness, but more consistent reports of associations with functional brain lateralisation for language. The consistency of lateralisation across different functions may also be important. We aimed to replicate previous findings of an association between DLD and reduced laterality on a quantitative measure of hand preference (reaching across the midline) and on language laterality assessed using functional transcranial Doppler ultrasound (fTCD). Methods: From a sample of twin children aged from 6;0 to 11;11 years, we identified 107 cases of DLD and 156 typically-developing comparison cases for whom we had useable data from fTCD yielding a laterality index (LI) for language function during an animation description task. Handedness data were also available for these children. Results: Indices of handedness and language laterality for this twin sample were similar to those previously reported for single-born children. There were no differences between the DLD and TD groups on measures of handedness or language lateralisation, or on a categorical measure of consistency of left hemisphere dominance. Contrary to prediction, there was a greater incidence of right lateralisation for language in the TD group (19.90%) than the DLD group (9.30%), confirming that atypical laterality is not inconsistent with typical language development. We also failed to replicate associations between language laterality and language test scores. Discussion and Conclusions: Given the large sample studied here and the range of measures, we suggest that previous reports of atypical manual or language lateralisation in DLD may have been false positives.
Analysis of MAPK and MAPKK gene families in wheat and related Triticeae species.

BACKGROUND: The mitogen-activated protein kinase (MAPK) family is involved in signal transduction networks that underpin many different biological processes in plants, ranging from development to biotic and abiotic stress responses. To date this class of enzymes has received little attention in Triticeae species, which include important cereal crops (wheat, barley, rye and triticale) that represent over 20% of the total protein food-source worldwide. RESULTS: The work presented here focuses on two subfamilies of Triticeae MAPKs, the MAP kinases (MPKs), and the MAPK kinases (MKKs) whose members phosphorylate the MPKs. In silico analysis of multiple Triticeae sequence databases led to the identification of 152 MAPKs belonging to these two sub-families. Some previously identified MAPKs were renamed to reflect the literature consensus on MAPK nomenclature. Two novel MPKs, MPK24 and MPK25, have been identified, including the first example of a plant MPK carrying the TGY activation loop sequence common to mammalian p38 MPKs. An EF-hand calcium-binding domain was found in members of the Triticeae MPK17 clade, a feature that appears to be specific to Triticeae species. New insights into the novel MEY activation loop identified in MPK11s are offered. When the exon-intron patterns for some MPKs and MKKs of wheat, barley and ancestors of wheat were assembled based on transcript data in GenBank, they showed deviations from the same sequence predicted in Ensembl. The functional relevance of MAPKs as derived from patterns of gene expression, MPK activation and MKK-MPK interaction is discussed. CONCLUSIONS: A comprehensive resource of accurately annotated and curated Triticeae MPK and MKK sequences has been created for wheat, barley, rye, triticale, and two ancestral wheat species, goat grass and red wild einkorn. The work we present here offers a central information resource that will resolve existing confusion in the literature and sustain expansion of MAPK research in the crucial Triticeae grains.
Genome assembly of the Pink Ipê (Handroanthus impetiginosus, Bignoniaceae), a highly valued, ecologically keystone Neotropical timber forest tree.

Background: Handroanthus impetiginosus (Mart. ex DC.) Mattos is a keystone Neotropical hardwood tree widely distributed in seasonally dry tropical forests of South and Mesoamerica. Regarded as the "new mahogany," it is the second most expensive timber, the most logged species in Brazil, and currently under significant illegal trading pressure. The plant produces large amounts of quinoids, specialized metabolites with documented antitumorous and antibiotic effects. The development of genomic resources is needed to better understand and conserve the diversity of the species, to empower forensic identification of the origin of timber, and to identify genes for important metabolic compounds. Findings: The genome assembly covers 503.7 Mb (N50 = 81 316 bp), 90.4% of the 557-Mbp genome, with 13 206 scaffolds. A repeat database with 1508 sequences was developed, allowing masking of ∼31% of the assembly. Depth of coverage indicated that consensus determination adequately removed haplotypes assembled separately due to the extensive heterozygosity of the species. Automatic gene prediction provided 31 688 structures and 35 479 messenger RNA transcripts, while external evidence supported a well-curated set of 28 603 high-confidence models (90% of total). Finally, we used the genomic sequence and the comprehensive gene content annotation to identify genes related to the production of specialized metabolites. Conclusions: This genome assembly is the first well-curated resource for a Neotropical forest tree and the first one for a member of the Bignoniaceae family, opening exceptional opportunities to empower molecular, phytochemical, and breeding studies. This work should inspire the development of similar genomic resources for the largely neglected forest trees of the mega-diverse tropical biomes.
LRRK2 p.Ile1371Val Mutation in a Case with Neuropathologically Confirmed Multi-System Atrophy.

BACKGROUND: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. OBJECTIVE: To genetically and pathologically characterize a case with a LRRK2, p.Ile1371Val rare variant and pathologically proven MSA. METHODS: From the brain donation program at the Parkinson's Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD (n = 20), MSA (n = 4), or PSP (n = 2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases. RESULTS: We identified a known LRRK2, p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was more affected than the striatonigral system. CONCLUSIONS: Our data suggest that genetic variants in the LRRK2 gene can present clinically and neuropathologically as MSA. One other LRRK2 genetic variant (LRRK2, p.Ile2020Thr) has been reported with a neuropathological diagnosis of MSA. Interestingly, the LRRK2 variant (LRRK2, p.Ile1371Val) identified here has been reported previously in a postmortem case with Lewy body PD.Future studies are critical to discover the mechanisms leading to different neurodegenerative trajectories both in neuronal and glial cell populations.
Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is clinically defined and characterised by persistent disabling tiredness and exertional malaise, leading to functional impairment. METHODS: This study introduces the weighted standing time (WST) as a proxy for ME/CFS severity, and investigates its behaviour in an Australian cohort. WST was calculated from standing time and subjective standing difficulty data, collected via orthostatic intolerance assessments. The distribution of WST for healthy controls and ME/CFS patients was correlated with the clinical criteria, as well as pathology and cytokine markers. Included in the WST cytokine analyses were activins A and B, cytokines causally linked to inflammation, and previously demonstrated to separate ME/CFS from healthy controls. Forty-five ME/CFS patients were recruited from the CFS Discovery Clinic (Victoria) between 2011 and 2013. Seventeen healthy controls were recruited concurrently and identically assessed. RESULTS: WST distribution was significantly different between ME/CFS participants and controls, with six diagnostic criteria, five analytes and one cytokine also significantly different when comparing severity via WST. On direct comparison of ME/CFS to study controls, only serum activin B was significantly elevated, with no significant variation observed for a broad range of serum and urine markers, or other serum cytokines. CONCLUSIONS: The enhanced understanding of standing test behaviour to reflect orthostatic intolerance as a ME/CFS symptom, and the subsequent calculation of WST, will encourage the greater implementation of this simple test as a measure of ME/CFS diagnosis, and symptom severity, to the benefit of improved diagnosis and guidance for potential treatments.