Takshan/R1 huggingface dataset:
Association of dietary patterns and hyperuricemia: a cross-sectional study of the Yi ethnic group in China.

Background: Diet plays an important role in the development of hyperuricemia (HUA), but evidence for association between overall dietary patterns and HUA is scarce and inconsistent. The present study aims to explore association of dietary patterns and HUA among the Yi ethnic group of China. Methods: This is a cross-sectional study involving people aged more than 18 years. Principal component factor analysis (PCFA) on food groups from a semi-quantitative 52-item food frequency questionnaire was applied to identify dietary patterns. HUA status was regressed on tertiles of factor scores to estimate prevalence ratio (PR) by using log-binomial model. Results: Of the 1,893 participants (18-96 years), 398 (21.0%) were diagnosed with HUA. Three dietary patterns were identified: 'plant-based', 'animal products', and 'mixed food'. The 'animal products' was characterized by high intake of fish, animal giblets, fresh meat, and wheat products. After adjustment for potential confounders, the highest tertile of 'animal products' pattern score was associated with higher prevalence of HUA when compared with the lowest tertile (PR: 1.34, 95% CI: 1.06-1.70). The other two patterns were not related to HUA. Conclusions: 'Animal products' dietary pattern was correlated with HUA among the Yi ethnic group of China.
Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data.

BACKGROUND: Whole-genome bisulfite sequencing (WGBS) is becoming an increasingly accessible technique, used widely for both fundamental and disease-oriented research. Library preparation methods benefit from a variety of available kits, polymerases and bisulfite conversion protocols. Although some steps in the procedure, such as PCR amplification, are known to introduce biases, a systematic evaluation of biases in WGBS strategies is missing. RESULTS: We perform a comparative analysis of several commonly used pre- and post-bisulfite WGBS library preparation protocols for their performance and quality of sequencing outputs. Our results show that bisulfite conversion per se is the main trigger of pronounced sequencing biases, and PCR amplification builds on these underlying artefacts. The majority of standard library preparation methods yield a significantly biased sequence output and overestimate global methylation. Importantly, both absolute and relative methylation levels at specific genomic regions vary substantially between methods, with clear implications for DNA methylation studies. CONCLUSIONS: We show that amplification-free library preparation is the least biased approach for WGBS. In protocols with amplification, the choice of bisulfite conversion protocol or polymerase can significantly minimize artefacts. To aid with the quality assessment of existing WGBS datasets, we have integrated a bias diagnostic tool in the Bismark package and offer several approaches for consideration during the preparation and analysis of WGBS datasets.
Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia.

Genetic etiology of psychopathology symptoms and cognitive performance in schizophrenia is supported by candidate gene and polygenic risk score (PRS) association studies. Such associations are reported to be dependent on several factors - sample characteristics, illness phase, illness severity etc. We aimed to examine if schizophrenia PRS predicted psychopathology symptoms and cognitive performance in patients with chronic schizophrenia. We also examined if schizophrenia associated autosomal loci were associated with specific symptoms or cognitive domains. Case-only analysis using data from the Clinical Antipsychotics Trials of Intervention Effectiveness-Schizophrenia trials (n = 730). PRS was constructed using Psychiatric Genomics Consortium (PGC) leave one out genome wide association analysis as the discovery data set. For candidate region analysis, we selected 105-schizophrenia associated autosomal loci from the PGC study. We found a significant effect of PRS on positive symptoms at p-threshold (P T ) of 0.5 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at P T of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms.
Long-Term Factors Associated With Falls and Fractures Poststroke.

Background: Risk factors for poststroke falls and fractures remain poorly understood. This study aimed to evaluate which factors increased risk of these events after stroke. Methods: Data from 7,267 hospitalized stroke patients were acquired from the Norfolk and Norwich University Hospital Stroke Register from 2003-2015. The impacts of multiple patient level and stroke characteristics and comorbidities on post-discharge falls and fractures were assessed. Univariate and multivariable models were constructed, adjusting for multiple confounders, using binary logistic regression for short-term analysis (up to 1-year post-discharge) and Cox-proportional hazard models for longer term analysis (1-3, 3-5, and 0-10 years follow-up). Results: The mean age (SD) was 76.3 ± 12.1 years at baseline. 1,138 (15.7%) participants had an incident fall; and 666 (9.2%) an incident fracture during the 10-year follow-up (total person years = 64,447.99 for falls and 67,726.70 for fractures). Half of the sample population were females (50.6%) and the majority had an ischemic stroke (89.8%). After adjusting for confounders: age, sex, previous history of falls, and atrial fibrillation were associated with an increased risk of both falls and fractures during follow-up. Furthermore, chronic kidney disease and hyperlipidemia were associated with an increased risk of falls, while previous stroke/transient ischemic attack increased fracture risk. Total anterior circulation stroke and a prestroke modified Rankin Scale score of 3-5 were associated with decreased risk of both events, with hypertension and cancer decreasing risk of falls only. Conclusion: We identified demographic, stroke-related, and comorbid factors associated with poststroke falls and fracture incidence. Further studies are required to examine and establish the relationship between reversible factors and further explore the role of preventative measures to prevent poststroke falls and fractures.
Radiosurgery with 20 Gy provides better local contol of 1-3 brain metastases from breast cancer than with lower doses.

AIM: To determine the optimal dose of radiosurgery-alone for patients with 1-3 cerebral metastases from breast cancer. PATIENTS AND METHODS: Patients receiving 20 Gy (n=20) were compared to those receiving 16-18.5 Gy (n=10) for local control, distant brain control and overall survival. Seven other variables were also evaluated. RESULTS: Radiosurgery dose achieved significance on univariate (p=0.002; log-rank and Wilcoxon test) and multivariate analysis (p=0.004) of local control. Twelve-month local control rates were 94% after 20 Gy and 48% after 16-18.5 Gy. On univariate analysis of distant brain control, radiosurgery dose was not a significant factor, with 12-month rates of 73% and 60%, respectively. Regarding overall survival, radiosurgery dose was of borderline significance (p=0.059; Wilcoxon test). Twelve-month overall survival rates were 75% and 40%, respectively. On Cox regression analysis, radiosurgery dose exhibited a trend for improving survival (p=0.10). CONCLUSION: Radiosurgery with 20 Gy resulted in significantly better local control and led to a trend towards improved overall survival compared to treatment with 16-18.5 Gy.
Comparison of two dose levels of stereotactic radiosurgery for 1-3 brain metastases from non-small cell lung cancer.

AIM: Two dose groups of patients treated with stereotactic radiosurgery (SRS) alone for 1-3 brain metastases from non-small cell lung cancer (NSCLC) were compared for outcomes. PATIENTS AND METHODS: Based on the SRS dose administered to the margins of the brain lesions, 46 patients were assigned to groups treated with 15-18 Gy (n=13) or with 20 Gy (n=33). Seven additional factors were investigated: age (≤ 58 vs. ≥ 59 years), gender, Karnofsky performance score (KPS 70-80 vs. 90-100), number of brain metastases (1 vs. 2-3), histology (adenocarcinoma vs. other) extracerebral metastases and interval from NSCLC diagnosis to SRS (≤ 6 vs. >6 months). RESULTS: Local control rates for 15-18-Gy and 20-Gy groups were 75% and 92% at one year (p=0.043). SRS dose was significant on multivariate analysis (p=0.030). SRS dose was not associated with freedom from new brain metastases (p=0.24) or survival (p=0.37). CONCLUSION: SRS with 20 Gy resulted in better control of the irradiated metastases than 15-18 Gy did.
Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

BACKGROUND: An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. METHODS: Fifty-eight patients with 1-3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. RESULTS: The treatment regimen had no significant impact on local control in the univariate analysis (p=0.59). Age ≤59 years showed a trend towards improved local control on univariate (p=0.066) and multivariate analysis (p=0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p=0.040) and ECOG 0-1 (p=0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p=0.039) and performance status (p=0.028) maintained significance on multivariate analysis. ECOG 0-1 was positively correlated with survival on univariate analysis (p<0.001); age ≤59 years showed a strong trend (p=0.054). On multivariate analysis, performance status (p<0.001) and age (p=0.041) were significant. CONCLUSIONS: In breast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.
Radiotherapy beyond cancer: target localization in real-time MRI and treatment planning for cardiac radiosurgery.

PURPOSE: Atrial fibrillation (AFib) is the most common cardiac arrhythmia that affects millions of patients world-wide. AFib is usually treated with minimally invasive, time consuming catheter ablation techniques. While recently noninvasive radiosurgery to the pulmonary vein antrum (PVA) in the left atrium has been proposed for AFib treatment, precise target location during treatment is challenging due to complex respiratory and cardiac motion. A MRI linear accelerator (MRI-Linac) could solve the problems of motion tracking and compensation using real-time image guidance. In this study, the authors quantified target motion ranges on cardiac magnetic resonance imaging (MRI) and analyzed the dosimetric benefits of margin reduction assuming real-time motion compensation was applied. METHODS: For the imaging study, six human subjects underwent real-time cardiac MRI under free breathing. The target motion was analyzed retrospectively using a template matching algorithm. The planning study was conducted on a CT of an AFib patient with a centrally located esophagus undergoing catheter ablation, representing an ideal case for cardiac radiosurgery. The target definition was similar to the ablation lesions at the PVA created during catheter treatment. Safety margins of 0 mm (perfect tracking) to 8 mm (untracked respiratory motion) were added to the target, defining the planning target volume (PTV). For each margin, a 30 Gy single fraction IMRT plan was generated. Additionally, the influence of 1 and 3 T magnetic fields on the treatment beam delivery was simulated using Monte Carlo calculations to determine the dosimetric impact of MRI guidance for two different Linac positions. RESULTS: Real-time cardiac MRI showed mean respiratory target motion of 10.2 mm (superior-inferior), 2.4 mm (anterior-posterior), and 2 mm (left-right). The planning study showed that increasing safety margins to encompass untracked respiratory motion leads to overlapping structures even in the ideal scenario, compromising either normal tissue dose constraints or PTV coverage. The magnetic field caused a slight increase in the PTV dose with the in-line MRI-Linac configuration. CONCLUSIONS: The authors' results indicate that real-time tracking and motion compensation are mandatory for cardiac radiosurgery and MRI-guidance is feasible, opening the possibility of treating cardiac arrhythmia patients completely noninvasively.
A new prognostic instrument to predict the probability of developing new cerebral metastases after radiosurgery alone.

BACKGROUND: Addition of whole-brain irradiation (WBI) to radiosurgery for treatment of few cerebral metastases is controversial. This study aimed to create an instrument that estimates the probability of developing new cerebral metastases after radiosurgery to facilitate the decision regarding additional WBI. METHODS: Nine characteristics were investigated for associations with the development of new cerebral metastases including radiosurgery dose (dose equivalent to <20 Gy vs. 20 Gy vs. >20 Gy for tumor cell kill, prescribed to the 73-90% isodose level), age (≤60 vs. ≥61 years), gender, Eastern Cooperative Oncology Group performance score (0-1 vs. 2), primary tumor type (breast cancer vs. non-small lung cancer vs. malignant melanoma vs. others), number/size of cerebral metastases (1 lesion <15 mm vs. 1 lesion ≥15 mm vs. 2 or 3 lesions), location of the cerebral metastases (supratentorial alone vs. infratentorial ± supratentorial), extra-cerebra metastases (no vs. yes) and time between first diagnosis of the primary tumor and radiosurgery (≤15 vs. >15 months). RESULTS: Number of cerebral metastases (p = 0.002), primary tumor type (p = 0.10) and extra-cerebral metastases (p = 0.06) showed significant associations with development of new cerebral metastases or a trend, and were integrated into the predictive instrument. Scoring points were calculated from 6-months freedom from new cerebral metastases rates. Three groups were formed, group I (16-17 points, N = 47), group II (18-20 points, N = 120) and group III (21-22 points, N = 47). Six-month rates of freedom from new cerebral metastases were 36%, 65% and 80%, respectively (p < 0.001). Corresponding rates at 12 months were 27%, 44% and 71%, respectively. CONCLUSION: This new instrument enables the physician to estimate the probability of developing new cerebral metastases after radiosurgery alone. Patients of groups I and II appear good candidates for additional WBI in addition to radiosurgery, whereas patients of group III may not require WBI in addition to radiosurgery.
Comparison of 3D and 4D Monte Carlo optimization in robotic tracking stereotactic body radiotherapy of lung cancer.

PURPOSE: To investigate the adequacy of three-dimensional (3D) Monte Carlo (MC) optimization (3DMCO) and the potential of four-dimensional (4D) dose renormalization (4DMCrenorm) and optimization (4DMCO) for CyberKnife (Accuray Inc., Sunnyvale, CA) radiotherapy planning in lung cancer. MATERIALS AND METHODS: For 20 lung tumors, 3DMCO and 4DMCO plans were generated with planning target volume (PTV5 mm) = gross tumor volume (GTV) plus 5 mm, assuming 3 mm for tracking errors (PTV3 mm) and 2 mm for residual organ deformations. Three fractions of 60 Gy were prescribed to ≥ 95 % of the PTV5 mm. Each 3DMCO plan was recalculated by 4D MC dose calculation (4DMCrecal) to assess the dosimetric impact of organ deformations. The 4DMCrecal plans were renormalized (4DMCrenorm) to 95 % dose coverage of the PTV5 mm for comparisons with the 4DMCO plans. A 3DMCO plan was considered adequate if the 4DMCrecal plan showed ≥ 95 % of the PTV3 mm receiving 60 Gy and doses to other organs at risk (OARs) were below the limits. RESULTS: In seven lesions, 3DMCO was inadequate, providing < 95 % dose coverage to the PTV3 mm. Comparison of 4DMCrecal and 3DMCO plans showed that organ deformations resulted in lower OAR doses. Renormalizing the 4DMCrecal plans could produce OAR doses higher than the tolerances in some 4DMCrenorm plans. Dose conformity of the 4DMCrenorm plans was inferior to that of the 3DMCO and 4DMCO plans. The 4DMCO plans did not always achieve OAR dose reductions compared to 3DMCO and 4DMCrenorm plans. CONCLUSION: This study indicates that 3DMCO with 2 mm margins for organ deformations may be inadequate for Cyberknife-based lung stereotactic body radiotherapy (SBRT). Renormalizing the 4DMCrecal plans could produce degraded dose conformity and increased OAR doses; 4DMCO can resolve this problem.
Dose-escalation study for cardiac radiosurgery in a porcine model.

PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.
Stereotactic radiosurgery for newly diagnosed brain metastases: comparison of three dose levels.

BACKGROUND AND PURPOSE: Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. PATIENTS AND METHODS: In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months). RESULTS: For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79%, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95% confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis. CONCLUSION: SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose.