Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term outcomes of proton therapy for prostate cancer in Japan: a multi‐institutional survey of the Japanese Radiation Oncology Study Group

This is the first multi‐institutional retrospective survey of the long‐term outcomes of proton therapy (PT) for prostate cancer in Japan. This retrospective analysis comprised prostate cancer patients treated with PT at seven centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. Biochemical relapse was based on the Phoenix definition (nadir + 2.0 ng/mL). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. There were 215, 520, and 556 patients in the low‐risk, intermediate‐risk, and high‐risk groups, respectively. The median follow‐up period of surviving patients was 69 months (range: 7–107). Among all patients, 98.8% were treated using a conventional fractionation schedule and 1.2% with a hypofractionation schedule; 58.5% and 21.5% received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5‐year biochemical relapse‐free survival (bRFS) and overall survival rates in the low‐risk, intermediate‐risk, and high‐risk groups were 97.0%, 91.1%, and 83.1%, and 98.4%, 96.8%, and 95.2%, respectively. In the multivariate analysis, the NCCN classification was a significant prognostic factor for bRFS, but not overall survival. The incidence rates of grade 2 or more severe late gastrointestinal and genitourinary toxicities were 4.1% and 4.0%, retrospectively. This retrospective analysis of a multi‐institutional survey suggested that PT is effective and well‐tolerated for prostate cancer. Based on this result, a multi‐institutional prospective clinical trial (UMIN000025453) on PT for prostate cancer has just been initiated in order to define its role in Japan.
Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation and overactivation of the complement alternative pathway. Typically, gene analysis for aHUS and C3G is undertaken in small patient numbers, yet it is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, we performed a six-center analysis of 610 rare genetic variants in 13 mostly complement genes (CFH, CFI, CD46, C3, CFB, CFHR1, CFHR3, CFHR4, CFHR5, CFP, PLG, DGKE, and THBD) from >3500 patients with aHUS and C3G. We report 371 novel rare variants (RVs) for aHUS and 82 for C3G. Our new interactive Database of Complement Gene Variants was used to extract allele frequency data for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in five genes CFH, CFI, CD46, C3, and DGKE than in the Exome Aggregation Consortium (allele frequency < 0.01%), thus correlating these with aHUS. For C3G, an association was only found for RVs in C3 and the N-terminal C3b-binding or C-terminal nonsurface-associated regions of CFH. In conclusion, the RV analyses showed nonrandom distributions over the affected proteins, and different distributions were observed between aHUS and C3G that clarify their phenotypes.
Objective assessment of compliance with intra- and extraoral removable appliances.

OBJECTIVE To conduct an objective assessment of the level of compliance in young patients prescribed various types of removable appliances and to determine the influence of device type, treatment duration, and patient age, gender, psychological maturity, and awareness of monitoring on compliance. MATERIALS AND METHODS A total of 30 patients were fitted with either a class 2 (Frankel or bionator) or a class 3 (face mask) removable appliance, each bearing a compliance indicator chip, and they were instructed to wear them for 13 hours per day. Compliance was monitored by means of the sensor for an average of 8 months. Of the patients, 14 were informed that their appliance was fitted with a monitoring sensor, and 16 were not. The psychological maturity of all patients was assessed on the Nowicki-Strickland Locus of Control Scale, and the effect on compliance of this score as well as the patient- and treatment-related variables considered were determined via statistical analysis Results: The mean compliance recorded by the chips was 8.6 ± 2.9 hours, far lower than the 13 hours prescribed, and younger patients showed significantly greater compliance than adolescents (P < .01). However, no significant differences in compliance were found between intra- and extraoral appliances, and neither gender, psychological scores, treatment duration, nor awareness of being monitored had any significant effect. CONCLUSIONS Compliance is generally very poor in young patients, regardless of their gender and psychological maturity. Although awareness of monitoring does not appear to boost compliance, such systems may be a valuable means of providing a dentist with objective information regarding their patients' compliance.
The articular cavity washing with safflower injection combined with bearded needle debonding cure knee osteoarthritis

Objective:To investigate the clinical effectiveness of articular cavity washing with safflower injection combined with bearded needle debonding cure knee osteoarthritis.Methods:Seventy-eight patients with knee osteoarthritis were randomly divided into treatment group and control group with 39 patients each.Arthroscopy surgeries in the control group used normal saline as perfusate on knee cavities,while the treatment group adopted safflower injection with bearded needle debonding,which is widely adopted in clinical practice.Results:The treatment group showed average score was(89.250±13.236) after surgery,control group(66.750±12.250),there was statistical significance(P0.01). It indicate that significant effect of safflower perfusate washing in the treatment of knee osteoarthritis.Conclusion:The usage of safflower solution in treating knee osteoarthritis is proved effective,with effects in improving micro-circulation,reducing inflammation,assisting the recovery of articular cartilage and impaired synovial membrane.Combined with bearded needles,it helps debonding the parenchyma adhesion surrounding knee-joint,adjust the balancing of knee-joint to recover kinetic functions of the knees,and has significant and safe effects in reducing clinical symptoms.
Path-equivalent removals of ε-transitions in a genomic weighted finite automaton

Weighted finite automata (WFA) are used with accelerating hardware to scan large genomic banks. Hardwiring such automata raise surface area and clock frequency constraints, requiring efficient e-transitions-removal techniques. In this paper, we present new bounds on the number of new transitions for several e-transitions-removal problems. We study the case of acyclic WFA. We introduce a new problem, the partial removal of e-transitions while accepting short chains of e-transitions.
Automatic car driving detection using raw accelerometry data

Measuring physical activity using wearable devices has become increasingly popular. Raw data collected from such devices is usually summarized as ‘activity counts’, which combine information of human activity with environmental vibrations. Driving is a major sedentary activity that artificially increases the activity counts due to various car and body vibrations that are not connected to human movement. Thus, it has become increasingly important to identify periods of driving and quantify the bias induced by driving in activity counts. To address these problems, we propose a detection algorithm of driving via accelerometry (DADA), designed to detect time periods when an individual is driving a car. DADA is based on detection of vibrations generated by a moving vehicle and recorded by an accelerometer. The methodological approach is based on short-time Fourier transform (STFT) applied to the raw accelerometry data and identifies and focuses on frequency vibration ranges that are specific to car driving. We test the performance of DADA on data collected using wrist-worn ActiGraph devices in a controlled experiment conducted on 24 subjects. The median area under the receiver-operating characteristic curve (AUC) for predicting driving periods was 0.94, indicating an excellent performance of the algorithm. We also quantify the size of the bias induced by driving and obtain that per unit of time the activity counts generated by driving are, on average, 16% of the average activity counts generated during walking.
The consistency of the subjective concept of randomness

A pervasive bias in the subjective concept of randomness is that people often expect random sequences to exhibit more alternations than produced by genuine random processes. What is less known is the stability of this bias. Here, we examine two important aspects of the over-alternation bias: first, whether this bias is present in stimuli that vary across feature dimensions, sensory modalities, presentation modes and probing methods, and, second, how consistent the bias is across these stimulus variations. In Experiment 1, participants adjusted sequences until they looked maximally random. The sequences were presented as temporal streams of colors, shapes, auditory tones or tiled as spatial matrices. In Experiment 2, participants produced random matrices by adjusting the color of each cell. We replicated the findings using a within-subjects design in Experiment 3. We found that participants judged and produced over-alternating stimuli as the most random. Importantly, this bias was consistent across presentation modes (temporal vs spatial), feature dimensions (color vs shape), sensory modalities (visual vs auditory), speed (fast vs slow), stimulus size (small vs large matrices) and probing methods (adjusting the generating process vs individual bits). Overall, the results suggest that the subjective concept of randomness is highly stable across stimulus variations.
A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity

Background: High platelet reactivity (HPR) during clopidogrel treatment predicts postpercutaneous coronary intervention (PCI) ischemic events strongly and independently. Tongxinluo capsules (TCs) are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome (ACS) patients with HPR. Methods: This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2Y12 reaction units (PRUs) between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Results: Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction (15.8% vs. 24.8%, P = 0.013), especially among patients with one cytochrome P450 2C19 loss of function (LOF) allele (&khgr;2= 2.931, P = 0.047). The TC group also had a lower prevalence of HPR (33.3% vs. 54.2%, t = 5.284, P = 0.022) and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein (hsCRP), but the composite prevalence of ischemic events did not differ significantly (&khgr;2= 1.587, P = 0.208). Conclusions: In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.
Gene Expression Signature of Normal Cell-of-Origin Predicts Ovarian Tumor Outcomes

The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome.
A longitudinal study of cognitive decline in rural Tanzania: rates and potentially modifiable risk factors

ABSTRACT Background: The number of people living with dementia in sub-Saharan Africa (SSA) is expected to increase rapidly in the coming decades. However, our understanding of how best to reduce dementia risk in the population is very limited. As a first step in developing intervention strategies to manage dementia risk in this setting, we investigated rates of cognitive decline in a rural population in Tanzania and attempted to identify associated factors. Methods: The study was conducted in the rural Hai district of northern Tanzania. In 2014, community-dwelling people aged 65 years and over living in six villages were invited to take part in a cognitive screening program. All participants from four of the six villages were followed-up at two years and cognitive function re-tested. At baseline and follow-up, participants were assessed for functional disability, hypertension, and grip strength (as a measure of frailty). At follow-up, additional assessments of visual acuity, hearing impairment, tobacco and alcohol consumption, and clinical assessment for stroke were completed. Results: Baseline and follow-up data were available for 327 people. Fifty people had significant cognitive decline at two-year follow-up. Having no formal education, low grip strength at baseline, being female and having depression at follow-up were independently associated with cognitive decline. Conclusions: This is one of the first studies of cognitive decline conducted in SSA. Rates of decline at two years were relatively high. Future work should focus on identification of specific modifiable risk factors for cognitive decline with a view to developing culturally appropriate interventions.
Software engineering for the web: the state of the practice

Today’s web applications increasingly rely on client-side code execution. HTML is not just created on the server, but manipulated extensively within the browser through JavaScript code. In this paper, we seek to understand the software engineering implications of this. We look at deviations from many known best practices in such areas of performance, accessibility, and correct structuring of HTML documents. Furthermore, we assess to what extent such deviations manifest themselves through client-side code manipulation only. To answer these questions, we conducted a large scale experiment, involving automated client-enabled crawling of over 4000 web applications, resulting in over 100,000,000 pages analyzed, and close to 1,000,000 unique client-side user interface states. Our findings show that the majority of sites contain a substantial number of problems, making sites unnecessarily slow, inaccessible for the visually impaired, and with layout that is unpredictable due to errors in the dynamically modified DOM trees.
ODoSE: A Webserver for Genome-Wide Calculation of Adaptive Divergence in Prokaryotes

Quantifying patterns of adaptive divergence between taxa is a major goal in the comparative and evolutionary study of prokaryote genomes. When applied appropriately, the McDonald-Kreitman (MK) test is a powerful test of selection based on the relative frequency of non-synonymous and synonymous substitutions between species compared to non-synonymous and synonymous polymorphisms within species. The webserver ODoSE (Ortholog Direction of Selection Engine) allows the calculation of a novel extension of the MK test, the Direction of Selection (DoS) statistic, as well as the calculation of a weighted-average Neutrality Index (NI) statistic for the entire core genome, allowing for systematic analysis of the evolutionary forces shaping core genome divergence in prokaryotes. ODoSE is hosted in a Galaxy environment, which makes it easy to use and amenable to customization and is freely available at www.odose. nl.
Depression and frailty in later life: a systematic review

Frailty and depression are important issues affecting older adults. Depressive syndrome may be difficult to clinically disambiguate from frailty in advanced old age. Current reviews on the topic include studies with wide methodological variation. This review examined the published literature on cross-sectional and longitudinal associations between frailty and depressive symptomatology with either syndrome as the outcome, moderators of this relationship, construct overlap, and related medical and behavioral interventions. Prevalence of both was reported. A systematic review of studies published from 2000 to 2015 was conducted in PubMed, the Cochrane Database of Systematic Reviews, and PsychInfo. Key search terms were “frailty”, “frail”, “frail elderly”, “depressive”, “depressive disorder”, and “depression”. Participants of included studies were ≥55 years old and community dwelling. Included studies used an explicit biological definition of frailty based on Fried et al’s criteria and a screening measure to identify depressive symptomatology. Fourteen studies met the inclusion/exclusion criteria. The prevalence of depressive symptomatology, frailty, or their co-occurrence was greater than 10% in older adults ≥55 years old, and these rates varied widely, but less in large epidemiological studies of incident frailty. The prospective relationship between depressive symptomatology and increased risk of incident frailty was robust, while the opposite relationship was less conclusive. The presence of comorbidities that interact with depressive symptomatology increased incident frailty risk. Measurement variability of depressive symptomatology and inclusion of older adults who are severely depressed, have cognitive impairment or dementia, or stroke may confound the frailty syndrome with single disease outcomes, accounting for a substantial proportion of shared variance in the syndromes. Further study is needed to identify medical and behavioral interventions for frailty and depressive symptomatology that prevent adverse sequelae such as falls, disability, and premature mortality.
Desensitization and Prevention of Antibody-Mediated Rejection in Vascularized Composite Allotransplantation by Syngeneic Hematopoietic Stem Cell Transplantation

Background Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection. Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent antibody-mediated rejection in VCA. Methods Skin transplants from Dark Agouti to Lewis rats were performed for sensitization. Orthotopic hind limb transplants from Dark Agouti donors were performed to sensitized and nonsensitized recipients, and the animals were treated with either daily tacrolimus or no immunosuppression. A desensitization protocol consisting of total body irradiation, fludarabine, and syngeneic HSCT was applied to sensitized animals. Graft rejection was monitored by clinical assessment and histological analysis. Serum levels of donor-specific antibodies (DSA IgG) were measured using flow cytometry. Results Sensitized recipients exhibited accelerated rejection by 5.5 ± 1.2 days without immunosuppression and 10.2 ± 3.6 days with daily tacrolimus compared with 8.7 ± 1.2 days and longer than 30 days in nonsensitized recipients, respectively. Serum levels of DSA IgG were markedly elevated (37.3 ± 3.34-fold from baseline) in sensitized recipients after VCA and correlated with histologic evidence of rejection and C4d deposition. Desensitization significantly reduced DSA compared with sensitized controls (2.6 ± 0.5-fold vs 6.0 ± 1.2-fold, P < 0.01) and along with daily tacrolimus led to improved VCA survival longer than 30 days without evidence of C4d deposition (n = 6). Conclusions In summary, sensitization leads to accelerated rejection of VCA, and syngeneic HSCT combined with conventional immunosuppression effectively reduces DSA and improves allograft survival in sensitized rats.
Ubiquitylation as a Rheostat for TCR Signaling: From Targeted Approaches Toward Global Profiling

T cell receptor (TCR) signaling must be precisely tuned to limit collateral damage and prevent reactivity to self, while still allowing robust protective immune responses that control pathogen invasion. One process that can be used to promote, modify, or terminate TCR signaling is ubiquitylation. During ubiquitylation, ubiquitin is covalently attached to target proteins through a multistep process, in which E3 ubiquitin ligases promote the formation of ubiquitin chains on selected substrates. Ubiquitylation can facilitate protein–protein interactions, direct a protein to a specific subcellular location, or initiate protein destruction. Like phosphorylation, ubiquitylation is a reversible process – deubiquitylating enzymes counteract ligase function by removing ubiquitin chains. This reversibility also allows for ubiquitin chain “editing. ” Based on an emerging wealth of information from genetic loss-of-function studies showing that deregulation of ubiquitylation pathways leads to immune dysfunction, it has become increasingly apparent that the dynamic process of ubiquitylation is critical for normal immune cell function. In this review, we will describe how ubiquitylation acts as a key modulator and integrator of signaling downstream of TCR engagement. Specifically, we highlight the known roles of the substrate-specific E3 ligases and deubiquitylating enzymes in TCR signaling and T cell activation. While it is clear that ubiquitin enzymes tune T cell signaling and T cell function, elucidating the molecular mechanisms by which these proteins modulate T cells has met with significant challenges. Identifying substrates of these enzymes has been a particular challenge, and thus substrates of many E3 ligases and deubiquitylating enzymes remain largely unknown. To that end, we discuss the promise, and some practical considerations, of using proteomics-based techniques for unbiased identification of putative substrates of ubiquitin cascade proteins within primary T cells. These methods provide an exciting opportunity for further defining how TCR signals are regulated and for identifying new targets for therapeutic modulation.