Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond “Median Waiting Time”: Development and Validation of a Competing Risk Model to Predict Outcomes on the Kidney Transplant Waiting List

Background Median historical time to kidney transplant is misleading because it does not convey the competing risks of death or removal from the waiting list. We developed and validated a competing risk model to calculate likelihood of outcomes for kidney transplant candidates and demonstrate how this information differs from median time to transplant. Methods Data were obtained from the US Scientific Registry of Transplant Recipients. The retrospective cohort included 163 636 adults listed for kidney transplant before December 31, 2011. Predictors were age, sex, blood type, calculated panel-reactive antibodies, donation service area, dialysis duration, comorbid conditions, and body mass index. Outcomes were deceased or living donor transplant, death or removal from the list due to deteriorating medical condition, or removal due to other reasons. We calculated hazards for the possible outcomes, then the cumulative incidence function for a given candidate using competing risk methodology. Discrimination and calibration were assessed through C statistics and calibration plots for each cause-specific Cox proportional hazard model. Results C statistics ranged from 0.64 to 0.73. Calibration plots showed good calibration. The competing risk model shows probability of all possible outcomes for up to 12 years given a candidate's characteristics, contrasted with the median waiting time for that candidate's donation service area. Conclusions A competing risk model conveys more relevant information than the median waiting time for a given transplant center. This model will be updated to create a calculator reflecting the most recent outcomes and changes in allocation policy. It illustrates the conversations that should be initiated with transplant candidates.
A 30-year experience in using oral methotrexate as initial treatment for gestational trophoblastic neoplasia regardless of risk group

Background. Treatment of postmolar gestational trophoblastic neoplasia (GTN) is often stratified according to FIGO score using methotrexate (MTX) for low-risk patients and first-line multi-agent chemotherapy (e.g. EMA-CO) for high-risk patients. In contrast, oral MTX may be given as first-line therapy to all GTN patients regardless of risk group. The aim was to examine the efficacy of oral MTX and a response-adapted treatment policy, which has been used for three decades at Aarhus University Hospital (AUH). Material and methods. Seventy-one consecutive postmolar GTN patients treated 1981–2011 were included. Data were obtained from medical records, using histopathology and human choriogonadotropin (hCG) to verify the diagnosis. All patients received oral MTX as first-line chemotherapy. Second- and third-line chemotherapy was given according to response. Results. Sixty-four (90%) patients were retrospectively categorized as FIGO low-risk disease, whereas seven patients (10%) had high-risk disease. Complete response to first-line oral MTX chemotherapy was observed in 35/71 (49%) patients, while 62/71 (87%) had complete remission on MTX (first-line) and/or MTX plus dactinomycin (second-line), without the use of multi-agent therapy. Nine patients (13%) received third-line multi-agent chemotherapy, six low-risk (67%) and three high-risk (33%) patients. There were no recurrences and no patients died as a consequence of toxicity or disease. Conclusion. Fifty percent of all patients can be cured on oral MTX alone. By adding dactinomycin, about 90% are cured without use of multi-agent chemotherapy. The use of oral MTX as initial treatment can minimize the number of patients receiving multi-agent chemotherapy.
Fracture epidemiology in male elite football players from 2001 to 2013: ‘How long will this fracture keep me out?’

Background Determining fracture risk and rehabilitation periods after specific fractures in professional football is essential for team planning. Aim To identify fracture epidemiology and absences after different types of fractures in male professional football players. Methods 2439 players from 41 professional male teams in 10 countries were followed prospectively from 2001 to 2013. Team medical staff registered fractures, absences after fractures and player exposure. Results 364 fractures were recorded, with an incidence of 0.27/1000 h of exposure (95% CI 0.25 to 0.30). The incidence of traumatic fractures was 0.25 (0.22 to 0.27) and that of stress fractures was 0.03 (0.02 to 0.04). 45% of traumatic fractures and 86% of stress fractures affected the lower extremities. Absence after a fracture was 32 days (1–278) (median (range)), compared to that after a traumatic fracture of 30 days (1–278) and a stress fracture of 65 days (6–168) (p<0.001). Annual fracture incidence was stable during the study period (R2=0.051, b=−0.011 (95% CI −0.043 to 0.021)). Young players had a relative risk of 10.9 (3.3 to 35.6) of sustaining stress fractures compared to old players (p<0.01). The fracture incidence did not differ between individuals in different playing positions (p=0.10). Summary A male professional football team can expect 1 to 2 fractures per season. There are more traumatic fractures than stress fractures; while most fractures affect the lower extremities, stress fractures yield longer absences than traumatic fractures and young players have more stress fractures than old players. There is no difference in risk among players at different playing positions.
Imminent Concerns Of Filial Caregivers Reporting Recent Experiences Of Crisis

The purpose of this descriptive study was to generate information about imminent concerns of adult children that could serve as initial context for development of a meaningful framework for coping with an ongoing parent care situation. Ninety-two adult children pre-selected for self-reports of crisis were interviewed about their concerns and goals for caregiving and asked to discuss experiences of crisis in the previous six months of caregiving. Key issues pertaining to their experiences were extracted from notes of the interviews and classified according to their common properties. Cohen's kappa for interrater reliability of the classifications was . 79 while percentage agreement was 98 percent. The results of the study point to the presence of multiple issues pertaining to significant life and death events, relational burdens, early experiences with the family of origin, and focal patterns of distress and coping. Synthesis of the findings reveals overriding concerns for making improvements in one's family of origin, created family of adulthood, and middle-aged self. Findings have implications for experiential adult education in the area of filial maturity and caregiving.
Women’s Representation in Politics: Voter Bias, Party Bias, and Electoral Systems

We study how electoral systems affect the presence of women in politics using a model in which both voters and parties might have a gender bias. We apply the model to Spanish municipal elections, in which national law mandates that municipalities follow one of two different electoral systems: a closed-list system in which voters pick one party-list, or an open-list system, in which voters pick individual candidates. Using a regression discontinuity design, we find that the closed-list system increases the share of women among candidates and councilors by 2.5 percentage points, and the share of women among mayors by 4.3 percentage points. Our model explains these results as mostly driven by voter bias against women. We provide evidence that supports the mechanism of the model. In particular, we show that, when two councilors almost tied in general-election votes, the one with “one more vote�? is substantially more likely to be appointed mayor, but this does not happen when the most voted was female and the second was male, suggesting the presence of some voter bias. We also show that, in a subsample of municipalities with low bias — proxied by having had a female mayor in the past — the difference between the two electoral systems disappears.
Audit fees and financial crisis: Evidence from the spanish manufacturing industries

The international financial crisis plunged the Spanish economy in a downturn spiral from 2008 to 2010, with seven consecutives recession periods. During this period, Spanish companies faced growth and liquidity problems and credit constrains, which increased their business risk. The international literature emphasizes that there is a relationship between business risk and audit fees. This study considers if there is a relationship between time (the three years period when Spanish recession was higher and the following three-year period) and audit fees. We analyzed the financial statements and annual audit fees, obtained from SABI database, from 2008 to 2013, charged by auditors to 119 manufacturing companies. The results obtained, despite positive and negative correlations between audit fees and other variables of our model, are not totally conclusive neither consistent. They point out to a tenuous relationship between time and audit fees, partially corroborating the American reality, but not the studies made in Australia, China, Sweden and South Korea.
The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

SUMMARY The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp. , with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply “innocent bystanders” in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy.
[Guidelines of clinical practice of the SERV: treatment of exudative age-related macular degeneration (AMD)].

OBJECTIVE Age related macular degeneration (ARMD) in its neovascular form is a serious disease which produces legal blindness in many patients with poor prognosis if left untreated. We intend to establish a clinical guide with the different therapeutic options that exist nowadays, which may help the ophthalmologists in their clinical practice. METHODS A group of medical retina experts selected by SERV have evaluated the results of different published studies with the drugs currently available, obtaining an evidence-based consensus. Some recommendations have been established for diagnosis, treatment and monitoring of patients with neovascular ARMD. RESULTS The intravitreal injection of ranibizumab at a dosage of 0.5 mg produces significant improvement of visual acuity in subfoveal lesions, according to data obtained from studies with the highest level of evidence. It should be considered as a first choice drug. The use of bevacizumab, a drug with not approved indication for intraocular use, nor for the treatment of neovascular ARMD can reach a result which is closer to the ones obtained with ranibizumab than to those obtained with photodynamic therapy (PDT) and pegaptanib. The use of intravitreal pegaptanib sodium in intravitreal injection at a dosage of 0.3 mg as a treatment for subfoveal lesions can obtain similar results to the TFD, but with a wider range of injuries. CONCLUSION The results of the evidence-based studies are a good guide for the treatment of this disease.
Towards an EEG-based intelligent wheelchair driving system with vibro-tactile stimuli

Nowadays, the electroencephalography (EEG)-based wheelchair driving system, one of the major applications of brain-computer interface (BCI), that allows an individual with mobility impairments to perform daily living activities independently. In this context, user's intention identifying methods were developed by several research groups using various paradigms for the wheelchair driving. In this study, we use a steady-state somatosensory evoked potential (SSSEP) paradigm, which elicits brain responses to vibro-tactile stimulation of specific frequencies, for a user's intention identification to driving a wheelchair. The main focus of this study is to validate an effectiveness of our SSSEP-based wheelchair driving system via an online experiment with more challenging tasks than our recent study. In our system, a subject concentrated on one of vibro-tactile stimuli (attached on left-hand, right-hand, and foot) selectively for driving wheelchair (corresponding to turn-left, turn-right, and move-forward). Five healthy subjects participated in the online experiment, and the experimental results show that our SSSEP paradigm is suitable to EEG-based intelligent wheelchair driving system.
C/D-box snoRNA-derived RNA production is associated with malignant transformation and metastatic progression in prostate cancer

Small nucleolar RNAs (snoRNAs) are dynamically regulated in different tissues and affected in disease. SnoRNAs are processed further to stable smaller RNAs. We sequenced the small RNA transcriptome of prostate cancer (PCa) at different PCa stages and generated a quantified catalogue of 3927 small non-coding RNAs (sncRNAs) detected in normal and malignant prostate tissue. From these, only 1524 are microRNAs. The remaining 2401 sncRNAs represent stable sncRNAs species that originate from snoRNA, tRNA and other sncRNAs. We show that snoRNA-derived RNAs (sdRNAs) display stronger differential expression than microRNAs and are massively upregulated in PCa. SdRNAs account for at least one third of all small RNAs with expression changes in tumor compared to normal adjacent tissue. Multiple sdRNAs can be produced from one snoRNA in a manner related to the conservation of structural snoRNA motifs. Q-PCR analysis in an independent patient cohort (n=106) confirmed the processing patterns of selected snoRNAs (SNORD44, SNORD78, SNORD74 and SNORD81) and the cancer-associated up-regulation of their sdRNAs observed in sequencing data. Importantly, expression of SNORD78 and its sdRNA is significantly higher in a subset of patients that developed metastatic disease demonstrating that snoRNA and sdRNAs may present as novel diagnostic and/or prognostic biomarkers for PCa.
Local Radiotherapy Affects Drug Pharmacokinetics—Exploration of a Neglected but Significant Uncertainty of Cancer Therapy

Purpose: Concurrent chemoradiation therapy is the mainstay of treatment for many types of malignancies. However, concurrent chemoradiation therapy is associated with a greater number of systemic adverse effects than radiotherapy or chemotherapy alone. Summary: Pharmacokinetics is the study of a drug and/or its metabolite kinetics in the body, including absorption, distribution, metabolism, and elimination. The incidences of adverse effects are markedly higher in patients who receive concurrent chemoradiation therapy than in those who receive either radiotherapy or chemotherapy alone. This phenomenon implies that irradiation affects the pharmacokinetics of cytotoxic agents, namely the radiotherapy–pharmacokinetic phenomenon. Experimental animal studies have shown that local irradiation affects the systemic pharmacokinetics of 5-fluorouracil and cisplatin at both low dose (simulating generous dose distributed to normal tissues) and daily practice dose (mimicking therapeutic dose to target volumes). These effects are significant in the circulation of blood and lymphatic system as well as in the hepatobiliary excretion. Furthermore, recent studies have demonstrated that matrix metalloproteinase-8 plays an important role in the radiotherapy–pharmacokinetic phenomenon. Conclusion: In the present review, we provide a general overview of the radiotherapy–pharmacokinetic phenomenon and discuss the possible mechanisms governing the phenomenon.
Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas

Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor‐κB (NF‐κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF‐κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL.
Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant‐negative mechanism

Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol‐sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C‐terminal truncation that has been characterised previously as a dominant‐negative protein. G509V exhibits vesicular localisation identical to the wild‐type protein, but the C‐terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant‐negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant‐negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant‐negative function. Developmental Dynamics 229:780–790, 2004. © 2004 Wiley‐Liss, Inc.
Yap7 is a transcriptional repressor of nitric oxide oxidase in yeasts, which arose from neofunctionalization after whole genome duplication

Flavohemoglobins are the main detoxifiers of nitric oxide (NO) in bacteria and fungi and are induced in response to nitrosative stress. In fungi, the flavohemoglobin encoding gene YHB1 is positively regulated by transcription factors which are activated upon NO exposure. In this study, we show that in the model yeast Saccharomyces cerevisiae and in the human pathogen Candida glabrata, the transcription factor Yap7 constitutively represses YHB1 by binding its promoter. Consequently, YAP7 deletion conferred high NO resistance to the cells. Co‐immunoprecipitation experiments and mutant analyses indicated that Yap7 represses YHB1 by recruiting the transcriptional repressor Tup1. In S. cerevisiae, YHB1 repression also involves interaction of Yap7 with the Hap2/3/5 complex through a conserved Hap4‐like‐bZIP domain, but this interaction has been lost in C. glabrata. The evolutionary origin of this regulation was investigated by functional analyses of Yap7 and of its paralogue Yap5 in different yeast species. These analyses indicated that the negative regulation of YHB1 by Yap7 arose by neofunctionalization after the whole genome duplication which led to the C. glabrata and S. cerevisiae extant species. This work describes a new aspect of the regulation of fungal nitric oxidase and provides detailed insights into its functioning and evolution.
Diverse protective roles of the actin cytoskeleton during oxidative stress

Actin oxidation is known to result in changes in cytoskeleton organization and dynamics. Actin oxidation is clinically relevant since it occurs in the erythrocytes of sickle cell patients and may be the direct cause of the lack of morphological plasticity observed in irreversibly sickled red blood cells (ISCs). During episodes of crisis, ISCs accumulate C284‐C373 intramolecularly disulfide bonded actin, which reduces actin filament dynamics. Actin cysteines 284 and 373 (285 and 374 in yeast) are conserved, suggesting that they play an important functional role. We have been investigating the physiological roles of these cysteines using the model eukaryote Saccharomyces cerevisiae in response to oxidative stress load. During acute oxidative stress, all of the F‐actin in wild‐type cells collapses into a few puncta that we call oxidation‐induced actin bodies (OABs). In contrast, during acute oxidative stress the actin cytoskeleton in Cys‐to‐Ala actin mutants remains polarized longer, OABs are slower to form, and the cells recover more slowly than wild‐type cells, suggesting that the OABs play a protective role. Live cell imaging revealed that OABs are large, immobile structures that contain actin‐binding proteins and that can form by the fusion of actin cortical patches. We propose that actin's C285 and C374 may help to protect the cell from oxidative stress arising from normal oxidative metabolism and contribute to the cell's general adaptive response to oxidative stress. © 2011 Wiley‐Liss, Inc.
Factors predicting the development of metabolic syndrome and type II diabetes against a background of hypertension

Background The metabolic syndrome (MetS), predicting coronary heart disease (CHD), is a compound of risk factors including diabetes, obesity and hypertension. The relationship between the development of MetS, diabetes and CHD in patients with established hypertension is unclear. We hypothesized that patients with hypertension developing MetS are at increased risk of type II diabetes and CHD compared with patients who do not develop MetS.