Takshan/R1 huggingface dataset:
Role of sleep duration and sleep-related problems in the metabolic syndrome among children and adolescents.

BACKGROUND: There is increasing recognition that sleep is a risk factor for metabolic syndrome (MetS). The aim of the present study was to analyze the relationship between self-reported sleep duration, sleep-related problems and the presence of MetS in children and adolescents from Bogotá, D.C., Colombia. METHODS: This is a cross-sectional analysis from the FUPRECOL study (2014-15). Participants included 2779 (54.2% girls) youth from Bogota (Colombia). MetS was defined as the presence of ≥3 of the metabolic abnormalities (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol [HDL-c], hypertension, and increased waist circumference) according to the criteria of de Ferranti/Magge and colleges. Self-reported sleep duration and sleep-related problems were assessed with the BEARS questionnaire. RESULTS: Logistic regression analysis showed that boys who meet recommended duration of sleep had a decreased risk of elevated blood glucose levels (Odds Ratio [OR] = 0.71, 95%CI [0.40-0.94]; p = 0.031) compared to boys who have short-long sleep duration. Also, compared to young without sleep problems, excessive sleepiness during the day was related to low HDL-c levels in boys (OR = 1.36, 95%CI [1.02-1.83]; p = 0.036) and high triglyceride levels in girls (OR = 1.28, 95%CI [1.01-1.63]; p = 0.045). Girls with irregular sleep patterns had decreased HDL-c levels (OR = 0.71, 95%CI [0.55-0.91]; p = 0.009). CONCLUSIONS: Recommended sleep duration was associated with a decreased risk of elevated fasting glucose levels in boys, and sleep problems was related to lower HDL-c in girls and higher triglyceride levels in boys. These findings suggested the clinical importance of improving sleep hygiene to reduce metabolic risk factors in children and adolescents.
The control of allergic rhinitis in real life: a multicenter cross-sectional Italian study.

Background: Allergic Rhinitis (AR) is a high-prevalence disease. In Europe about 25% of the general population is affected, and in Italy the prevalence is estimated to be 19.8%. The Allergic Rhinitis and its Impact on Asthma (ARIA) international document underlined that the prevalence of severe or refractory or overlapping rhinitis is increasing and represents a non-negligible socio-economic burden. In general, despite the social healthcare costs, allergic rhinitis remains underestimated, not sufficiently controlled and often undertreated. Aim of the study: In this multi-center Italian observational and prospective study we assessed the control of AR in patients (> 16 years) without previous asthma diagnosis, referred to Allergy Centers. Methods: Patients of both sexes and older than 16 with rhinitis symptoms and without asthma were studied. A Visual Analogue Scale (VAS) and the CARAT (Control of Allergic Rhinitis and Asthma Test) were used as patient reported outcome. The possible causes of poor control of AR, as per protocol, were assessed accordingly. Results: We observed 250 patients in a real-life setting: more than 60% of them had an uncontrolled AR, only about 50% used multiple medications, and only a minority were receiving allergen immunotherapy. Conclusion: This survey, conducted in a real-life setting, confirmed that AR is overall poorly controlled. The VAS assessment well correlates with the structured CARAT questionnaire and with the relevant symptoms of AR.
A national, multicenter, non-interventional, observational study on treatment patterns in patients with metastatic renal cell carcinoma in Turkey - NOTES study.

Introduction: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI. Patients and methods: To provide a first real-life data set in Turkey, we conducted a prospective, non-interventional, observational study and assessed the efficacy and safety of everolimus after two lines of treatment including interferon. A total of 100 patients with histologically confirmed mRCC were enrolled in the study from 11 centers between June 2012 and March 2014 (70 males and 30 females). Efficacy was assessed on the basis of progression-free survival and overall survival; safety of everolimus was assessed on the basis of adverse event occurrence. Results: The study results showed that the median progression-free survival with everolimus treatment was 8.1 months (95% CI: 5.1-11.1) and the median overall survival was 17.6 months (95% CI: 10.1-25.1), thus indicating a better overall response based on survival durations than those from the randomized Phase III REnal Cell cancer treatment with Oral RAD001 given Daily study results (4.9 and 14.8 months, respectively). Conclusion: The study showed that everolimus treatment is a safe and effective treatment option in the treatment of mRCC after VEGF-TKI, with an acceptable safety and tolerability profile in real-life settings.
Detection of mitochondrial DNA with 4977 bp deletion in leukocytes of patients with ischemic stroke.

BACKGROUND: Coronary artery disease is associated with a common mitochondrial DNA alteration, a 4977 bp deletion (mtDNA4977). The role of mtDNA4977 in ischemic stroke is unknown. METHODS: Real-time quantitative PCR was performed to quantify total mtDNA and mtDNA4977 in leukocytes in 283 ischemic stroke cases and 135 controls. Ratios of mtDNA4977 to total-mtDNA and total-mtDNA to nuclear-DNA were calculated. Nested PCR and Sanger sequencing were used to confirm undetectable levels of mtDNA4977. RESULTS: For 191 patients and 74 control subjects in the male group and 92 patients and 61 control subjects in the female group, there were no significant between-group differences in age, cholesterol level, body mass index, stroke severity, or 4977 deletion. After adjusting for confounding factors, there was no correlation between mtDNA4977 amount and infarction risk, recurrent stroke, or stroke severity. However, mtDNA4977 was undetected in 6.94% subjects, and these individuals had a higher prevalence of stroke than those with detectable mtDNA4977 (OR: 0.181, 95% CI 0.041-0.798, p = 0.024). Additionally, mtDNA4977 status had no effect on stroke prognosis, including stroke severity and recurrent stroke. CONCLUSION: In conclusion, there was no apparent association between mtDNA4977 deletion and cerebral infarction. Undetectable mtDNA4977 may be a marker or risk factor for ischemic stroke.
A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking.

PURPOSE: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. METHODS AND MATERIALS: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. RESULTS: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. CONCLUSIONS: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
A Survival Score for Patients Receiving Stereotactic Radiosurgery Alone for Brain Metastases from Breast Cancer.

AIM: To generate a survival score for patients with breast cancer treated with stereotactic radiosurgery (SRS) alone for brain metastases. PATIENTS AND METHODS: Seven factors were evaluated in 34 patients, namely age, performance score, number of brain metastases, maximum diameter of all brain metastases, location of brain metastases, extracerebral metastases and time between breast cancer diagnosis and SRS. The score was created from factors having a significant impact on survival. Points of 0 (worse survival) or 1 (better survival) were assigned. Factor scores were added to total prognostic scores for each patient. RESULTS: A significant impact on survival was found for performance score (p<0.001), maximum diameter of cerebral lesions (p=0.002), and extracerebral metastases (p=0.026). Three groups were designated by score: 0-1, 2 and 3 points. One-year survival rates were 48%, 71% and 100%, respectively (p<0.001). CONCLUSION: This score contributes to appropriate selection of personalized treatment in patients with breast cancer with few cerebral metastases.
Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C- reactive protein and hair cortisol sampled at the time of slaughter.

Background: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). Results: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having 'moderate' accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). Conclusion: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn.
Exploring fetal fibronectin testing as a predictor of labour onset: In parturient women from isolated communities.

OBJECTIVE: To investigate whether the fetal fibronectin assay would be useful for determining if a woman was close to a term delivery. If effective, this test would allow parturient women to stay in their communities longer. DESIGN: This feasibility study used a prospective cohort design to examine the negative predictive value of the fetal fibronectin test at term. SETTING: Iqaluit, NU. PARTICIPANTS: A total of 30 parturient women from rural and isolated communities in Nunavut. INTERVENTION: Starting at 36 weeks' gestation, women were tested every 2 days, and after 39 weeks this increased to every day until labour. MAIN OUTCOME MEASURES: The negative predictive value of the fetal fibronectin test was assessed. RESULTS: Women were no more likely to give birth at 7 or more days after their last negative fetal fibronectin test result relative to their likelihood of giving birth at 6 or fewer days after their last negative test result. Hence, the presence of fetal fibronectin in cervical secretion did not predict term delivery. CONCLUSION: This project indicated that the fetal fibronectin test did not have adequate sensitivity or specificity as a diagnostic measure to predict a delay of labour at term.
TECS: a toxin expression control strategy as a tool for optimization of inducible promoters.

BACKGROUND: Transcriptional control of gene expression is a widely utilized regulatory mechanism in synthetic biology, biotechnology and recombinant protein production. It is achieved by utilization of naturally occurring promoters responding to nutrients or chemicals. Despite their regulatory properties, these promoters often possess features which diminish their utility for biotechnology. High basal expression level and low induction ratio can be removed using genetic engineering techniques, although this process is often laborious and time-consuming. RESULTS: In order to facilitate optimization process for inducible promoters, we developed a simple method based on a conditional toxin expression which we abbreviate as toxin expression control strategy (TECS). In the presence of sucrose, SacB enzyme from Bacillus subtilis synthesizes levans which cause Eschericha coli cell lysis. However, in the absence of sucrose the enzyme does not affect the growth of the host. We utilized this feature to develop a two-step protocol allowing for efficient selection of inducible promoter variants. Using TECS we were able to modify the well-described pBAD promoter to decrease its leakage while maintaining high activity upon induction. Furthermore, we used the method to test transcriptional interference of lambda phage-derived sequence and optimize it for higher induction levels through random mutagenesis. CONCLUSIONS: We show that TECS is an efficient tool for optimization and development of inducible promoter systems in E. coli. Our strategy is very effective in the selection of promoter variants with improved properties. Its simplicity and short hands-on time make it an attractive method to optimize existing promoters and to construct novel, engineered genetic elements which improve properties of an inducible promoter system.
Experience of a Tertiary-Level Urology Center in the Clinical Urological Events of Rare and Very Rare Incidence. I. Surgical Never Events: 1. Urological Wrong-Surgery Catastrophes and Disabling Complications.

Introduction: Surgical never events are preventable harmful non-intentional human errors. Urology is a common surgical specialty for their occurrence. Patients and Methods: A retrospective search of our center's data was done during the period 2006-2016 for surgical never events. Each included case was studied for the primary diagnosis, procedure, and subspecialty, never event type and timing, needed extra-interventions, urologist/procedure proportioning, outcomes, and possible underlying causes of the event. Results: Of more than 55,000 different urological interventions, 61 patients were involved in never events. Wrong procedures represented 75% of the never events, and endourology and urolithiasis subspecialties were more often involved. The main detectable underlying factor was the disproportion between the levels of the procedure class and the qualification of the urologist (41%). Thirty-four cases had extra-procedures. The short-term harm effect represented the final outcome in 42% of all events. Death, permanent organ loss, and long-term harm represented 20, 15, and 23%, respectively. Conclusion: Urological surgical never events are rare, but their final outcomes could be catastrophic, even leading to death.
White Matter Damage in 4,725 Term-Born Infants Is Determined by Head Circumference at Birth: The Missing Link.

Background: White matter damage (WMD) is a prime risk factor for cerebral palsy, in part occurring unexplained. Though primarily a problem of preterm infants, there is growing evidence that in large newborns cephalopelvic disproportion and prolonged labor are involved. Objective: To explore both incidence of and morphometric risk factors for WMD in term-born infants. Study Design: We related growth variables and risk factors of term-born infants to WMD (61/4,725) using odds ratios of z-score bands. Results: The key result is the novel observation that head circumference is a prime and unique index for WMD in term-born neonates over the whole range of centiles (U-shaped; WMD (%) = 3.1168-0.12797∗HC (centile) + 0.0014741∗HC2; p < 0.0001). This suggests different mechanisms for WMD in the lowest and highest z-score band. In the latter, cephalic pressure gradients and prolonged labor with preserved neonatal vitality prevail, whereas in the previous one, acute and chronic oxygen deprivation with reduced vitality predominate. Conclusions: The fact that seemingly healthy term-born neonates are not screened by head imaging, in spite of both large head circumference and prolonged labor, is considered to be the missing link between the insult that escapes diagnosis and the development of unexplained developmental delay and cerebral palsy in childhood.
Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases.

PURPOSE: Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring. METHODS AND MATERIALS: We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression. RESULTS: Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model. CONCLUSIONS: Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.
Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes.

Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models. We identified high and low NE subtypes of SCLC in all of our sample types, and characterized their properties. Results: We found that 16% of human SCLC tumors and 10% of SCLC cell lines were of the low NE subtype, as well as cell lines from the GEM model. High NE SCLC lines grew as non-adherent floating aggregates or spheroids while Low NE lines had morphologic features of the variant subtype and grew as loosely attached cells. While the high NE subtype expressed one of the NE lineage master transcription factors ASCL1 or NEUROD1, together with NKX2-1, the entire range of NE markers, and lacked expression of the neuronal and NE repressor REST, the low NE subtype had lost expression of most NE markers, ASCL1, NEUROD1 and NKX2-1 and expressed REST. The low NE subtype had undergone epithelial mesenchymal transition (EMT) and had activated the Notch, Hippo and TGFβ pathways and MYC oncogene . Importantly, the high and low NE group of SCLC lines had similar gene expression profiles as their SCLC tumor counterparts. Conclusions: SCLC tumors and cell lines can exhibit distinct inter-tumor heterogeneity with respect to expression of NE features. Loss of NE expression results in major alterations in morphology, growth characteristics, and molecular properties. These findings have major clinical implications as the two subtypes are predicted to have very different responses to targeted therapies.
[Women's sexual life quality assessment with use of questionnaires in clinical trials--review of accessible tools, their characteristics and comparison of their properties].

Ocena jakości zycia seksualnego kobiet w badaniach klinicznych, przy uzyciu kwestionariuszy--przeglad dostepnych narzedzi, ich charakterystyka i porównanie właściwości. AIM: Aim of the study is a review of women's sexual life quality assessment questionnaires available in literature, analysis of their construction, special properties and usability in clinical trials. MATERIAL AND METHODS: Medline database and accessible literature has been reviewed. Seven questionnaires have been chosen for analysis. Analysis in scope of potential and usability of those questionnaires in clinical tests has been performed. CONCLUSIONS: Suitability of The Female Sexual Function Index (FSFI) and The Brief Index of Sexual Functioning for Women (BISF-W) have been shown as universal tools for sexual function assessment in clinical trials. They meet current model of women's sexual reaction and criteria of sexual disfunction classification.