Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA mismatch repair in prostate cancer.

Identification of germline mutations associated with cancer susceptibility has led to the rational development of screening protocols and prevention strategies for patients with heritable syndromes or those at increased risk for developing cancer. As reported in Journal of Clinical Oncology, Raymond et al investigated several generations of a large cohort of DNA mismatch repair (MMR) mutation–positive Lynch syndrome families and discovered an increased risk of prostate cancer in the 4,127 male carriers evaluated, at a rate two-fold higher than that in the general population and slightly higher in those younger than 60 years of age. These findings not only have important clinical implications for screening but also highlight the role of DNA MMR in tumorigenesis. Normal cells rely on DNA repair processes to correct biosynthetic errors that occur during replication. Six MMR proteins are required for proper nucleotide mismatch repair: MSH2, MLH1, PMS1, PMS2, MSH6, and MLH3. These proteins function coordinately within biochemical complexes to recognize and repair single base-base mismatches or defective insertion-deletion loops (Fig 1A). Lynch syndrome is an autosomal-dominant disorder characterized by single-allele germline mutations of an MMR gene, most commonly MLH1, MSH2, MSH6, or PMS2. By definition, these germline mutations are present in all cells of affected patients; however, a second allelic hit in somatic cells within a particular tissue type (through mutation, loss of heterozygosity, or epigenetic
Tobacco advertising/promotions and adolescents’ smoking risk in Northern Africa

Background Comprehensive tobacco advertising/promotion bans are effective against adolescent smoking but many developing countries have implemented only partial bans. This study examines the association between advertising/promotions exposure and adolescent cigarette smoking risk in North Africa, and possible mediation of this association by parent and peer smoking. Methods Adolescent data (n=12 329) from the Global Youth Tobacco Survey were analyzed (Libya, 2007; Egypt, 2005; Morocco, 2006; Tunisia 2007; and Sudan, 2005). Current smoking (any cigarette use in the past 30 days) and never-smokers' initiation susceptibility (composite of openness to accepting a cigarette from a friend and intention to start smoking in the next year) outcomes were examined. Advertising/promotion exposures included media and in-person contacts. Weighted univariate, bivariate and multivariable analyses were conducted. Results Current smoking prevalence ranged from 5.6% (Egypt) to 15.3% (Tunisia) among boys, and 1.1% (Libya and Egypt) to 2.0% (Morocco and Sudan) among girls. Initiation susceptibility ranged from 14.1% (Sudan) to 25.0% (Tunisia) among boys, and from 13.3% (Sudan) to 15.0% (Libya) among girls. Ninety-eight percent of adolescents reported exposure to at least one type of advertising/promotion. In multivariable analyses adjusting for demographics, each type of advertising/promotion was significantly and positively associated with boys' current smoking status; most advertising/promotion exposure types were also positively associated with initiation susceptibility among boys and girls. Peer smoking only partially mediated these associations. Conclusions Tobacco advertising/promotion exposure was highly prevalent and associated with adolescents' smoking risk in these countries. The comprehensiveness and enforcement of advertising/promotion bans needs to be enhanced.
PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer.

PURPOSE Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. PATIENTS AND METHODS Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. RESULTS The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). CONCLUSION Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.
Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus

Diabetic retinopathy (DR) can lead to significant vision loss and blindness and has a particularly high prevalence in patients with type 1 diabetes (DM1). In this study, we investigate quantitative differences in optical coherence tomography angiography (OCTA) data between DM1 patients with no or mild signs of retinopathy and non‐diabetic subjects.
New therapeutic applications for the anticoagulant, activated protein C

Background: Activated protein C (APC) is derived from its precursor, protein C (PC). Originally thought to be synthesised exclusively by the liver, recent reports have shown that PC is also produced by endothelial cells, smooth muscle cells, keratinocytes and some leukocytes. Objective: To provide an update on the emerging therapeutic effects of APC. Results/conclusion: APC functions as an anticoagulant with cytoprotective, anti-inflammatory and antiapoptotic properties. In vitro and preclinical data have revealed that APC exerts its protective effects via an intriguing mechanism requiring endothelial protein C receptor and protease activated receptor-1. Approved as a therapeutic agent for severe sepsis, APC is emerging as a potential treatment for a number of autoimmune and inflammatory diseases including spinal cord injury, asthma, chronic wounds and possibly rheumatoid arthritis. The future therapeutic uses of APC look very promising.
MR imaging of multiple myeloma patients with bone-marrow transplants

Purpose: to evaluate the role of MR imaging in the examination of multiple myeloma (MM) patients with bone-marrow transplants Material and Methods: A total of 40 MR examinations were made of 20 patients: 33 examinations of the spine and pelvis in 20/20 patients; and 7 examinations of the femora in 5/20 patients. the 40 examinations were evaluated and the results compared with those found at radiography. Altogether 13/20 patients were re-examined: 10 after 1 year (1 patient twice); and 3 after 2 years. Five sequences were tested, 3 of them first without and then with i.v. contrast enhancement Results: in 24/33 examinations, active MM lesions were shown by MR. in 16/33 examinations, MR showed greater spread and detectability than radiography. in the 5/20 femoral patients, 3 had a peripheral red bone-marrow extension in the femora. in the 13 re-examinations, the lesions had spread in 4 patients, were unchanged in 7, and had decreased in 2. the lesions were easier to detect with the turbo inversion recovery (TIR) technique and with fat saturation than with the conventional spin-echo sequences. Contrast enhancement made the lesions more conspicuous in 8/17 examinations Conclusion: MR has the potential to be a useful routine examination with T1-weighted and TIR sequences of selected areas, and without the use of contrast enhancement. However, further longitudinal studies are necessary in order to evaluate its possible predictive value
Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial.

PURPOSE Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. PATIENTS AND METHODS Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4). RESULTS Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS. CONCLUSION Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.
Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation

Objectives To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. Design Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. Setting Eight acute NHS hospital trusts and 12 local authority areas in North East England. Participants 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. Interventions A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. Main outcome measures Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. Results After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. Conclusions The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery.
Is diurnal lifestyle altered during Ramadan in professional Muslim athletes?

Lifestyle and circadian patterns are disturbed in Muslims during the holy month of Ramadan. The aims of this study were to establish how the timing of sleep was influenced by fasting diurnal requirements and how training practices were altered in professional soccer players by comparing behaviour over the Ramadan month to that displayed in the four weeks immediately following. Altogether 20 players from a top professional club in an Islamic country were monitored for eight weeks. Environmental conditions were similar between the two periods. The players adjusted to the privations of Ramadan by altering bedtime to later at night and spending longer in bed than in the month following. Timing of sleep was delayed significantly during Ramadan, a mean delay in bedtime (199 ± 47 min) and an increase in sleep length (99 ± 42 min) being observed during Ramadan. The training load, as indicated by training impulse (TRIMP) scores, did not vary between Ramadan and the following four weeks, although the duration of training sessions was shortened after two weeks of Ramadan. Core temperature responses (38.4 ± 0.6 and 38.5 ± 0.7°C) to training and fluid losses were similar between the two four-week periods. Fluid intake (r = 0.81; P < 0.05) and fluid loss (R = 0.76; P < 0.05) were significantly correlated with TRIMP scores. Urine osmolality (825 ± 143 mOsmol/kg H2O) was higher during Ramadan compared to the reference period that followed (708 ± 155 mOsmol/kg H2O); there was also a significant difference during the weeks of Ramadan (F 3,27 = 3.42; P < 0.05), pair-wise comparisons revealing a significant difference (P = 0.038) between week 1 and week 4, a mean reduction of 159 mOsmol/kg H2O. The results demonstrate how these players responded to the fasting requirements of Ramadan and cannot be generalised to non-professional athletes or individuals adopting more devout programmes.
Endocarditis prophylaxis and congenital heart defects in the Norwegian Public Dental Service

The aims of this study are (i) to assess how dental health workers of the Public Dental Service, PDS, carry out endocarditis prophylaxis related to dental treatment for children and adolescents with congenital heart defects (CHD) and to identify factors influencing their appropriate use of guidelines and (ii) to assess how dental health workers perceive any characteristics of patients with CHD.
Impact of the WHO FCTC over the first decade: a global evidence review prepared for the Impact Assessment Expert Group

Objective To present findings of a narrative review on the implementation and effectiveness of 17 Articles of the WHO Framework Convention on Tobacco Control (FCTC) during the Treaty’s first decade. Data sources Published reports on global FCTC implementation; searches of four databases through June 2016; hand-search of publications/online resources; tobacco control experts. Study selection WHO Convention Secretariat global progress reports (2010, 2012, 2014); 2015 WHO report on the global tobacco epidemic; studies of social, behavioural, health, economic and/or environmental impacts of FCTC policies. Data extraction Progress in the implementation of 17 FCTC Articles was categorised (higher/intermediate/lower) by consensus. 128 studies were independently selected by multiple authors in consultation with experts. Data synthesis Implementation was highest for smoke-free laws, health warnings and education campaigns, youth access laws, and reporting/information exchange, and lowest for measures to counter industry interference, regulate tobacco product contents, promote alternative livelihoods and protect health/environment. Price/tax increases, comprehensive smoking and marketing bans, health warnings, and cessation treatment are associated with decreased tobacco consumption/health risks and increased quitting. Mass media campaigns and youth access laws prevent smoking initiation, decrease prevalence and promote cessation. There were few studies on the effectiveness of policies in several domains, including measures to prevent industry interference and regulate tobacco product contents. Conclusions The FCTC has increased the implementation of measures across several policy domains, and these implementations have resulted in measurable impacts on tobacco consumption, prevalence and other outcomes. However, FCTC implementation must be accelerated, and Parties need to meet all their Treaty obligations and consider measures that exceed minimum requirements.
Management of the Scapula in Glenohumeral Instability

The scapula is a pivotal element in normal scapulohumeral rhythm and glenohumeral stability. It helps to maintain normal glenohumeral angle and acts as a stable base for muscular origins. Scapular dyskinesis, or alterations in scapular position and motion in arm activity, is common in both traumatic and microtraumatic glenohumeral instability. The exact etiology of dyskinesis is not known, but the resulting biomechanical alterations increase glenohumeral angulation, increase tensile strain in the glenohumeral ligaments, and decrease rotator cuff activation. These two actions increase the dysfunction associated with instability and decrease the effectiveness of treatment. Evaluation of scapular motion should be an integral part of the evaluation of the unstable shoulder, and restoration of normal scapulohumeral kinematics should accompany treatment and rehabilitation of the underlying instability.
Value of Differenf Markers in Cerebrospinal Fluid for Diagnostics of Creutzfeldt-Jakob Disease: Evaluation in Three Cases

Creutzfeldt-Jakob disease (CJD) is a very rare fatal neuronal disease with an incidence of about l: . Diagnosis of CJD is often very complicated and requires a great number of clinical and laboratory methods. Although prior studies have shown increased values of neuron-specific enolase (NSE), protein S100, protein tau, creatine kinase (CK-BB) and 14-3-3 protein in cerebrospinal fluid (CSF) of CJD patients, these markers have not been comparatively evaluated and repeated determinations over a longer observation time are often lacking. This study therefore compares the diagnostic value of these parameters in CSF of three CJD patients. Conventional parameters like cell number and morphology as well as CSF/serum-ratios of immunoglobulins were also determined. Concentrations of NSE, protein S-100 and protein tau were strongly increased, whereas CK-BB showed only slight variations and the results of the conventional CSF parameters were within the reference limits. In one of the three patients CSF analyses were performed four times within an observation time of three months. Concentrations of protein tau in CSF continuously increased, whereas concentrations of NSE and protein S100 did not. Although the number of investigated patients is very small the data obtained suggests that the determination of NSE, protein tau, protein S-100 and CK-BB can be a useful tool for supporting the diagnosis of Creutzfeldt-Jakob disease.
Staff-based measures of individualized care for persons with dementia in long-term care facilities

Although individualized care for persons with dementia in long-term care institutions has become accepted as best practice, there have not been easy-to-use, multi-item reliable measures of the concept for scientific research or for administrative use. Following review of the literature, consultation with experts in the field, and direct observation within long-term care facilities, three domains of individualized care (knowing the person/resident, resident autonomy and choice, communication — staff-to-staff and staff-to-resident) were chosen as appropriate for the development of multi-item paper-and-pencil staff completion scales. These scales are presented in this article, including, where appropriate, shorter scales derived from factor analyses. The findings suggest that these domains of individualized care lend themselves to brief multi-item measures and that not all conceptual domains of individualized care co-occur in practice. Further, supplemental staff training in individualized care practice may be warranted.
Effect of onartuzumab added to erlotinib on metastasis in patients with lung cancer.

TO THE EDITOR: A randomized phase II trial suggests improved outcome with the addition of onartuzumab to erlotinib in patients with advanced non–small-cell lung cancer (NSCLC) expressing MET. Overall survival (OS) is improved disproportionately in the combination arm compared with progression-free survival (PFS). Median OS improvement of 8.8 months compares with a 1.4-month improvement for median PFS, and response rates in both groups were low and not significantly different. In considering the current understanding of MET biology, the authors suggest that the therapeutic benefit of onartuzumab may arise from inhibition of migration and invasion rather than direct inhibition of tumor growth. Upregulation of oncogenic MET signaling results in features of epithelial to mesenchymal transition, including increased protease production, cell dissociation, and increased motility. This can contribute to cellular invasion through extracellular matrix, enabling tumor invasion and metastasis. In mouse models, silencing of endogenous overexpressed MET gene in tumor cells suppresses tumor growth and metastasis. Onartuzumab may have had a similar effect in the patients on this trial. We suggest that clinical support for this mechanism of action may be available in the data collected by Spigel et al. Review of computed tomography scans documenting progression could categorize patients according to increase in size of target lesions identified at baseline, or detection of new metastatic sites. If, compared with erlotinib controls, MET-positive patients who experience disease progression in the combination arm are less likely to have new distant metastases, indirect clinical support for their hypothesis would be provided. In addition, if confirmed, this finding would provide a possible explanation for the observed impressive survival benefit with the addition of onartuzumab to erlotinib, despite a low response rate and the absence of significant PFS difference seen with the combination. In an era of individualized treatment with expensive targeted therapies, early prediction of clinical benefit is of great value. However, current radiological tools, including response, may not be sufficient to evaluate the complex biology that underlies the mode of action of these drugs. The results presented by Spigel et al offer an exciting new perspective for patients with MET-positive NSCLC, but further exploration of the mode of disease progression, as suggested above, is warranted.