Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified.
Plasma concentrations of angiopoietin-1, angiopoietin-2 and Tie-2 in colon cancer.

BACKGROUND/AIM despite the rapidly accumulating histopathological data reporting differences in the expression of members of the angiopoietin family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including colon cancer, are scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in colon cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor. PATIENTS AND METHODS the study cohort included 36 patients (18 male, 18 female) with colon cancer (mean age 52.6 ± 15.0), and 36 sex- and age-matched, healthy controls who were free of inflammatory, neoplastic, atherosclerotic and connective tissue disease, recruited from hospital staff and attendees at hospital for check-up. Concentrations of Ang-1, Ang-2 and Tie-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS concentrations of Ang-2 (median 3,188.0 pg/mL, min: 1,070.5-max: 5,765.5) and Tie-2 (median 22 ng/mL, min:12-max:46) were significantly higher in patients with colon cancer, while concentrations of Ang-1 were not statistically different between the groups. Furthermore, concentrations of Ang-2 (median 4,292.0 pg/mL, min: 3,090.0-max: 5,765.5) were found to be significantly higher in stage III patients compared to stage II patients, whereas no difference was found between the concentrations of Ang-1 and Tie-2 in different colon cancer stages. CONCLUSION plasma concentrations of Ang-1, Ang-2 and Tie-2 may be valuable, additional, tumor markers in colon cancer that should be tested in further trials.
Telomere Length and Breast Cancer Prognosis: A Systematic Review

Telomeres ensure genome integrity during replication. Loss of telomeric function leads to cell immortalization and accumulation of genetic alterations. The association of telomere length (TL) with breast cancer prognosis is examined through a systematic review. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2015, and relevant reviews were searched. Studies that evaluated TL (blood and/or tumor) in association with breast cancer survival or prognostic factor were included. Thirty-six studies met inclusion criteria. Overall risk of bias was critical. Eight studies reported survival outcomes. Overall, there was a trend toward an association of longer telomeres with better outcomes (tumor, not blood). Of the 33 studies reporting associations with prognostic factors, nine adjusted for potential confounders. Among the latter, shorter telomeres were associated with older age (blood, not tumor), higher local recurrence rates (normal tissue), higher tumor grade (tumor), and lower physical activity (blood), which were reported in one study each. TL was not associated with molecular subtype (blood, one study), family history (tumor, one study), chemotherapy (blood, three of four studies), and stress reduction interventions (blood, two of two studies). Although major methodologic differences preclude from drawing conclusive results, TL could be a valuable breast cancer prognostic marker. Cancer Epidemiol Biomarkers Prev; 26(1); 3–10. ©2016 AACR.
Evaluation of responses to vitamin D3 (cholecalciferol) in patients on dialysis: a systematic review and meta-analysis

Vitamin D plays a key role in mineral metabolism and its deficiency is often noted in patients on dialysis for end-stage renal disease (ESRD). We evaluated the efficacy and responses to vitamin D3 (cholecalciferol) in patients undergoing dialysis for ESRD. Randomized controlled trials or prospective studies comparing vitamin D3 supplementation to placebo in patients with ESRD on dialysis were searched from medical databases using the terms, ‘Calcitriol/Cholecalciferol, vitamin D, chronic kidney disease, hemodialysis, serum calcium, parathyroid hormones (PTH), phosphorus, 25(OH)D, and 1,25(OH)2D’. The outcomes analyzed were serum calcium, PTH, phosphorus, 25(OH)D, and 1,25(OH) 2D levels. Of the 259 records identified, 9 studies with a total of 368 patients were chosen for the current meta-analysis. The number of patients, age, and gender distribution among the groups were comparable. Results reveal a greater increase in both 25(OH)D (Pooled difference in means=0.434, 95% CI 0.174 to 0.694, p=0.001) and 1,25(OH) 2D (Pooled difference in means=0.978, 95% CI 0.615 to 1.34, p<0.001) in the treatment arm, as compared to the placebo. There was no difference in the serum calcium or PTH among the two groups. However, patients in the treatment arm had a significant increase in phosphorus levels (Pooled difference in means=0.434, 95% CI 0.174 to 0.694, p=0.001). Vitamin D supplementation facilitated the maintenance of increased levels of 25(OH) D and 1,25(OH) 2D in patients undergoing dialysis for ESRD. This increase in vitamin D was not associated with hypercalcemia or significant changes in PTH levels.
Ice–liquid isotope fractionation factors for 18O and 2H deduced from the isotopic correction constants for the triple point of water

ABSTRACT The stable isotopes of water are extensively used as tracers in many fields of research. For this use, it is essential to know the isotope fractionation factors connected to various processes, the most important of which being phase changes. Many experimental studies have been performed on phase change fractionation over the last decades. Whereas liquid–vapour fractionation measurements are relatively straightforward, vapour–solid and liquid–solid fractionation measurements are more complicated, as maintaining equilibrium conditions when a solid is involved is difficult. In this work, we determine the ice–liquid isotope fractionation factors in an indirect way, by applying the Van’t Hoff equation. This equation describes the relationship of the fractionation factors with isotope-dependent temperature changes. We apply it to the recently experimentally determined isotope dependences of the triple point temperature of water [Faghihi V, Peruzzi A, Aerts-Bijma AT, et al. Accurate experimental determination of the isotope effects on the triple point temperature of water. I. Dependence on the 2H abundance. Metrologia. 2015;52:819–826; Faghihi V, Kozicki M, Aerts-Bijma AT, et al. Accurate experimental determination of the isotope effects on the triple point temperature of water. II. Combined dependence on the 18O and 17O abundances. Metrologia. 2015;52:827–834]. This results in new values for the 2H (deuterium) and 18O fractionation factors for the liquid–solid phase change of water, which agree well with existing, direct experimental data [Lehmann M, Siegenthaler U. Equilibrium oxygen- and hydrogen-isotope fractionation between ice and water. J Glaciol. 1991;37:23–26]. For 2H, the uncertainty is improved by a factor of 3, whereas for 18O the uncertainty is similar. Our final results are αS–L (2H/1H) = 1.02093(13), and αS–L (18O/16O) = 1.002909(25), where the latter is the weighted average of the previous experimental study and this work.
Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women

Summary Women with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during Gravidity [EThIG]), 810 pregnant women were assigned to one of three management strategies according to pre-defined risk factors related to history of VTE and thrombophilic profile. Low-risk women (group I), received 50–100 IU dalteparin/ kg body weight/ day for 14 days postpartum, or earlier when additional risk factors occurred. Women at high (group II) or very high risk (group III) received dalteparin from enrolment until six weeks postpartum (50–100 IU and 100–200 IU/ kg/ day, respectively). Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95% confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III, 2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 % CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of heparin- induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomatic VTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.
Dynamics in the ultrastructure of asymmetric axospinous synapses in the frontal cortex of hibernating European ground squirrels (Spermophilus citellus)

Recent theories on the function of arousals from torpor in hibernating mammals focus on the repair of the central nervous system from damage accumulating during prolonged hypothermia. In this framework, we investigated the synaptic ultrastructure in Layer 2 of the frontal cortex from hibernating European ground squirrels (Spermophilus citellus) sacrificed at four different phases in the torpor‐arousal cycle. Using electron microscopy, we quantified synapse number and morphometric data on asymmetric axospinous synapses. Length, width, and surface area of postsynaptic densities (PSDs), and the synaptic apposition length of the analyzed synapse were measured. Five groups of animals were compared during entrance into torpor (Torpor Early, TE, n = 6), late torpor (Torpor Late, TL, n = 5), beginning of euthermic arousal episodes (Arousal Early, AE, n = 5), late in the euthermic arousal episode (Arousal Late, AL, n = 5), and during continuous euthermy in spring (EU, n = 6). The results showed that during torpor and at the beginning of arousals the PSD length and synaptic apposition length are significantly increased compared to synapses during late arousal and in spring conditions. In contrast, the width and surface area of the PSDs are decreased in torpor. At the beginning of an arousal the width of the PSD increases and gains maximum value in late arousals (AL), returning to spring (EU) values. No differences were found in total number of synapses during the torpor‐arousal cycle. The results indicate reversible changes in ultrastructure of (asymmetric axospinous) synapses in the frontal cortex, which may be critical for the maintenance of cortical neuronal networks and for protection against potential deleterious effects of prolonged hypothermic phases of hibernation. Synapse 61:343–352, 2007. © 2007 Wiley‐Liss, Inc.
Compensators: An alternative IMRT delivery technique

Seven years of experience in compensator intensity‐modulated radiotherapy (IMRT) clinical implementation are presented. An inverse planning dose optimization algorithm was used to generate intensity modulation maps, which were delivered via either the compensator or segmental multileaf collimator (MLC) IMRT techniques. The in‐house developed compensator‐IMRT technique is presented with the focus on several design issues. The dosimetry of the delivery techniques was analyzed for several clinical cases. The treatment time for both delivery techniques on Siemens accelerators was retrospectively analyzed based on the electronic treatment record in LANTIS for 95 patients. We found that the compensator technique consistently took noticeably less time for treatment of equal numbers of fields compared to the segmental technique. The typical time needed to fabricate a compensator was 13 min, 3 min of which was manual processing. More than 80% of the approximately 700 compensators evaluated had a maximum deviation of less than 5% from the calculation in intensity profile. Seventy‐two percent of the patient treatment dosimetry measurements for 340 patients have an error of no more than 5%. The pros and cons of different IMRT compensator materials are also discussed. Our experience shows that the compensator‐IMRT technique offers robustness, excellent intensity modulation resolution, high treatment delivery efficiency, simple fabrication and quality assurance (QA) procedures, and the flexibility to be used in any teletherapy unit. PACS numbers: 87.53Mr, 87.53Tf
A Three Revolute-Revolute-Spherical Wearable Fingertip Cutaneous Device for Stiffness Rendering

We present a novel three Revolute-Revolute-Spherical (3RRS) wearable fingertip device for the rendering of stiffness information. It is composed of a static upper body and a mobile end-effector. The upper body is located on the nail side of the finger, supporting three small servo motors, and the mobile end-effector is in contact with the finger pulp. The two parts are connected by three articulated legs, actuated by the motors. The end-effector can move toward the user's fingertip and rotate it to simulate contacts with arbitrarily-oriented surfaces. Moreover, a vibrotactile motor placed below the end-effector conveys vibrations to the fingertip. The proposed device weights 25 g for 35 x 50 x 48 mm dimensions. To test the effectiveness of our wearable haptic device and its level of wearability, we carried out two experiments, enrolling 30 human subjects in total. The first experiment tested the capability of our device in differentiating stiffness information, while the second one focused on evaluating its applicability in an immersive virtual reality scenario. Results showed the effectiveness of the proposed wearable solution, with a JND for stiffness of 208.5 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math> <alternatives><inline-graphic xlink:href="pacchierotti-ieq1-2755015.gif"/></alternatives></inline-formula> 17.2 N/m. Moreover, all subjects preferred the virtual interaction experience when provided with wearable cutaneous feedback, even if results also showed that subjects found our device still a bit difficult to use.
Levels of detection of hypertension in primary medical care and interventions to improve detection: a systematic review of the evidence since 2000

Objectives In England, many hypertensives are not detected by primary medical care. Higher detection is associated with lower premature mortality. We aimed to summarise recent evidence on detection and interventions to improve detection in order to inform policies to improve care. Design Data sources: systematic review of articles published since 2000. Searches of Medline and Embase were undertaken. Eligibility criteria: published in English, any study design, the setting was general practice and studies included patients aged 18 or over. Exclusion criteria: screening schemes, studies in primary care settings other than general practice, discussion or comment pieces. Participants: adult patients of primary medical care services. Synthesis: study heterogeneity precluded a statistical synthesis, and papers were described in summary tables. Results Seventeen quantitative and one qualitative studies were included. Detection rates varied by gender and ethnic group, but longitudinal studies indicated an improvement in detection over time. Patient socioeconomic factors did not influence detection, but living alone was associated with lower detection. Few health system factors were associated with detection, but in two studies higher numbers of general practitioners per 1000 population were associated with higher detection. Three studies investigated interventions to improve detection, but none showed evidence of effectiveness. Limitations The search was limited to studies published from 2000, in English. There were few studies of interventions to improve detection, and a meta-analysis was not possible. Conclusions and implications Levels of detection of hypertension by general practices may be improving, but large numbers of people with hypertension remain undetected. Improvement in detection is therefore required, but guidance for primary medical care is not provided by the few studies of interventions included in this review. Primary care teams should continue to use low-cost, practical approaches to detecting hypertension until evidence from new studies of interventions to improve detection is available.
Serum estradiol associates with blood hemoglobin in elderly men: the MrOS Sweden study.

CONTEXT Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been regarded as part of normal aging. However, the association between Hb and serum estradiol is incompletely known. OBJECTIVE To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. DESIGN, SETTING, AND PARTICIPANTS The MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median age, 75.3 y; range, 70-81 y). MAIN OUTCOME MEASURES We evaluated total estradiol in relation to Hb and adjusted for potential confounders (ie, age, body mass index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin status). RESULTS Estradiol correlated negatively with age (r = -0.14; P < .001). Hb correlated (age adjusted) positively with estradiol (r = 0.21; P < .001) and T (r = 0.10; P < .01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T. After exclusion of subjects with Hb <130 g/L and/or T < 8 nmol/L (n = 99), the correlation between Hb and T was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI, and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values (odds ratio per SD decrease in estradiol = 1.61 [95% confidence interval, 1.34-1.93]). Anemic subjects (Hb < 130 g/L) had lower mean estradiol than nonanemic subjects (67.4 vs 79.4 pmol/L; P < .001). CONCLUSIONS Estradiol correlated positively and independently with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.
Early skin-to-skin contact after cesarean section: A randomized clinical pilot study

Objective Early bonding by skin-to-skin contact (SSC) has been demonstrated to be beneficial for mothers and newborns following vaginal delivery. The aim of this study was to investigate the impact of intraoperative bonding (early SSC) after cesarean section on neonatal adaptation, maternal pain and stress response. Study design This prospective, randomized-controlled pilot study was performed at a single academic tertiary hospital (Department of Obstetrics and Gynecology, Medical University of Graz, Austria) between September 2013 and January 2014. Women were randomly assigned to intraoperative (“early”) SCC (n = 17) versus postoperative (“late”) SCC (n = 18). Main variables investigated were neonatal transition (Apgar score, arterial oxygen saturation, heart rate and temperature), maternal pain perception and both maternal and neonatal stress response by measuring the stress biomarkers salivary free cortisol and salivary alpha amylase. Results There was no evidence for differences in parameters reflecting neonatal transition or stress response between the ‘Early SSC Group’ and the ‘Late SSC Group’. Maternal salivary cortisol and alpha-amylase levels as well as maternal wellbeing and pain did not differ between the groups. However, the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’ (p = 0.004). Conclusions This study did not reveal significant risks for the newborn in terms of neonatal transition when early SSC is applied in the operating room. Maternal condition and stress marker levels did not differ either, although the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’, which may indicate a stressor sign due to intensive activation of the sympathetic-adreno-medullary-system. This needs to be further evaluated in a larger prospective randomized trial. Trial registration ClinicalTrials.gov NCT01894880
Influence of Menopausal Status on the Symptom Experience of Women Before Breast Cancer Surgery

Background Breast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery. Objective The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery. Methods A total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms. Results Of the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040). Conclusion Regardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age. Implications for Practice As part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.