Miracle-dz/UniFAR-FTUs huggingface dataset:
Benefit and timing of second transplantations in multiple myeloma: clinical findings and methodological limitations in a European Group for Blood and Marrow Transplantation registry study.

PURPOSE To use European Group for Blood and Marrow Transplantation registry data to assess the benefit and optimal timing of a double-autologous transplantation strategy for patients with myeloma. PATIENTS AND METHODS 7,452 transplantation patients described as being either in a multiple graft program ("planned") or not, were analyzed on an intention-to-treat basis. Subsequent multivariate analyses concentrated on the real occurrence of second transplantation, survival, relapse, and transplant-related mortality. RESULTS Although the transplantation rate in the planned group failed to reach 60%, the median survival from transplantation is 60 months for the planned, compared with 51 months for the remainder group. While the hazard ratio of the planned group is 0.89 (95% CI, 0.79 to 1.00; P =.05) before approximately 70 months, this "effect" is reversed after 70 months, with the hazard ratio estimated as 3.01 (95% CI, 1.07 to 8.46; P =.04). A time-dependent multivariate Cox analysis shows that, taking patients without a second transplantation as a reference group, those receiving a second transplantation in first remission (ie, before relapse) show an increased probability of transplant-related mortality, especially if the transplantation is performed more than 12 months after the first, and the reduction of the risk of relapse is less than when the transplantation is performed earlier. Performing a second transplantation after relapse does not seem to prolong survival, though a second transplantation before relapse is associated with a higher probability of mortality. CONCLUSION To improve survival of tandem autologous transplantation in multiple myeloma, the second transplantation should preferably be performed before relapse and within 6 to 12 months of the first transplantation.
Elevated expression of inhibin alpha in prostate cancer.

PURPOSE Less than 50% of men who undergo radical prostatectomy for prostate cancer are cured of disease. We evaluate tumor expression of inhibin alpha, a putative tumor suppressor, and the related protein, follistatin, to determine whether expression correlated with failure to be cured by surgery. MATERIALS AND METHODS Tissues were selected from an archival collection of 379 prostatectomy specimens from men with followup of at least 5 years after surgery. Since previous studies showed that such men with only Gleason grade 3 cancer had a greater than 95% chance of no biochemical recurrence (increase in serum prostate specific antigen), our investigation was confined to 174 men with 2% or greater grade 4/5 cancer. These men had an intermediate rate of failure, providing an opportunity to analyze the potential contribution of inhibin alpha or follistatin to progression. Intensity of immunohistochemical labeling for inhibin alpha and follistatin in each cancer was compared with that in normal glands within the same tissue section. RESULTS The majority of cases showed more intense expression of inhibin alpha in cancer than in normal glands. Those individuals whose cancers had the most elevated expression of inhibin alpha had a higher risk of recurrence, although this association was not statistically significant. Follistatin was expressed equivalently in normal and cancer cells in the majority of cases and did not correlate with recurrence. CONCLUSIONS Our finding that inhibin alpha is frequently overexpressed in high grade prostate cancer suggests that the role of inhibin alpha as a tumor suppressor needs to be reevaluated. Furthermore, assessment of inhibin alpha as a serum marker of prostate cancer, as used to diagnose ovarian cancer, may be warranted.
Characteristics of CryoSat-2 signals over multi-year and seasonal sea ice

CryoSat-2 Level 1B and Level 2 data are compared with coincident airborne laser scanner and airborne electromagnetic induction surveys conducted in the Baltic Sea in March 2011 and in the Lincoln Sea in March and April 2012. Across-track snagging caused range retrieval errors in all examined tracks. The L2 surface height profiles are very noisy due to poor retracker performance. Cryosat-2 L2 data are produced by tracking the strongest return in the Level 1B waveforms, not the first return. When a strong reflector is present off-nadir, the retracker incorrectly selects this surface as the surface location of the nadir point. The surface height profile is smoothed by tracking the first return point instead of the peak power return. Ice thickness data produced by retracking the CryoSat-2 L1B data showed good correlation with airborne electromagnetic induction measurements. CryoSat-2 and NASA Operation Ice Bridge data exhibited similar latitudinal freeboard gradients. Accurate measurements of sea ice freeboard or thickness changes can be achieved using appropriate spatial and temporal averaging.
Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency

Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD‐IgAD. IL‐2, TNF‐α, IL‐10, IL‐4 and IL‐13 plasma levels were measured both at diagnosis and after a gluten‐free diet (GFD) in 32 CD patients, in 27 CD‐IgAD patients and in 30 healthy controls. IFN‐γ levels were significantly higher in CD and CD‐IgAD than in controls, TNF‐α displayed significantly higher levels in CD‐IgAD when compared both with controls and with CD, and IL‐2 was in CD‐IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL‐4 and IL‐13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL‐10, whose production is stimulated by the TNF‐α, had significantly higher plasma levels in CD‐IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD‐IgAD patients display persistently higher pro‐inflammatory cytokine levels, suggesting a persistent state of activation of pro‐phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL‐10 may be an adjunctive evaluating criterion in the follow‐up of CD‐IgAD patients.
Development and testing of an audio-visual aid for improving infant oral health through primary caregiver education.

PURPOSE To create and test an audio-visual (AV) aid for providing anticipatory guidance on infant oral health to caregivers. METHODS A DVD-video containing evidence-based information about infant oral health care and prevention in accordance with the American Academy of Pediatric Dentistry guidelines has been developed (www.utoronto.ca/dentistry/newsresources/kids/). It contains comprehensive anticipatory guidance in the areas of pregnancy, oral development, teething, diet and nutrition, oral hygiene, fluoride use, acquisition of oral bacteria, feeding and oral habits, causes and sequelae of early childhood caries, trauma prevention, early dental visits and regular dental visits. A questionnaire was developed to test the knowledge of expectant and young mothers (n = 11) and early childhood educators (n = 16) before and after viewing the video. RESULTS A significant lack of knowledge about infant oral health was indicated by the proportion of "I don"t know" (22%) and incorrect (19%) responses to the questionnaire before the viewing. Significant improvement in knowledge (32%; range -3% to 57%; p < 0.001) was indicated by the proportion of correct responses (91%) following a single viewing of the AV aid. CONCLUSION This AV aid promises to be an effective tool in providing anticipatory guidance regarding infant oral health in high-risk populations. Unlike existing educational materials, this aid provides a comprehensive, self-directed, evidence-based approach to the promotion of infant oral health. Widespread application of this prevention protocol has the potential to result in greater awareness, increased use of dental services and reduced incidence of preventable oral disease in the target populations.
A New Computerized Impedance Plethysmograph: Accuracy in the Detection of Proximal Deep-Vein Thrombosis in Symptomatic Outpatients

Summary Because of the lack of specificity of the clinical diagnosis it is appropriate in patients with clinically suspected deep-vein thrombosis to apply an objective test before starting anticoagulant treatment. Impedance plethysmography is a highly accurate technique for the detection of proximal-vein thrombosis with a reported sensitivity and specificity of 93 and 97%, respectively. In all previous reported evaluations of impedance plethysmography an apparatus which was developed in 1971 was used. A new computerized impedance plethysmograph, using a novel device to measure impedance, was blindly compared against venography in 443 consecutive outpatients with clinically suspected deep-vein thrombosis. In the first phase of the study the computerized impedance plethysmography test results of 242 symptomatic patients were used to develop a discriminant line. Subsequently, this discriminant line was validated in the second phase of the study in another 201 symptomatic patients. The combined sensitivity and specificity of these two phases for proximal-vein thrombosis was 91% [95% confidence interval (Cl), 86 to 94%] and 94% (95% CI, 90 to 96%), respectively, which compares favourably with impedance plethysmography. It is concluded that computerized impedance plethysmography is a simple, portable, non-invasive technique with a high accuracy for the detection of proximal vein thrombosis. However, before computerized impedance plethysmography can be used as the only test in the diagnosis of deep-vein thrombosis, the safety of withholding anticoagulant treatment to patients with repeated normal computerized test results should be assessed during longterm follow-up studies.
The use of remote sensing in the identification of the eco–environmental factors associated with the risk of human visceral leishmaniasis (kala-azar) on the Gangetic plain, in north–eastern India

Abstract Human visceral leishmaniasis (VL) or kala-azar remains a major cause of mortality, particularly in the developing world. The disease is common in the internal regions of north–eastern India, which have a tropical or sub-tropical climate. In a recent study on VL in this region, the relationship between the incidence of VL and certain physio–environmental factors was explored, using a combination of a geographical information system (GIS), satellite imagery and data collected 'on the ground'. Some eco–environmental parameters were then used to map and describe the spatial heterogeneity seen in the transmission of the parasite (Leishmania donovani) that causes VL in India, and to identify those habitats, on the Gangetic plain, where the sandfly vectors might thrive. It was found that the presence of waterbodies, woodland and urban, built-up areas, soil of the fluvisol type, air temperatures of 25.0–27.5°C, relative humidities of 66%–75%, and an annual rainfall of 100–<160 cm were all positively associated with the incidence of VL. A VL map was created and stratified into areas of 'risk' and 'non-risk' for the disease, based on calculations of risk indices.
The activated transforming growth factor‐beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer

Peritoneal dissemination including omental metastasis is the most frequent route of metastasis and an important prognostic factor in advanced ovarian cancer. We analyzed the publicly available microarray dataset (GSE2109) using binary regression and found that the transforming growth factor (TGF)‐beta signaling pathway was activated in omental metastases as compared to primary sites of disease. Immunohistochemical analysis of TGF‐beta receptor type 2 and phosphorylated SMAD2 indicated that both were upregulated in omental metastases as compared to primary disease sites. Treatment of the mouse ovarian cancer cell line HM‐1 with recombinant TGF‐β1 promoted invasiveness, cell motility and cell attachment while these were suppressed by treatment with A‐83‐01, an inhibitor of the TGF‐β signaling pathway. Microarray analysis of HM‐1 cells treated with TGF‐β1 and/or A‐83‐01 revealed that A‐83‐01 efficiently inhibited transcriptional changes that are induced by TGF‐β1. Using gene set enrichment analysis, we found that genes upregulated by TGF‐β1 in HM‐1 cells were also significantly upregulated in omental metastases compared to primary sites in the human ovarian cancer dataset, GSE2109 (false discovery rate (FDR) q = 0.086). Therapeutic effects of A‐83‐01 in a mouse model of peritoneal dissemination were examined. Intraperitoneal injection of A‐83‐01 (150 μg given three times weekly) significantly improved survival (p = 0.015). In summary, these results show that the activated TGF‐β signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.
Involvement of granzyme B and perforin in suppressing nodal metastasis of cancer cells in breast and lung cancers.

AIMS Granzyme B and perforin, which are contained in cytotoxic granules produced by tumour-infiltrating immune cells, have been reported to be involved in suppression of cancer progression. In this study, the relationship between expression of these molecules and clinical factors in cancer patients was studied. METHODS Tumour tissue obtained from 23 breast cancer patients and 13 lung cancer patients were examined for expression of granzyme B, perforin and B7-1, using an immunohistochemical technique. The percentage of cells positive for expression of these molecules and the clinical status of each case were compared. RESULTS Both granzyme B and perforin were distributed in the cytoplasm of cancer cells in many cases rather than in tumour-infiltrating lymphocytes. This was observed even in cases of early-stage tumours. In both breast and lung cancer patients, the percentage of cells positive for granzyme B and perforin expression was inversely correlated with the status of regional node metastasis. A competitive RT-PCR analysis confirmed that the expression of mRNA from these molecules extracted from the tumours was consistent with the immunohistochemical results. CONCLUSION Granzyme B and perforin may play a role in the suppression of nodal metastasis of cancer cells in breast and lung cancers.
Value of Cardiovascular Magnetic Resonance Imaging in Noninvasive Risk Stratification in Tetralogy of Fallot

Importance Adults late after total correction of tetralogy of Fallot (TOF) are at risk for major complications. Cardiovascular magnetic resonance (CMR) imaging is recommended to quantify right ventricular (RV) and left ventricular (LV) function. However, a commonly used risk model by Khairy et al requires invasive investigations and lacks CMR imaging to identify high-risk patients. Objective To implement CMR imaging in noninvasive risk stratification to predict major adverse clinical outcomes. Design, Setting, and Participants This multicenter study included 575 adult patients with TOF (4.083 patient-years at risk) from a prospective nationwide registry in whom CMR was performed. This study involved 5 tertiary referral centers with a specialized adult congenital heart disease unit. Multivariable Cox hazards regression analysis was performed to determine factors associated with the primary end point. The CMR variables were combined with the noninvasive components of the Khairy et al risk model, and the C statistic of the final noninvasive risk model was determined using bootstrap sampling. The data analysis was conducted from January to December 2016. Main Outcomes and Measures The composite primary outcome was defined as all-cause mortality or ventricular arrhythmia, defined as aborted cardiac arrest or documented ventricular fibrillation and ventricular tachycardia (lasting ≥30 seconds or recurrent symptomatic). Results Of the 575 patients with TOF, 57% were male, and the mean (SD) age was 31 (11) years. During a mean (SD) follow-up of 7.1 (3.5) years, the primary composite end point occurred in 35 patients, including all-cause mortality in 13 patients. Mean (SD) RV ejection fraction (EF) was 44% (10%), and mean (SD) LV EF was 53% (8%). There was a correlation between RV EF and LV EF (R, 0.36; 95% CI, 0.29-0.44; P < .001). Optimal thresholds for ventricular function (RV EF <30%: hazard ratio, 3.90; 95% CI, 1.84-8.26; P < .001 and LV EF <45%: hazard ratio, 3.23; 95% CI, 1.57-6.65; P = .001) were independently predictive in multivariable analysis. Both thresholds were included in a point-based noninvasive risk model (C statistic, 0.75; 95% CI, 0.63-0.85) and combined with the noninvasive components of the Khairy et al risk model. Conclusions and Relevance In patients with repaired TOF, biventricular dysfunction on CMR imaging was associated with major adverse clinical outcomes. The quantified thresholds (RV EF <30% and LV EF <45%) may be implemented in noninvasive risk stratification.
An intrinsic progenitor defect in Diamond‐Blackfan anaemia

Summary. To determine whether the erythropoietin (epo) insensitivity of erythroid progenitor differentiation in congenital pure red cell aplasia or Diamond‐Blackfan anaemia is intrinsic to the progenitor itself or is due to defective accessory cell function or active suppression, progenitors from normals and two patients (one steroid resistant and one spontaneously remitting), separated from all known accessory cells using sequential negative selection techniques (adherence, E‐rosetting, and direct and indirect immune‐panning), were studied. Initially, we evaluated three patients with DBA using unfractionated bone marrow mononuclear cells. Progenitors from two steroid non‐responsive patients showed insensitivity to crude epo (c‐epo) while one steroid responsive patient demonstrated normal in vitro sensitivity to c‐epo. When recombinant epo (r‐epo) was used in place of c‐epo, the two steroid non‐responders continued to demonstrate in vitro progenitor epo insensitivity. However, sensitivity of progenitors from the steroid responder, which was normal in the presence of c‐epo, became abnormal when recombinant epo (r‐epo) was substituted. Thus, using unfractionated bone marrow, the abnormal response to epo of progenitors from some patients with DBA appears to be obscured by stimulating factors termed erythroid burst‐promoting activity (BPA) which are present in c‐epo. Using fractionated highly enriched progenitors, from normals and a steroid responsive patient a final 3–10‐fold enrichment of progenitors was achieved, but no such enrichment was seen when marrow from a steroid resistant patient was cultured. The epo sensitivities of normal and of patient erythroid progenitors were similar. However, at sub‐optimal epo concentrations in both patients CFU‐E responsiveness to crude BPA was abnormal compared to the three controls. We conclude from these studies that in DBA: (a) the failure of erythropoiesis is due to an intrinsic progenitor defect; (b) this defect involves progenitor insensitivity to factors in addition to erythropoietin; and (c) there exists a spectrum of disease reflected in the degree of the in vitro abnormality observed.
Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma1

The active metabolite of vitamin D (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)) is known to modulate the immune response in Th1 cell-directed diseases. To investigate the role of vitamin D in Th2 cell-directed diseases, experimental allergic asthma was induced in vitamin D receptor (VDR) knockout and in wild-type (WT) mice. As expected, WT mice developed symptoms of airway inflammation with an influx of eosinophils, elevated Th2 cytokine levels, mucous production, and airway hyperresponsiveness. The administration of 1,25(OH)2D3 had no effect on asthma severity. The only discernable effect of 1,25(OH)2D3 on experimental allergic asthma in WT mice was an increased expression of two Th2-related genes (soluble CD23 and GATA-3) in lungs of BALB/c mice exposed to Ag through the nasal route only. By contrast, asthma-induced VDR knockout mice failed to develop airway inflammation, eosinophilia, or airway hyperresponsiveness, despite high IgE concentrations and elevated Th2 cytokines. The data suggest that although 1,25(OH)2D3 induced these Th2-type genes, the treatment failed to have any affect on experimental asthma severity. However, VDR-deficient mice failed to develop experimental allergic asthma, suggesting an important role for the vitamin D endocrine system in the generation of Th2-driven inflammation in the lung.
Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension.

OBJECTIVE To assess the prognostic significance of left ventricular mass and geometry in initially healthy persons with essential hypertension. DESIGN An observational study of a prospectively identified cohort. SETTING University medical center. PATIENTS Two hundred and eighty patients with essential hypertension and no pre-existing cardiac disease were evaluated using echocardiography between 1976 and 1981. Two hundred and fifty-three subjects or their family members (90%) were contacted for a follow-up interview an average of 10.2 years after the initial echocardiogram was obtained; the survival status of 27 patients lost to follow-up was ascertained using National Death Index data. MEASUREMENTS AND MAIN RESULTS Left ventricular mass exceeded 125 g/m2 in 69 of 253 patients (27%). Cardiovascular events occurred in a higher proportion of patients with than without left ventricular hypertrophy (26% compared with 12%; P = 0.006). Patients with increased ventricular mass were also at higher risk for cardiovascular death (14% compared with 0.5%; P less than 0.001) and all-cause mortality (16% compared with 2%; P = 0.001). Electrocardiographic left ventricular hypertrophy did not predict risk. Patients with normal left ventricular geometry had the fewest adverse outcomes (no cardiac deaths; morbid events in 11%), and those with concentric hypertrophy had the most (death in 21%; morbid events in 31%). In a multivariate analysis, only age and left ventricular mass--but not gender, blood pressure, or serum cholesterol level--independently predicted all three outcome measures. CONCLUSIONS Echocardiographically determined left ventricular mass and geometry stratify risk in patients with essential hypertension independently of and more strongly than blood pressure or other potentially reversible risk factors and may help to stratify the need for intensive treatment.