Miracle-dz/UniFAR-FTUs huggingface dataset:
Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group

Background Despite the favorable results of imatinib front line in chronic-phase chronic myeloid leukemia there is room for improvement. Design and Methods Early intervention during imatinib therapy was undertaken in 210 adults with chronic-phase chronic myeloid leukemia less than three months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At three months, dose was increased if complete hematologic response was not achieved. At six months, patients in complete cytogenetic response were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa. At 18 months, randomized patients were switched to a 2nd generation tyrosine kinase inhibitor if not in complete cytogenetic response and imatinib dose increased in non-randomized patients not in major molecular response. Results Seventy-two percent of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2–78) months. At three months 4 patients did not have complete hematologic response; at six months 73.8% were in complete cytogenetic response; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned to high imatinib dose, and 15 to 400 mg + interferon-alpha. The low number of randomized patients precluded comparison between the two arms. Cumulative response at three years was: complete hematologic response 98.6%, complete cytogenetic response 90% and major molecular response 82%. On an intention-to-treat basis, complete cytogenetic response was 78.8% at 18 months. At five years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure free survival 82.5%, and event free survival (including permanent imatinib discontinuation) 71.5%. Conclusions These results indicate the benefit of early intervention during imatinib therapy (ClinicalTrials.gov Identifier: NCT00390897).
Refractory thrombotic thrombocytopenic purpura in a 16‐year‐old girl: successful treatment with bortezomib

We present a case of a 16‐year‐old girl with autoimmune thrombotic thrombocytopenic purpura (TTP), refractory to plasma exchange and high‐dose prednisone. Despite the additional treatment with rituximab, she developed renal and neurological complications with ongoing hemolysis and thrombocytopenia. Bortezomib, a proteasome inhibitor and thereby blocking plasma cells, was added, and our patient recovered. We suggest that bortezomib can be of additional value in severe immunologically mediated TTP in adolescents. Its use may prevent the necessity of other invasive therapies, such as splenectomy, with significant side effects.
Low complication rates in the use of port-a-caths in oncology patients.

BACKGROUND Port-a-caths (PACs) represent an important component of the care of cancer patients, in particular for administration of chemotherapy. We sought to analyse the longevity and complications of PACs in cancer patients in a large community hospital. METHODS We retrospectively analysed the indications, duration of use, complications and reasons for removal of PACs in cancer patients treated in our centre from January 2005 to December 2010, and compared these with findings in patients who received a PAC in the same period for reasons not related to cancer. RESULTS During the study period 152 cancer patients received a total of 170 PACs; in the same period, 21 patients received a total of 35 PACs for reasons unrelated to cancer. The total analysis comprised 70,919 days of PAC use. Most cancer patients had a solid tumour (97%). PACs were removed because of a complication in 25 cases in cancer patients (14.7%) vs 15 cases in non-cancer patients (42.9%, p.
Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism

Summary The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012–6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19% (95%CI=10–27%) reduction in recurrent VTE and a 21% (95%CI=4–35%) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients’ hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies. Supplementary Material to this article is available at www.thrombosis-online.com.
Influences of Mechanical Stress on Prenatal and Postnatal Skeletal Development

A new theory is introduced to describe some of the influences of mechanical stresses on chondroosseoubiology. It is proposed that degeneration and ossification is a normal process for all cartilage in the appendicular skeleton, which is (1) accelerated by intermittently applied shear stresses (or strain energy), and (2) inhibited or prevented by intermittently applied hydrostatic pressure. These concepts were applied using finite element computer models in an effort to predict the ossification pattern of the prenatal and postnatal femoral anlage. The theoretical calculations successfully predicted the key features of skeletal morphogenesis including the development of (1) the primary ossification site, (2) a tubular diaphysis and marrow cavity, (3) meta-phys-al and epiphyseal trabecular bone, (4) the location and geometry of the growth plate, (5) the appearance and location of the secondary ossific nucleus, and (6) the existence and thickness distribution of articular cartilage. The results suggest that degenerative joint disease in immobilized or non-load-bearing mature joints may be a manifestation of the final stage in the ossification of the anlage. In nonfunctional joints, the absence or reduction of intermittent hydrostatic pressure in the articular cartilage permits cartilage degeneration and the progressive advance of the ossification front toward the joint surface until the articular cartilage has been ossified.
Cyclooxygenase-2 Expression in Inflammatory Lung Lesions of Nonhuman Primates

Mammalian cells contain two related but unique isoforms of cyclooxygenase (COX-1 and COX-2). COX-1 is expressed constitutively in a majority of tissues and is involved in the production of prostaglandins (PGs) that modulate normal physiologic functions. COX-2 is inducible by various stimuli and is involved in the production of PGs that modulate physiologic events in development, cell growth, and inflammation. With the exception of peribronchial glands and chondrocytes of peribronchial cartilage, COX-2 is not detectable in the normal lung of nonhuman primates. We evaluated COX-2 expression by immunohistochemical methods in the inflammatory lesions of two cynomolgus monkeys (Macaca fascicularis) with acute severe pneumonia. Both monkeys exhibited acute severe bronchopneumonia; histologically, lung lesions were characterized by infiltration of large numbers of neutrophils and fewer macrophages, mild bronchial epithelial hyperplasia, and slight type-2 pneumocyte hyperplasia. In both monkeys, mild to marked COX-2 immunoreactivity was detected within the cytoplasm of macrophages, bronchial epithelial cells, type-2 pneumocytes, and endothelial cells of blood vessels. No COX-2 immunoreactivity was detectable in the neutrophils that constituted >90% of the inflammatory cells. These observations suggest that in acute inflammatory lung lesions in nonhuman primates 1) COX-2 is induced in the bronchial and alveolar epithelial cells, 2) macrophages are the primary inflammatory cells that exhibit COX-2, and 3) neutrophils do not express COX-2.
Endorsement of Interpersonal Strategies for Dealing with Hypothetical Everyday Arthritis Problems as a Function of Marital Status, Gender, and Problem Severity

We used hypothetical vignettes to examine whether older adults' endorsement of interpersonal strategies for dealing with health-related (arthritis) everyday problems varied as a function of marital status, gender, and the severity of the problem. Adults 60 years and older (N = 127, M = 71.40 years, SD = 7.21) rated interpersonal (i.e., discuss with doctor, spouse, relative) and other strategies (e.g., deal with the problem alone, pray) for solving two hypothetical everyday problems (one mild and one severe arthritis problem). Women reported a greater likelihood of using interpersonal strategies. Married people rated interpersonal strategies that involved their spouse higher than other strategies. Greater severity of problems was associated with greater endorsement of interpersonal strategies. Implications of the results for understanding the conditions under which older adults endorse strategies that may initiate collaborative everyday problem solving are discussed.
On building causal networks for Chinese stock market understanding

This study proposes a causal network construction method based on Granger causality test rather than correlation coefficient to investigate the inherent structure of the stock market. We analyze the characteristics, community structure and nodes' influence of the network formed following our method. Furthermore, this study investigates the reasons why the stock market performs a certain relationship among stocks and why some stocks can be important in the stock market. This is the first paper tries to illustrate the mechanism of stock network. This paper proposes a new way to analyze the formation reasons of community structure and important nodes of the stock market, which integrates complex networks and financial econometric methods. This paper conducts empirical study for Chinese stock market to illustrate the usefulness and advantage of our new methods. The empirical results show that it is the pricing factors such as yearly abnormal returns, price volatility, price level and leverage that drives the stocks rather than industry sector. Our study provides new evidence to help us understand the stock market and stock pricing. Particularly, the results of this paper can help understand the sector rotation effect in the stock market.
Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction*

Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the adult heart. The heart can utilize unesterified FA bound to albumin or FA obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two sources of FA are interchangeable and necessary for optimal heart function. Hearts unable to obtain FA from lipoprotein TG were able to compensate by increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had decreased expression of pyruvate dehydrogenase kinase 4 and increased cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction expression levels of genes regulating FA and glucose metabolism were acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48 h of abdominal aortic constriction. Older hLpL0 mice developed cardiac dysfunction characterized by decreased fractional shortening and interstitial and perivascular fibrosis. HLpL0 hearts had increased expression of several genes associated with transforming growth factor-β signaling. Thus, long term reduction of lipoprotein FA uptake is associated with impaired cardiac function despite a compensatory increase in glucose utilization.
Endoscopic ultrasound in the follow up and response assessment of patients with primary gastric lymphoma

Background: Endoscopic ultrasound (EUS) is considered the best technique for local staging of primary gastric lymphomas. Its role in the follow up of patients with gastric lymphoma following organ conserving strategies has not been established. Aim: To compare endosonographic response assessment with results of histological evaluation. Patients and methods: Thirty three patients with primary gastric lymphomas underwent pretreatment EUS and were followed endosonographically every 3–6 months after administration of organ conserving treatment modalities. A wall thickness of ≤4 mm with preserved five layer structure and the absence of suspicious lymph nodes was defined as endosonographic remission. Decrease in wall thickness, increase in echogenicity, and regression of lymph nodes were tested for their value to predict histological remission. Results: A total of 158 endosonographies were performed (median 4; range 2–12). Within a median follow up period of 15 months (range 3–48), 27 (82%) patients achieved complete histological remission while endosonographic remission was found in 21 (64%) patients. Eighteen patients achieved both forms of remission, with endosonographic remission occurring later (35.1 (11–212.9) weeks v 17.6 (11–97.9) weeks; median (range); p<0.02) than histological remission. A further three patients demonstrated a false negative remission on EUS. Histological relapse was paralleled by endosonographic relapse in only one of five patients. None of the tested endosonographic parameters was able to predict histological remission. Conclusions: In view of the inferior accuracy of EUS when compared with histology, gastroscopy with biopsy seems sufficient for the routine follow up of patients with gastric lymphoma.
How Do Turkish Middle School Science Coursebooks Present the Science Process Skills

used for teaching science at the 5th to 8th grade were analyzed. The findings show that activities in the coursebooks are in the planning and starting skill level of SPS. The overall investigation of the science coursebooks revealed that the SPS recommended in science curriculums are not reflected in the science coursebooks used in middle schools. Skills like variables determination and controlling-changing variables are either included at the lowest rates or not at all in the science coursebooks employed. In addition, the representation of each skill varies according to the grade, publisher, and unit.
Basal variability in CREB phosphorylation predicts trait-like differences in amygdala-dependent memory

Significance Most studies in neuroscience focus on average, or typical, behavior; however, much less is known about how neurobiological differences between individuals contribute to their cognitive and emotional characteristics. In this study, we use outbred rats to investigate if CREB, a key protein required for memory formation, participates in the natural emergence of memory-related individual differences. We show that CREB is activated at lower levels in rats with trait-like deficits in emotional memory. Thus, even in genetically diverse populations, naturally occurring differences in the function of specific proteins may contribute to defining common behavioral traits. Much of what is known about the neurobiology of learning and memory comes from studies of the average behavior. In contrast, intersubject differences that emerge within groups are difficult to study systematically and are often excluded from scientific discussion. Nevertheless, population-wide variability is a virtually universal feature of both complex traits, such as intelligence, and hardwired responses, such as defensive behaviors. Here, we use outbred rats to investigate if cAMP response element-binding protein (CREB), a transcription factor that has long been known in experimental settings to be crucial for associative plasticity, participates in natural memory phenotypes. Using a combination of behavioral, biochemical, and viral techniques, we show that a subset of rats with trait-like deficits in aversive memory have basally reduced CREB activity in the lateral amygdala but can be induced to perform at average levels by directly or indirectly enhancing pretraining CREB phosphorylation. These data suggest that endogenous CREB activity in the amygdala may set a critical threshold for plasticity during memory formation.
A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.
Wound healing in partial-thickness burn wounds treated with collagenase ointment versus silver sulfadiazine cream.

During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization. Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation, the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing. Collagenase digests native and denatured collagen in necrotic tissue. This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of standard topical antimicrobial therapy (control) in which silver sulfadiazine cream (1%) was used to debride paired burn sites. Patients selected for the study had two noncontiguous, partial-thickness, comparably sized, and anatomically similar burn wounds. Ages of patients ranged from 5 to 60 years (mean 33 years). The total body surface area burned ranged from 2% to 30% (mean 13.6%). Mean burn sizes used for study treatment were 366 cm2 (26 to 2310 cm2) for collagenase sites and 355 cm2 (26 to 2394 cm2) for control sites. Sites on each patient were randomly assigned to treatment with either collagenase or control. Endpoints were time to clean wound bed (absence of retained debris) and time to healing (complete epithelialization). The sites treated with collagenase cleaned in less time (mean 9.3 days) than the control sites (mean 11.6 days). Similarly the collagenase sites healed faster than the control sites (mean 19 vs 22.1 days). (ABSTRACT TRUNCATED AT 250 WORDS)
Predicting adolescent mental health service use in a prospective record-linkage study.

OBJECTIVE To test to what extent demographic variables and parent-reported problems and competencies in early adolescence predict incidence of mental health service use across a 5-year period in the general population. METHOD Data on parent-reported problem behavior (Child Behavior Checklist [CBCL]), gathered on 2,496 Dutch young adolescents, aged 10 to 12 years in 1989-1990, were linked to psychiatric case register data over the years 1990-1994. Cox proportional hazards models were used to predict the incidence of using mental health services from problem behavior, competencies, and demographic covariates. RESULTS Almost all CBCL problem scales predicted the incidence of mental health service use significantly. The effect was constant over time for most scales, but it decreased over time for others. CBCL Activities, gender, and one-parent family were significant predictors after accounting for the problem levels. All effects were similar for boys and girls. CONCLUSIONS In many cases, there is a remarkable delay between the awareness of the adolescent's problems and seeking and/or receiving professional help. Longitudinal studies that use continuous information on service use yield a more comprehensive picture of the utilization of mental health services than studies that aggregate the information over the follow-up period.
Excellence Through Evidence: Securing Collegial/Collaborative Nurse-Physician Relationships, Part 2

Multiple nurse-physician (RNMD) relationships coexist on hospital units; collegial and collaborative (C/C) relationships positively impact patient outcomes more than the others. The goal of this multisite evidence-based management practice initiative was to identify structures that enable C/C RNMD relationships. In part 1, the authors discussed the methodology of the study, presented the results of the literature analysis, and the description and characteristics of the clinical units, experts interviewed, and of the collegial and collaborative RNMD relationships found in the 5 participating hospitals. Part 2 analyzes the extent to which the 5 structures identified by the National Joint Practice Commission as necessary for RNMD collaboration are present in the 5 hospitals, the structures identified by the experts in this study, and suggestions and implications for management practice.