Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental and contextual influences on autonomic reactivity in young children.

Studies of cardiovascular reactivity in young children have generally employed integrated, physiologically complex measures, such as heart rate and blood pressure, which are subject to the multiple influences of factors such as blood volume, hematologic status, thermoregulation, and autonomic nervous system (ANS) tone. Reactivity studies in children have rarely employed more differentiated, proximal measures of autonomic function capable of discerning the independent effects of sympathetic and parasympathetic responses. We describe 1) the development, validity, and reliability of a psychobiology protocol assessing autonomic reactivity to challenge in 3- to 8-year-old children; 2) the influences of age, gender, and study context on autonomic measures; and 3) the distributions of reactivity measures in a normative sample of children and the prevalences of discrete autonomic profiles. Preejection period (PEP) and respiratory sinus arrythmia (RSA) were measured as indices of sympathetic and parasympathetic nervous system reactivity, respectively, and autonomic profiles were created to offer summative indices of PEP and RSA response. Results confirmed the protocol's validity and reliability, and showed differences in autonomic reactivity by age and study context, but not by gender. The studies' findings offer guidelines for future research on autonomic reactivity in middle childhood and support the feasibility of examining sympathetic and parasympathetic responses to challenge in 3- to 8-year-old children.
Qualitative-fuzzy system identification of complex dynamical systems

Fuzzy systems have been proved to be excellent candidates for system dynamics identification. However, they are affected by two drawbacks: the resulting nonlinear model (i) does not guarantee that the generalization property holds unless a large amount of samples is employed, and (ii) is not understandable from a physical viewpoint. These drawbacks are particularly serious when fuzzy identification deals with complex natural systems as the observational data set and/or empirical knowledge can occur to be inadequate. For these systems, the available knowledge of the underlying mechanisms is qualitative and highly incomplete, and does often prevent from formulating a quantitative differential model but not a qualitative one. This paper demonstrates that Qualitative Reasoning methods properly integrated with fuzzy systems yield a hybrid system identification method that overcomes the problems outlined above.
New evidence guiding extent of lymphadenectomy for esophagogastric junction tumor: Application of Ber-Ep4 Joint with CD44v6 staining on the detection of lower mediastinal lymph node micrometastasis and survival analysis

Abstract For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively. A total of 1325 lymph nodes were collected from 49 patients, grouped into 3 groups: lower mediastinal, paracardial, and abdominal. The former 2 groups were examined by monoclonal antibodies against Ber-Ep4 and CD44v6. The incidence of LNMM in mediastinal group was 37% (18/49) for Ber-Ep4 and 33% (16/49) for CD44v6. While in routine histological diagnosis, the number of patients with the positive lymph nodes was 7 (14%). When combining IHC with histopathology (HE) staining, the incidence of positive mediastinal lymph nodes was increased to 24%, with a total number of 37 lymph nodes from 28 patients (57%). Micrometastases indicated by Ber-Ep4 and CD44v6 were associated with the depth of tumor invasion (P = 0.020 and 0.037, respectively), histopathological nodal status (P = 0.024 and 0.01, respectively), and Lauren classification (P = 0.038 and, respectively). Expression of CD44v6 and Ber-Ep4 was positively correlated (r = 0.643, P < 0.001). The 3- and 5-year survival rates for all patients were 66% and 50%, respectively. The patients with LNMM had a lower 3-year survival rate of 51%, compared to 80% from no LNMM group; 5-year survival rate was also lower in LNMM group, which is 29% versus 68% (P = 0.006) in the no LNMM group. Patients with positive Ber-Ep4 cells had a lower survival, but not statistically significant (P = 0.058). CD44v6-positive group had a significantly reduced survival (P < 0.001). In patients group with negative lower mediastinal lymph nodes, patients without LNMM obtained a significant survival benefit (P = 0.021). Our study demonstrated that routine test for LNMM is necessary for patients with negative lymph nodes. As a positive prognostic factor, thorough lower mediastinal lymphadenectomy in an invasive approach should be considered when necessary. Ber-Ep4 and CD44v6 were shown to be great markers for detecting LNMM.
Intraductal carcinoma of the prostate: Precursor or aggressive phenotype of prostate cancer?

Although the term “intraductal carcinoma of the prostate” (IDC‐P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN).
Previous infection and the risk of ischaemic stroke in Italy: the IN2 study

There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population.
Diabetes Mellitus tipo 2: Aspectos fisiológicos, genéticos e formas de exercício físico para seu controle

Resumo – Diabetes Mellitus tipo 2 (DM2) e uma doenca metabolica caracterizada por hiperglicemia e disfuncoes cardiovasculares, as quais podem ser controladas com exercicios fisicos, controle dietetico e tratamento farmacologico. Pesquisas recentes tem demonstrado associacoes entre DM2 e alguns polimorfismos geneticos, em especial do gene da Enzima Conversora de Angiotensina (ECA). A proposta desse estudo foi abordar a fisiopatologia do DM2 e a pratica de exercicio fisico como forma de controle nao farmacologico da glicemia e pressao arterial destes pacientes, bem como a associacao entre o DM2 e polimorfismos do gene da ECA. A pesquisa incluiu livros da area de saude, bem como artigos de revisao e originais referentes ao tema abordado, pesquisados nos bancos de dados disponiveis na internet: Pubmed, Scielo e Portal Capes. As palavras chave utilizadas foram “blood glucose”, “type 2 diabetes”, “exercise”, “blood pressure” e “ACE gene polymorphism”, e suas traducoes para a lingua portuguesa. Os principais assuntos do presente artigo referem-se a pratica diaria de exercicios, tipo e intensidades adequadas que tem se mostrado eficazes no controle glicemico e hemodinâmico, assim como as possiveis relacoes com os polimorfismos da ECA, que ainda se apresentam incipientes, pois a constatacao de associacoes entre estes podem ser fortemente influenciadas pelo tipo de populacao estudada. Os beneficios do exercicio sao indiscutiveis e suas recomendacoes apresentadas nesta revisao. Porem a literatura ainda e carente de estudos analisando os efeitos do exercicio fisico para diabeticos, considerando sua relacao com aspectos geneticos, o que coloca este assunto em evidencia como objeto de estudo na atualidade. Palavras-chave: Diabetes Mellitus; Exercicio fisico; Polimorfismo genetico.
Conversion From Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients: 24-Month Efficacy and Safety Results From the CONVERT Trial

Background. The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. Methods. Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20–40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. Results. Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. Conclusions. At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.
Optimization of frequency tunable matching circuits

As more and more wireless bands are introduced it is increasingly difficult to cover all those bands using a passive antenna system. For example, for LTE wireless devices there is growing interest in using tunable matching circuits to adapt the antenna operation to all the required operation bands. The tunable elements may be used in the matching circuit or placed within the antenna volume or a special tuning port. In the optimization of frequency tunable matching circuits it is important to maximize the efficiency of power transfer instead of maximizing just the impedance match. It is shown that the optimization of tunable matching circuits can be viewed as a two-level optimization procedure, where both the values of fixed matching components and the values of tunable matching components for each frequency band are optimized simultaneously.
Excitable behavior in amoeboid chemotaxis

Chemotaxis, the directed motion of cells in response to chemical gradients, is a fundamental process. Eukaryotic cells detect spatial differences in chemoattractant receptor occupancy with high precision and use these differences to bias the location of actin‐rich protrusions to guide their movement. Research into chemotaxis has benefitted greatly from a systems biology approach that combines novel experimental and computational tools to pose and test hypotheses. Recently, one such hypothesis has been postulated proposing that chemotaxis in eukaryotic cells is mediated by locally biasing the activity of an underlying excitable system. The excitable system hypothesis can account for a number of cellular behaviors related to chemotaxis, including the stochastic nature of the movement of unstimulated cells, the directional bias imposed by chemoattractant gradients, and the observed spatial and temporal distribution of signaling and cytoskeleton proteins. WIREs Syst Biol Med 2013, 5:631–642. doi: 10.1002/wsbm.1230
HA22 (R490A) Is a Recombinant Immunotoxin with Increased Antitumor Activity without an Increase in Animal Toxicity

Purpose: RFB4 (dsFv)-PE38 (BL22) is a recombinant immunotoxin containing an anti-CD22 (Fv) fused to truncated Pseudomonas exotoxin A, which induces a high complete remission rate in patients with purine analogue–resistant hairy cell leukemia. HA22 is a mutant of BL22 with mutations in heavy-chain CDR3 resulting in increased cytotoxic activity. Our goal was to improve the activity of HA22. Experimental Design: Arg490, which is located in the catalytic domain (III) of the immunotoxin HA22, was mutated to alanine. Purified immunotoxins were produced and tested for cytotoxic activity in cell culture and for antitumor activity and nonspecific toxicity in mice. ADP-ribosylation activity was also measured. Results: HA22 (R490A) is ∼2-fold more cytotoxic than HA22 on several CD22-positive cell lines. When injected i.v. , HA22 (R490A) has more potent antitumor activity than HA22 against CA46 tumors in mice. HA22 and HA22 (R490A) have similar LD50s (∼1.3 mg/kg) and similar plasma half-lives. The R490A mutation also improved the cytotoxicity of the antimesothelin recombinant immunotoxin SS1 (dsFv)-PE38 (SS1P). In vitro ADP-ribosylation assays show that HA22 R490A has increased activity. Increased cytotoxic activity is probably related to this increase in ADP-ribosylation activity. Conclusion: Protein engineering can be used to increase the efficacy of recombinant immunotoxins. Because HA22 (R490A) has increased antitumor activity without increased animal toxicity, immunotoxins with this mutation are candidates for clinical development.
Pro-opiomelanocortin in human pregnancy: evolution of maternal plasma levels, concentrations in cord blood, amniotic fluid and at the feto-maternal interface.

OBJECTIVE The human placenta normally expresses the pro-opiomelanocortin (POMC) gene. The pattern and secretory kinetics of POMC and/or POMC-derived peptides by the placenta during gestation is still debated. We recently demonstrated that full length POMC was a normal product of the human placenta. The aim of our study was to establish its normal secretory kinetics and to explore its physiological relevance. DESIGN In a prospective, longitudinal study, thirty normal pregnant women had monthly measurements of plasma POMC. In a cross-sectional study of 128 healthy pregnant women, plasma POMC and human chorionic gonadotrophin (hCG) were concomitantly measured to assess their correlation. Finally, POMC levels were assessed in venous and arterial cord blood samples, in amniotic fluid and in retroplacental blood. METHODS Plasma POMC was measured by a specific IRMA in unextracted blood or biological fluid. RESULTS Plasma POMC became detectable by the 8th week of pregnancy and reached its maximum at around the 20th week, remaining stable thereafter. The relationship between POMC and gestation time (weeks) best fitted with a third degree polynomia curve. A significant negative correlation (P=0.01) was observed between plasma levels of POMC and hCG after adjustment for gestation time to take into account the dependence of both hormones on this parameter. POMC was not secreted into the fetal circulation at term, but was present in very high levels in amniotic fluid. The highest levels of POMC were present in the retroplacental blood where the values were 35 times higher than in maternal blood; by comparison, corticotrophin releasing hormone and ACTH values in this compartment were twice or equal to those in the maternal blood. CONCLUSION Placental POMC secretion increases during the first half of pregnancy and reaches a plateau from the 20th week to delivery. The inverse correlation between POMC and hCG plasma levels, and very high POMC levels at the feto-maternal interface suggest a physiological role for this precursor during pregnancy.
Isocitrate dehydrogenase mutations: A challenge to traditional views on the genesis and malignant progression of gliomas

Isocitrate dehydrogenases (IDHs) convert isocitrate to α‐ketoglutarate by oxidative decarboxylation and are thereby involved in multiple metabolic processes. Mutations in the genes encoding IDH1 and IDH2 were first reported in human gliomas in 2008 and later on also identified in a minority of patients with acute myeloid leukemia. The mutations universally affect codons 132 in IDH1 and 172 in IDH2 and result in decreased enzymatic activity. The oncogenic pathway triggered by IDH mutations may involve the activation of hypoxia‐inducible factor pathway as well as the acquisition of a novel (gain of enzymatic) function consuming NADPH and generating α‐hydroxyglutarate. Most intriguingly, IDH mutations are observed in ∼70–80% of grade II/III gliomas and the majority of secondary glioblastomas, but only 10% of primary glioblastomas, suggesting a different cellular origin of the gliomas, which had previously been viewed as a multistep process of malignant progression. Understanding the oncogenic pathway mediated by mutant IDH might result in the development of novel, tailored pharmacological therapies for human glioma patients. © 2011 Wiley‐Liss, Inc.
Fragmented Pictures Revisited: Long-Term Changes in Repetition Priming, Relation to Skill Learning, and the Role of Cognitive Resources

Background: Whereas age-related declines in declarative memory have been demonstrated in multiple cross-sectional and longitudinal studies, the effect of age on non-declarative manifestations of memory, such as repetition priming and perceptual skill learning, are less clear. The common assumption, based on cross-sectional studies, is that these processes are only mildly (if at all) affected by age. Objective: To investigate long-term changes in repetition priming and age-related differences in identification of fragmented pictures in a 5-year longitudinal design. Method: Healthy adults (age 28–82 years) viewed drawings of objects presented in descending order of fragmentation. The identification threshold (IT) was the highest fragmentation level at which the object was correctly named. After a short interval, old pictures were presented again along with a set of similar but novel pictures. Five years later the participants repeated the experiment. Results: At baseline and 5-year follow-up alike, one repeated exposure improved IT for old (priming) and new (skill acquisition) pictures. However, long-term retention of priming gains was observed only in young adults. Working memory explained a significant proportion of variance in within-occasion priming, long-term priming, and skill learning. Conclusion: Contrary to cross-sectional results, this longitudinal study suggests perceptual repetition priming is not an age-invariant phenomenon and advanced age and reduced availability of cognitive resources may contribute to its decline.
Risk factors and risk assessment tools for falls in hospital in-patients: a systematic review.

OBJECTIVE To identify all published papers on risk factors and risk assessment tools for falls in hospital inpatients. To identify clinical risk assessment tools or individual clinical risk factors predictive of falls, with the ultimate aim of informing the design of effective fall prevention strategies. DESIGN Systematic literature review (Cochrane methodology). Independent assessment of quality against agreed criteria. Calculation of odds ratios and 95% confidence intervals for risk factors and of sensitivity, specificity, negative and positive predictive value for risk assessment tools (with odds ratios and confidence intervals), where published data sufficient. RESULTS 28 papers on risk factors were identified, with 15 excluded from further analysis. Despite the identification of 47 papers purporting to describe falls risk assessment tools, only six papers were identified where risk assessment tools had been subjected to prospective validation, and only two where validation had been performed in two or more patient cohorts. CONCLUSIONS A small number of significant falls risk factors emerged consistently, despite the heterogeneity of settings namely gait instability, agitated confusion, urinary incontinence/frequency, falls history and prescription of 'culprit' drugs (especially sedative/hypnotics). Simple risk assessment tools constructed of similar variables have been shown to predict falls with sensitivity and specificity in excess of 70%, although validation in a variety of settings and in routine clinical use is lacking. Effective falls interventions in this population may require the use of better-validated risk assessment tools, or alternatively, attention to common reversible falls risk factors in all patients.
Violence and severe mental illness: the effects of substance abuse and nonadherence to medication.

OBJECTIVE Violent behavior among individuals with severe mental illness has become an important focus in community-based care. This study examines the joint effect of substance abuse and medication noncompliance on the greater risk of serious violence among persons with severe mental illness. METHOD Involuntarily admitted inpatients with severe mental illness who were awaiting a period of outpatient commitment were enrolled in a longitudinal outcome study. At baseline, 331 subjects underwent an extensive face-to-face interview. Complementary data were gathered by a review of hospital records and a telephone interview with a family member or other informant. These data included subjects' sociodemographic characteristics, illness history, clinical status, medication adherence, substance abuse, insight into illness, and violent behavior during the 4 months that preceded hospitalization. Associations between serious violent acts and a range of individual characteristics and problems were analyzed by using multivariable logistic regression. RESULTS The combination of medication noncompliance and alcohol or substance abuse problems was significantly associated with serious violent acts in the community, after sociodemographic and clinical characteristics were controlled. CONCLUSIONS Alcohol or other drug abuse problems combined with poor adherence to medication may signal a higher risk of violent behavior among persons with severe mental illness. Reduction of such risk may require carefully targeted community interventions, including integrated mental health and substance abuse treatment.
ATM-Mediated Phosphorylations Inhibit Mdmx/Mdm2 Stabilization by HAUSP in Favor of p53 Activation

The p53 tumor suppressor protein has a major role in protecting genome integrity. Under normal circumstances Mdmx and Mdm2 control the activity of p53. Both proteins inhibit the transcriptional regulation by p53, while Mdm2 also functions as an E3 ubiquitin ligase to target both p53 and Mdmx for proteasomal degradation. HAUSP counteracts the destabilizing effect of Mdm2 by direct deubiquitination of p53. Subsequently, HAUSP was shown to deubiquitinate Mdm2 and Mdmx, thereby stabilizing these proteins. The ATM protein kinase is a key regulator of the p53 pathway in response to double strand breaks (DSBs) in the DNA. ATM fine-tunes p53's response to DNA damage by directly phosphorylating it, by regulating additional post-translational modifications of this protein, and by affecting two p53 regulators: Mdm2 and Mdmx. ATM directly and indirectly induces Mdm2 and Mdmx phosphorylation, resulting in decreased activity and stability of these proteins. We recently provided a mechanism for the reduced stability of Mdm2 and Mdmx by showing that ATM-dependent phosphorylation lowers their affinity for the deubiquitinating enzyme HAUSP. Altogether, the emerging picture portrays an elaborate, but fine-tuned, ATM-mediated control of p53 activation and stabilization following DNA damage. Further insight into the mechanism by which ATM switches the interactions between HAUSP, Mdmx, Mdm2 and p53, to favor p53 activation may offer new tools for therapeutic intervention in the p53 pathway for cancer treatment.