Miracle-dz/UniFAR-FTUs huggingface dataset:
Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children.

OBJECTIVE To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). METHOD Infants and young children </=2 years of age with RSV LRI of </=4 days duration, and respiratory scores >/=2. 5 were enrolled. RESULTS One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 </=85% at entry than did placebo recipients, but a higher proportion of placebo recipients required intensive care unit (ICU) care and mechanical ventilation at study entry. The mean RSV hospital stay was 5.52 +/- 0.69 days (SE) for placebo and 4.58 +/- 0.40 days for RSVIG. Additionally, there was an interaction between treatment group and entry respiratory score, which led to subgroup analysis. Children with modest respiratory illness did not receive any benefit from RSVIG therapy. RSVIG recipients with more severe illness (entry respiratory scores >/=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. CONCLUSION RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.
The passive voice in scientific writing. The current norm in science journals

In contrast to past consensus, many authors now feel that the passive voice compromises the quality of scientific writing. However, studies involving sci- entific articles are rare. Using a corpus of 60 scientific research articles from six journals, this study examined the proportion of passives used, and the contexts and forms in which they occurred. The results revealed that about 30% of all clauses were passive clauses. The canonical form was most pervasive, followed by the bare passive; together, they constituted more than a quarter of all clauses analyzed. Passives were typically used in main clauses, followed by relative and adverbial clauses. Roughly 29% of all passives were located in the methodology section. Based on the results, the proportion of passives in scientific writing may stabilize at about 30%. It is unlikely to dramatically drop any further since the trend suggests that passives are still widely used in the methodology section.
Does Near-Infrared Spectroscopy Identify Asphyxiated Newborns at Risk of Developing Brain Injury During Hypothermia Treatment?

Abstract Objective The aim of this article is to assess whether near-infrared spectroscopy (NIRS) identifies, during hypothermia treatment, the asphyxiated newborns who later develop brain injury. Study Design In this study, asphyxiated newborns, for whom later brain injury was defined by brain imaging and/or autopsy results, were monitored by NIRS during therapeutic hypothermia. We compared regional cerebral oxygenation saturation (rSO2) measured by NIRS at key time points for newborns who developed or did not develop later brain injury. Results A total of 18 asphyxiated newborns treated with hypothermia were enrolled. rSO2 was higher in the asphyxiated newborns who developed later brain injury. Sensitivity within the first 10 hours of hypothermia treatment for an adverse outcome was 100% (95% confidence interval [CI], 70–100%) and specificity was 83% (95% CI, 36–99%). Conclusions NIRS appears to identify asphyxiated newborns at risk of developing brain injury as early as the first 10 hours of hypothermia treatment. Thus, NIRS may have an important role as an early outcome predictor in this population.
Ki67 Labeling Index in Neuroendocrine Tumors of the Gastrointestinal and Pancreatobiliary Tract: To Count or Not to Count Is Not the Question, But Rather How to Count

The paper by Tang et al 1 in this issue of American Journal of Surgical Pathology brings a new dimension to the debate on the routine use of Ki67 in the diagnosis of gastrointestinal and pancreatobiliary tract neuroendocrine tumors (GIPNETs). Foremost, the authors underscore that not counting is no longer an option in the diagnosis and management of GIPNETs. Secondly, their results highlight that there may not be an easy solution: the “eyeballing” approach is not acceptable; users will have to choose one of the more reliable albeit cumbersome methods. The issue of Ki67 has various interesting aspects that are worth a critical reappraisal.
Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis

Significance Proper insulin signaling is necessary for regulating glucose metabolism and is often deregulated in cancer. Insulin activation of the phosphoinositide-3 kinase (PI3K) pathway is negatively regulated by the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). We previously described a novel inhibitor of PTEN activity, phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). Here, we show that P-REX2 inhibition of PTEN occurs through the pleckstrin homology (PH) domain and requires PTEN C-terminal tail phosphorylation. Furthermore, loss of Prex2 results in reduced insulin signaling and increased Pten activity, and mice lacking P-rex2 display impaired glucose uptake and insulin resistance. This reveals a crucial role for the PH domain of P-REX2 in the regulation of glucose metabolism through the inhibition of PTEN. Insulin activation of phosphoinositide 3-kinase (PI3K) signaling regulates glucose homeostasis through the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3). The dual-specificity phosphatase and tensin homolog deleted on chromosome 10 (PTEN) blocks PI3K signaling by dephosphorylating PIP3, and is inhibited through its interaction with phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). The mechanism of inhibition and its physiological significance are not known. Here, we report that P-REX2 interacts with PTEN via two interfaces. The pleckstrin homology (PH) domain of P-REX2 inhibits PTEN by interacting with the catalytic region of PTEN, and the inositol polyphosphate 4-phosphatase domain of P-REX2 provides high-affinity binding to the postsynaptic density-95/Discs large/zona occludens-1-binding domain of PTEN. P-REX2 inhibition of PTEN requires C-terminal phosphorylation of PTEN to release the P-REX2 PH domain from its neighboring diffuse B-cell lymphoma homology domain. Consistent with its function as a PTEN inhibitor, deletion of Prex2 in fibroblasts and mice results in increased Pten activity and decreased insulin signaling in liver and adipose tissue. Prex2 deletion also leads to reduced glucose uptake and insulin resistance. In human adipose tissue, P-REX2 protein expression is decreased and PTEN activity is increased in insulin-resistant human subjects. Taken together, these results indicate a functional role for P-REX2 PH-domain–mediated inhibition of PTEN in regulating insulin sensitivity and glucose homeostasis and suggest that loss of P-REX2 expression may cause insulin resistance.
Reported Sensory Processing of Children with Down Syndrome

ABSTRACT Investigators have identified delays and differences in cognitive, language, motor, and sensory development in children with Down syndrome (DS). The purpose of this study was to determine the parent-reported frequency of sensory processing issues in children with DS aged 3–10 years, and the parent-reported functional impact of those sensory issues. Parents completed the short sensory profile (SSP) and a parent questionnaire (PQ). SSP results revealed a total score definite difference rate of 49%. Highest rates of probable and definite difference were in the low energy/weak, underresponsive/seeks sensation, and auditory filtering subsections of the SSP. Themes were generated from responses on the PQ regarding the functional impact of sensory differences on occupational performance in their children with DS, and related strategies currently used by parents. Findings from the study provide information to parents and health care professionals regarding sensory processing patterns in children with DS, and provide foundational data for future research.
cipC is important for Aspergillus fumigatus virulence

Aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. We previously observed that the transcription of a cipC‐like gene was increased when A. fumigatus encountered an increased CO2 concentration, as occurs during the infection process. CipC is a protein of unknown function that might be associated with fungal pathogenicity. In this study, the cipC gene was disrupted in A. fumigatus to evaluate its importance for fungal pathogenicity. The gene was replaced, and the germination, growth phenotype, stress responses, and virulence of the resultant mutant were assessed. Although cipC was not essential, its deletion attenuated A. fumigatus virulence in a low‐dose murine infection model, suggesting the involvement of the cipC gene in the virulence of this fungus. This study is the first to disrupt the cipC gene in A. fumigatus.
Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women.

INTRODUCTION Melatonin (MEL) exerts beneficial effects on the gut partly by myorelaxative properties upon the smooth muscle. Its secretion decreases with age, particularly in postmenopausal women. This study was aimed at evaluating the effect of MEL on the symptoms of irritable bowel syndrome (IBS) in this group of patients. MATERIAL AND METHODS The investigations were carried out in 80 postmenopausal women, aged 48-65 years, divided into two equal groups, diagnosed according to Rome Criteria III: i.e. patients with IBS with constipation predominant (IBS-C), and patients with IBS with diarrhoea predominant (IBS-D). The control group (C) included healthy women aged 46-65 years. In all subjects, 6-sulfatoxymelatonin (6-HMS) concentration urine was measured using ELISA assay. Patients in both groups over the course of six months were given melatonin (at a dose of 3 mg fasting and 5 mg at bedtime) or a placebo (double blind trial). Disease activity was evaluated after two, four and six months, using a ten-point scale to assess the main somatic symptoms: visceral pain, abdominal bloating, etc. RESULTS The amounts of 6-HMS urine excretion (μg/24 h) were: C 11.4 ± 3.0, IBS-C 10.2 ± 3.2, IBS-D 14.0 ± 6.3 (p 〈 0.05). Correlation between values of symptoms score and contrary excretion of 6-HMS: IBS-C r = -0.714, IBS-D r = 0.409. After six months in the IBS-C group, the intensity of visceral pain and abdominal bloating had decreased in 70% of patients (p 〈 0.01) and constipation in 50% of patients (p 〈 0.05). Beneficial changes in the IBS-D group were noted in 45% of patients, but this was not better compared to the placebo. CONCLUSIONS Melatonin can be used as part of the treatment of IBS, particularly in patients with constipation-predominant IBS.
Human T-lymphotropic Virus Type I Tax Protein Utilizes Distinct Pathways for p53 Inhibition That Are Cell Type-dependent*

p53 plays a pivotal role in transmitting signals from many forms of genotoxic stress to genes and factors that control the cell cycle and apoptosis. We have previously shown that the human T-lymphotropic virus type I Tax protein can inhibit p53 function. Recently we reported that Tax inhibits p53 function in Jurkat cells and mouse embryo fibroblasts through a mechanism involving the nuclear factor κB pathway and correlates with phosphorylation on serines 15 and 392 of p53. However, several groups have also observed a mechanism that correlates with p300 binding of Tax. To address this controversy and to determine the mechanism by which Tax inhibits p53 function, we examined the activation functions of Tax required for p53 inhibition. In HeLa and H1299 cells the cAMP-response element-binding protein/activating transcription factor activation function is essential, as demonstrated by the Tax mutants M47 and K88A. In addition, expression of exogenous p300 in H1299 cells allows full recovery of p53 transactivation in the presence of Tax. Consistent with p300 being a limiting factor in H1299, Saos-2, and HeLa cells, we found that the level of endogenous p300 is relatively low in these cells compared with Jurkat cells or the human T-lymphotropic virus type I-infected C81 and MT2 cells. Thus our data suggests that Tax utilizes distinct mechanisms to inhibit p53 function that are cell type-dependent.
Risk of Asymptomatic Bacteriuria among People with Sickle Cell Disease in Accra, Ghana

Asymptomatic bacteriuria (ASB) is benign except in certain medical conditions such as pregnancy and immunosuppression. In Ghana, there are hardly any studies on urinary infections among sickle cell disease (SCD) patients, and the few studies carried out in Africa focused on pediatric SCD populations. The current study aimed to investigate the risk of ASB among SCD patients at a tertiary hospital in Ghana. This was a cross-sectional study involving 110 SCD patients and 110 age and sex matched healthy controls. Urine specimens were collected from all the study subjects and analyzed by standard microbiological methods. Demographic information were also collected from the study subjects. The overall ASB prevalence was significantly higher among SCD patients (17.2%) than among the control group (8.2%), and the relative risk was 2.11 (p = 0.0431; CI = 1.00–4.45). Being female was as a predictor of ASB among the SCD patients (OR = 14.76; CI = 11.23–18.29; p = 0.0103). The most common organism isolated from the study participants was coagulase negative Staphylococcus species (4.1%), followed by Escherichia coli (2.7%); etiology of ASB in the SCD patients was more diverse compared to healthy people. All the E. coli isolates were susceptible to amikacin, sparfloxacin and norfloxacin but resistant to ampicillin.
Addressing the challenges of a cross-national investigation: lessons from the Pittsburgh-Pisa study of treatment-relevant phenotypes of unipolar depression

Background: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. Purpose: This report describes how those challenges were met in the study ``Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy. Methods: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems. Results: By having bilingual investigators and staff members who spent time at one another's sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year. Limitations: This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings. Conclusions: The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them. Clinical Trials 2008; 5: 253—261. http://ctj.sagepub. com
Effectiveness of a Handwriting Intervention With At-Risk Kindergarteners.

OBJECTIVE We examined the effectiveness of an occupational therapist-led handwriting intervention for special education and at-risk kindergarteners. METHOD We incorporated a two-group, pretest-posttest design. Both groups consisted of kindergarteners receiving individualized education program (IEP) or Response to Intervention (RtI) support. An occupational therapist provided biweekly group handwriting instruction using the Size Matters Handwriting Program to students in the intervention group (n = 23). The control group (n = 12) received the standard handwriting instruction. RESULTS Students in the intervention group demonstrated significantly greater gains in handwriting legibility than students in the control group. Students in the intervention group also demonstrated significantly greater gains in the prereading skills of uppercase letter recognition, lowercase letter recognition, and letter sound recognition. CONCLUSION This study provides preliminary support for an occupational therapist-led handwriting intervention to improve writing legibility and letter recognition in kindergarteners receiving RtI and IEP supports.
Similar effects of lysine deficiency in muscle biochemical characteristics of fatty and lean piglets

Spanish Ministry of Economy and Competitiveness (MINECO) grant number AGL2011-25360. P. Palma-Granados had a fellowship from the Spanish MICINN FPI Program (BES-2012-053078). We thank M.A. Linan for skillful technical assistance. We are also very grateful to Sanchez Romero Carvajal Jabugo S.A. (El Puerto de Santa Maria, Cadiz, Spain) for providing Iberian purebred experimental animals. Corn gluten meal and corn starch used in this experiment were kindly provided by Tereos Syral (Zaragoza, Spain). The assays described are part of the doctoral thesis of P. Palma-Granados, under the Doctoral Program of Granada University, Spain.
Pubertal timing and depressive symptoms in late adolescence: The moderating role of individual, peer, and parental factors

Abstract This longitudinal study examined personal-accentuation and contextual-amplification models of pubertal timing. In these models, individual and contextual risk factors during childhood and adolescence can magnify the effects of early or late puberty on depression symptoms that occur years later. The moderating role of prepubertal individual factors (emotional problems in late childhood) and interpersonal factors (deviant peer affiliation, early dating, perceived peer popularity, and perceived parental rejection during adolescence) were tested. A representative sample of 1,431 Canadian adolescents between 10–11 and 16–17 years of age was followed biannually. In line with the personal-accentuation model, early puberty has been shown to be a predictor for depression in both girls and boys who presented emotional problems in childhood. This effect was also noted for late maturing boys. Consistent with the contextual-amplification model, early puberty predicted later depression in youth who perceived greater parental rejection. Interpersonal experiences such as early dating in girls and deviant peer affiliation in boys predicted depression in early maturers as well. For girls, early dating was also found to be amplified by childhood emotional problems. In line with biopsychosocial models, results indicate that the effect of pubertal timing on depressive symptoms must be conceptualized through complex interactions between characteristics of adolescents' interpersonal relationships and prepubertal vulnerabilities.
Clientele Change, Persistent Liquidity Shock, and Bond Return Reversals after Rating Downgrades

Analysis of the actual holdings of bond mutual funds and transaction data of insurance companies during the period between 2003 and 2007 confirms a clientele change when a corporate bond is initially downgraded to ? junk? status. Investment-grade bond funds and insurance companies are forced to sell to meet their investment constraints, creating a persistent price concession of around 2%; prices recover partially after almost three months. High-yield bond funds and hedge funds specializing in distressed securities benefit from providing liquidity during these downgrade events. The clientele change is greater for bonds held by more constrained mutual funds. We do not find a persistent liquidity shock around similar downgrades when the threshold between investment grade and speculative grade is not crossed.
Increased Extracellular Serotonin in Rat Brain After Systemic or Intraraphe Administration of Morphine

Abstract: The effect of morphine on serotonin (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in the CNS of unanesthetized rats was investigated by microdialysis. Morphine was administered either subcutaneously, by local perfusion into the diencephalon, or by intraraphe microinjection. Systemic administration of morphine resulted in a significant increase in both extracellular 5‐HT and 5‐HIAA in the diencephalon. The effect of morphine on 5‐HT was dose dependent during local perfusion of the diencephalon with inhibitors of uptake or monoamine oxidase. Systemic morphine also produced significant increases in extracellular 5‐HT in the striatum and hippocampus during uptake inhibition. The site of opioid effects on 5‐HT was tested by locally perfusing morphine into the diencephalon. This had no effect on 5‐HT or 5‐HIAA. In contrast, intraraphe injection of morphine caused a dose‐dependent increase in extracellular 5‐HT and 5‐HIAA in the diencephalon. These results suggest that systemic morphine induces an increase in 5‐HT release in widespread areas of the forebrain. This appears to be due to an effect on 5‐HT cell bodies and not on 5‐HT nerve endings in projection sites.
Evolving trends in the long-term treatment of bipolar disorder

The episodic and chronic nature of bipolar disorder usually requires long-term treatment in all patients, yet there is an unmet need for well-tolerated and clinically effective maintenance therapy with enhanced patient adherence. Few well-tolerated treatment options are currently available that are both effective in all phases of bipolar disorder and prevent recurrence of episodes. Lithium has well-established efficacy in the prevention of further manic episodes and may also be effective in the prevention of depression and suicide, but safety is a concern due to narrow therapeutic window. For valproate and carbamazepine, data appear much less compelling. Lamotrigine has shown to be effective for long-term prevention of depressive episodes. Controlled studies suggest that atypical antipsychotics may also have mood-stabilizing properties and might become standard for long-term therapy in the new future. The role of psychoeducation in improving adherence to medication in long-term treatment and overall patient outcomes is also crucial.