Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences between office and ambulatory blood pressures in children and adolescents attending a hospital hypertension clinic

Background and objectives: Information on ambulatory blood pressure monitoring (ABPM) in children is scarce. While in adults office BP (OBP) is higher than ABP and the difference increases as OBP increases, information in children suggests that at this young age ABP is no lower and often higher than OBP. This study was aimed at describing OBP–ABP differences in a cohort of children of different ages and BPs, and investigating whether OBP–ABP differences are dependent on age or OBP level. Methods: We retrospectively compared OBP and 24-h, daytime and night-time ABP in 433 children and adolescents aged 4–18 years, referred to our hospital clinic. Results: OBP was found to be significantly lower than 24-h and daytime ABP in the low age tertile (4–10 years) but not in the medium and high tertiles. OBP was also lower than ABP in normotensive patients (n = 182), but higher than ABP in untreated hypertensive patients (n = 92) despite similar ages. Continuous analyses showed a weak correlation of OBP–ABP differences with age, and a much stronger correlation with OBP so that 24-h ABP was higher than OBP at OBP values less than 117/73 mmHg and lower than OBP at higher OBP values. Logistic regression analysis indicates that also in children OBP accounts for most of the OBP–ABP difference. Conclusion: There is a common relation both in children and adults between OBP and ABP. It is only because high OBP is common in the elderly, and the lowest OBP is usually found in young children that large positive OBP–ABP differences have been associated with old age, and negative differences with childhood. OBP–ABP differences, often defined as white-coat effect, can have different directions and are likely to be largely due to regression to the mean.
Transcription and Induction Profiles of Three Novel P450 Genes in Liposcelis bostrychophila (Psocoptera: Liposcelididae)

ABSTRACT The cDNAs of three novel P450 genes, CYP4CB1, CYP4CC1, and CYP4CD1 (GenBank accessions EU979550, EU979549, and EU979551, respectively), were sequenced and characterized from the psocid Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae). CYP4CB1, CYP4CC1, and CYP4CD1 contain open reading frames of 1533, 1512, and 1536 nucleotides that encode 511, 504, and 512 amino acid residues, respectively. The putative proteins of CYP4CB1, CYP4CC1, and CYP4CD1 show predicted molecular mass of 59.65, 58.87, and 59.71 kDa, with a theoretical isoelectric point of 6.59, 8.80, and 8.84, respectively. The N-terminal transmembrane domain was only found in CYP4CB1 suggested it is a typical microsomal P450. Phylogenetic analysis showed a close relationship of CYP4CB1, CYP4CC1, and CYP4CD1 with CYP4AW1, CYP4L4, and CYP4E2. Quantitative real-time reverse transcriptase-polymerase chain reaction indicated that these three genes were expressed at all tested developmental stages. In addition, the highest expression occurred in the adult stage, which suggested that these three P450 genes may play important roles in adulthood. The transcripts of CYP4CB1 and CYP4CC1 in adult psocids could be induced to the highest level at 36 and 24 h after the exposure to deltamethrin and paraoxon-methyl (50% lethal concentration [LC50]), respectively, whereas CYP4CD1 remained unchanged. CYP4CD1 transcripts, however, increased rapidly at 8 h after aldicarb (LC50) induction and reached the peak at 36 h. The induction profiles of the three P450 genes suggested that CYP4CB1 and CYP4CC1 are possibly associated with deltamethrin and paraoxonmethyl metabolism in psocids, whereas CYP4CD1 is probably involved in aldicarb metabolism. However, our assumption needs to be further verified by recombinant protein expression of these proteins as well as RNA interference of these genes.
Validation Study of Genetic Associations with Coronary Artery Disease on Chromosome 3q13‐21 and Potential Effect Modification by Smoking

The CATHGEN study reported associations of chromosome 3q13‐21 genes (KALRN, MYLK, CDGAP, and GATA2) with early‐onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype‐smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non‐smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re‐analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.
Failing to Forget: Inhibitory Control Deficits Compromise Memory Suppression in Posttraumatic Stress Dis...

Most people have experienced distressing events that they would rather forget. Although memories of such events become less intrusive with time for the majority of people, those with posttraumatic stress disorder (PTSD) are afflicted by vivid, recurrent memories of their trauma. Often triggered by reminders in the daily environment, these memories can cause severe distress and impairment. We propose that difficulties with intrusive memories in PTSD arise in part from a deficit in engaging inhibitory control to suppress episodic retrieval. We tested this hypothesis by adapting the think/no-think paradigm to investigate voluntary memory suppression of aversive scenes cued by naturalistic reminders. Retrieval suppression was compromised significantly in PTSD patients, compared with trauma-exposed control participants. Furthermore, patients with the largest deficits in suppression-induced forgetting were also those with the most severe PTSD symptoms. These results raise the possibility that prefrontal mechanisms supporting inhibitory control over memory are impaired in PTSD.
Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial.

314 Background: Small bowel adenocarcinoma (SB-ACA) is rare, having little prospective data guiding management. A prior phase I study evaluated UGT1A1 genotype specific dosing of oxaliplatin, irinotecan, and capecitabine. Our prospective, multicenter clinical trial assessing tumor response in pts having metastatic SB-ACA, used a similar dosing strategy. METHODS Genotypes were determined via central lab. Previously untreated pts were dosed by UGT1A1*28 genotypes 6/6, 6/7, and 7/7 receiving 100/85/85 mg/m2 oxaliplatin d1, 150/150/75 mg/m2 irinotecan d1, and 1600/400/200 mg/m2 capecitabine (BID) d2-15 of 21 days. The study design was such that 1 confirmed response in 16 pts expanded enrollment to 33 pts, with 7 required for demonstrating efficacy. RESULTS 28 pts (13-6/6, 10-6/7, 5-7/7) have been enrolled [75% male, mean age 62.5 (range 41-77)]. Location of primary included: duodenum (63%), jejunum (26%), and ileum (7%), with pts having >1 metastatic site (abdominal-41%, bone-7%, liver-56%, lung-30%, nodal-52%, subcutaneous-4%, other-19%). Gr 3+ treatment related toxicity was not significantly different by genotype (50%-6/6, 44%-6/7, 20%-7/7, p=0.48) and included (pts): diarrhea(5), vomiting(5), leukopenia(5), neutropenia(7), and nausea(6). 57% (13 of 23) pts achieved responses during therapy, with a confirmed response rate of 39% (95% CI 0-58%). 18 have died, with a median follow-up of 8.3 mos (range 0-43). CONCLUSIONS UGT1A1 genotype directed dosing with oxaliplatin, irinotecan, and capecitabine appears to result in prolonged response in this population. Larger studies are needed to determine comparability to CapeOx alone or if response/toxicity differs among genotypes. Supported by NIH Grant CA25224, Sanofi-Aventis, and Pfizer. [Table: see text].
Clinical and molecular epidemiology of norovirus infection in childhood diarrhea in China

A prospective investigation was carried out among pediatric outpatients and inpatients with acute non‐dysenteric diarrhea between August, 2008 and July, 2009 in Shanghai, Hangzhou, Chongqing, and Tianjin, China. One step real‐time RT‐PCR was used for detection of norovirus (NoV) genogroups I and II (GI, GII). The NoV genotypes were classified based on partial capsid sequences. Rotavirus (RV) was detected in parallel. Among 4,123 fecal samples from outpatients, 1,067 (25.9%) were NoV‐positive, of which 1,051 (98.5%) belonged to GII and 1,309 (31.7%) were RV‐positive. In the inpatient group (n = 317), 25.6% were NoV‐positive and 41.6% were RV‐positive. Four hundred and fifty‐one out of 1,067 NoV‐positive strains were sequenced and genotyped and 6 typed strains were GI (3 GI.3, 2 GI.5, 1 GI.4) and 445 typed strains were GII. GII strains clustered into nine genotypes including GII.4 2006b (69.2%), the only GII.4 variant identified in this study, followed by GII.3 (23.8%), GII.6 (3.6%), GII.12 (1.3%), GII.2 (0.9%), GII.13 (0.4%), GII.14 (0.2%), GII.7 (0.2%), and GII.16 (0.2%). A peak of NoV infections was observed during the cold season in Tianjin, while NoV activity was higher between late summer and autumn and lower during winter in Shanghai, Hangzhou, and Chongqing. NoV is a common causative agent of childhood diarrhea in China and the seasons of NoV‐associated diarrhea varies between regions. The results show that NoV GII.4 2006b was the predominant strain circulating in China between 2008 and 2009. J. Med. Virol. 84:145–151, 2011. © 2011 Wiley Periodicals, Inc.
Optimization of a glycoengineered Pichia pastoris cultivation process for commercial antibody production

Glycoengineering enabled the production of proteins with human N‐linked glycans by Pichia pastoris. This study used a glycoengineered P. pastoris strain which is capable of producing humanized glycoprotein with terminal galactose for monoclonal antibody production. A design of experiments approach was used to optimize the process parameters. Followed by further optimization of the specific methanol feed rate, induction duration, and the initial induction biomass, the resulting process yielded up to 1.6 g/L of monoclonal antibody. This process was also scaled‐up to 1,200‐L scale, and the process profiles, productivity, and product quality were comparable with 30‐L scale. The successful scale‐up demonstrated that this glycoengineered P. pastoris fermentation process is a robust and commercially viable process. © 2011 American Institute of Chemical Engineers Biotechnol. Prog. , 2011
ABPA in adulthood: a CFTR-related disorder

In Western countries, allergic bronchopulmonary aspergillosis (ABPA) in childhood is very unusual beyond the context of cystic fibrosis (CF). It is presumed to be different in adulthood, although three studies1–3 reported an increased frequency of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in adults with ABPA. Out of the 63 patients investigated in these studies, none was reported as pancreatic insufficient, all had sweat chloride values <60 mmol/l, only two carried the intron 8 splice variant 5T and a single patient was found to be compound heterozygous for two CFTR mutations. However, Miller et al studied only 10 patients and did not sequence all CFTR exons, while the two other reports, including one from our institution, were hampered by the small number of mutations initially looked for …
Factor V Is Complexed with Multimerin in Resting Platelet Lysates and Colocalizes with Multimerin in Platelet α-Granules (*)

Factor V stored in platelets is an important source of factor Va for the prothrombinase complex. Investigations of potential platelet factor Va-binding proteins, using factor Va light chain affinity chromatography, identified a disulfide-linked multimeric protein with a reduced mobility of 155 kDa in the column eluate. Immunodepletion and immunoblotting indicated that this protein was multimerin. Multimerin specifically bound factors V and Va and the isolated factor Va light chain, but not the heavy chain of factor Va. Factor V stored in platelets, but not plasma factor V, was found to be complexed with multimerin. Multimerin immunodepletion of resting platelet lysates was associated with the removal of factor V and the loss of factor V coagulant activity. Immunoelectron microscopic studies colocalized factor V with multimerin in the α-granules of resting platelets. With thrombin-induced platelet activation, we observed dissociation of factor Va-multimerin complexes, multimerin-independent membrane binding of factor Va, and prothrombinase activity that was not inhibitable by multimerin antibodies. This study indicates that platelet factor V is stored as a complex with multimerin and suggests a possible role for multimerin as a carrier protein for factor V stored in platelets.
Effects of two Types of Self-Regulatory Instruction Programs on Students with Learning Disabilities in Writing Products, Processes, and Self-Efficacy

We examined the differential effects of the social cognitive model of sequential skill acquisition (SCM intervention) and the self-regulated strategy development model (SRSD intervention) for writing. One hundred and twenty-one 5th- and 6th- grade Spanish students with learning disabilities (LD) and/or low achievement (LA) were randomly assigned either to an experimental intervention group or the standard instruction group. Both self-regulatory interventions showed a significant improvement with a large effect size in the structure, coherence, and quality of students' writing products, as determined in terms of reader- and text-based measures. Additionally, both interventions demonstrated a substantial increase in the time students spent on writing and revising their texts; the latter was noted especially in the SCM intervention group although only the SRSD intervention showed a significant increase in the time students dedicated to planning text. Finally, with regard to writing self-efficacy, only the SCM intervention group experienced a significant improvement.
Organizational Structure and Product Market Competition

This paper explores the link between delegation of authority and product market competition. It considers a firm that is contemplating entering a market served by an incumbent. The firm can adopt either a decentralized or a centralized authority structure. In the former, authority is delegated to an agent, while in the latter, it is retained by the principal. We address the questions of how the toughness of future product market competition affects the delegation decision, and how this decision in turn affects product market competition. The delegation decision is determined by a trade‐off between inducing the agent to take greater initiative and accepting lower operating profits from a less efficient decision taken by the agent.
Neoadjuvant Chemotherapy with Gemcitabine-Containing Regimens in Patients with Early-Stage Non-small Cell Lung Cancer

Background: Surgical resection alone remains suboptimal for patients with early-stage (I or II) non-small cell lung cancer. Two similar randomized phase II trials were conducted to define an active preoperative regimen in this disease state. Methods: In the first study, patients were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1 (GC) or gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1 (GCb). In the second trial, patients received the same regimen of GCb or gemcitabine 1000 mg/m2 on days 1 and 8 plus paclitaxel 200 mg/m2 on day 1 (GP). Cycles were repeated every 21 days for three cycles. The primary end point was pathologic complete response (pCR) rate. Results: Eighty-seven eligible patients were randomized (GC n = 12, GP n = 35, and GCb n = 40), and 71 (82%) underwent surgery after chemotherapy. The confirmed pCR rate was 2.3% (2 of 87, 95% confidence interval 0.3–8.1). Clinical response rate was 28.7%, complete resection rate was 91.5% (65 of 71 patients), and perioperative mortality rate was 2.8%. As of October 2006, median survival for all patients was 45 months (65.5% censored), with 87.2% alive at 1 year and 69.8% alive at 2 years. Discussion: Neoadjuvant chemotherapy with gemcitabine was feasible and well tolerated, and outcomes were similar to other reports of this treatment strategy. However, no regimen achieved the predefined pCR rate that would be sufficient to warrant further evaluation in the phase III setting. This trial design provides an efficient way of providing a rationale for choosing or rejecting regimens of potential value.
Anatomical location of mature GnRH neurons corresponds with their birthdate in the developing mouse

The gonadotropin‐releasing hormone (GnRH) neurons exhibit substantial functional, anatomical, and molecular heterogeneity, which has hampered their thorough examination. This study was undertaken in an effort to understand whether the anatomical distribution of GnRH neurons is related to their developmental history, because such an association may help explain differences within the population. Using bromodeoxyuridine pulse labeling of timed pregnant female mice we labeled dividing cells, including GnRH neuron progenitors in the olfactory placode, throughout the window of GnRH neuron differentiation. Our results indicate that cells that become postmitotic early tend to populate the rostral aspects of the adult GnRH neuron continuum, whereas later‐generated cells tend to settle more caudally; an inside‐out pattern reminiscent of neocortex. These observations suggest that the timing of differentiation influences the ability of postmitotic GnRH neurons to navigate to their adult location, and hence may be important in determining the ultimate wiring of the adult network. Developmental Dynamics 238:524–531, 2009. © 2009 Wiley‐Liss, Inc.
A Study on Gender and Age Differences in Sleep Spindles

In the present work, gender differences in sleep spindle topography were examined in 40 subjects. Their median age was 32 years (range 22–49 years). Spindles were detected from 3,306,060 s of visually scored stage 2 sleep EEG by a previously validated automatic fuzzy detector at 1-second intervals. A total of 271,168 spindles were found from the six EEG channels analyzed. Females showed a significantly higher percentage of spindles in the left frontal channel than males (Fp1-A2; p = 0.026). To confirm that this difference was gender and not age related, the subjects were divided into two age groups. No significant differences in spindle activity of the frontal channels were found between the groups. However, the interindividual spindle variability seemed to be at least as large as that stemming from gender.
Comparison of outcomes among patients aged 80 and over and younger patients with diffuse large B-cell lymphoma: a population based study

Abstract In this retrospective cohort study of 174 consecutive, newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL), clinical and pathological variables, treatment, response and survival were compared for patients aged 80 and over (n = 40) to those under 80. Eastern Cooperative Oncology Group (ECOG) status and International Prognostic Index (IPI) were significantly worse among older patients. Standard treatment was given to only 32.5% of older versus 86.6% of younger patients, and 65% of the elderly did not receive standard therapy. At 12 months, overall and event-free survival were 51.3% (95% confidence interval [CI]: 35–66%) vs. 93% (CI: 88–97%) and 41.9% (CI: 25–58%) vs. 84.8% (CI: 77–90%), for older versus younger patients, respectively. Choice of therapy was significantly associated with survival in the elderly, and low albumin but not comorbidity score was associated with not receiving standard therapy. Patients with DLBCL aged 80 and over are distinct from all other age groups with regard to treatment tolerance. A minority can receive standard therapy, but for the majority, novel therapeutic options are needed.
Using cure models and multiple imputation to utilize recurrence as an auxiliary variable for overall survival

Background Intermediate outcome variables can often be used as auxiliary variables for the true outcome of interest in randomized clinical trials. For many cancers, time to recurrence is an informative marker in predicting a patient's overall survival outcome and could provide auxiliary information for the analysis of survival times. Purpose To investigate whether models linking recurrence and death combined with a multiple imputation procedure for censored observations can result in efficiency gains in the estimation of treatment effects and be used to shorten trial lengths. Methods Recurrence and death times are modeled using data from 12 trials in colorectal cancer. Multiple imputation is used as a strategy for handling missing values arising from censoring. The imputation procedure uses a cure model for time to recurrence and a time-dependent Weibull proportional hazards model for time to death. Recurrence times are imputed, and then death times are imputed conditionally on recurrence times. To illustrate these methods, trials are artificially censored 2 years after the last accrual, the imputation procedure implemented, and a log-rank test and Cox model used to analyze and compare these new data with the original data. Results The results show modest, but consistent gains in efficiency in the analysis using the auxiliary information in recurrence times. Comparison of analyses show the treatment effect estimates and log-rank test results from the 2-year censored imputed data to be in between the estimates from the original data and the artificially censored data, indicating that the procedure was able to recover some of the lost information due to censoring. Limitations The models used are all fully parametric, requiring distributional assumptions of the data. Conclusions The proposed models may be useful in improving the efficiency in estimation of treatment effects in cancer trials and shortening trial length.
Engaging the student: Programming solving real-life problems

Having taught software development at tertiary level for the past 20 years, the author has found that one of the key concepts that students struggle with is to progress from programming basic constructs like FOR-loops to solving real engineering problems. Once students have mastered the basic programming constructs they fall into the rut of the cookiecutters due to the lack of “seeing” the bridge between theory and practice or in this case construct and application. At Tshwane University of Technology the focus is on vocational training and solving this dilemma is key to the University's mission. Having exhausted efforts in promoting the philosophy of Logical Thinking, Analyzing Sequential Actions and Visual Programming Environments a new initiative in sustainable engineering training is making new inroads to addressing this issue. A new visual simulated virtual world has been created where students now have to write control software to manipulate items within this virtual world. Access to the simulated world can either be through a computer terminal connected to the World Wide Web or through an application running on an Android platform. Together with an artificial intelligent tutoring platform the engagement of students with the virtual world is showing that students are crossing over to become programmers of note and no longer mere cookie-cutters.