Miracle-dz/UniFAR-FTUs huggingface dataset:
Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid

Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC) but excellent response is not observed in all cases. Since potential favourable effects of fibrates have been reported in short series with inconclusive results, we have carried out a pilot study to analyse the effects of bezafibrate in patients with suboptimal response to UDCA.
The Pharmacokinetics of Colistin in Patients with Cystic Fibrosis

The safety and pharmacokinetics ofcolistin were determined after first dose (n = 30) and again under steady‐state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half‐life (t1/2), mean residence time (MRT), steady‐state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first‐dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first‐dose and steady‐state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty‐one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin‐induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin‐induced nephrotoxicity. No relationship between the occurrence of any colistin‐associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.
Clinical evaluation of an automated oscillometric blood pressure wrist device

ObjectivesUp to one-third of all blood pressure devices sold are for measurement at the wrist. Wrist monitors are thought to be subject to errors associated with movement and incorrect posture. We used the British Hypertension Society protocol to determine the accuracy of the Omron Rx automated wrist blood pressure monitor in adults. We also investigated the errors associated with miscuffing and posture with measurements at the wrist compared to the upper arm. MethodsThe study was conducted at a large teaching hospital in the UK. Participants 18 years and over were eligible for inclusion. Exclusion criteria were cardiac arrhythmias and inaudible Korotkoff sounds. Eighty-five participants were selected for the main validation study. Thirty-four subjects took part in the study investigating miscuffing issues and 15 subjects were included in the study investigating postural errors. ResultsThe Omron Rx achieved an overall grade B according to the British Hypertension Society Protocol. The mean differences (standard deviation) between the observers and the device were 0.3 (9.0) and 2.5 (8.8) mmHg for systolic and diastolic blood pressure respectively. In the medium and high-pressure ranges (≥130/80 mmHg) the device achieved a grade C. When used at home the mean blood pressure reading over 60 measurements in 15 subjects was 123/75 mmHg when taken with the Omron Rx and 124/77 mmHg when taken with the automated upper arm device with no significant difference in the standard deviation of the readings. When compared with mercury sphygmomanometry using both a medium and large cuff, the wrist device readings were closest to the mercury measurements when the most appropriately sized cuff was used. ConclusionsThe Omron Rx wrist monitor is accurate according to the British Hypertension Society protocol, but narrowly fails the Association of the Advancement of Medical Instrumentation criteria. Measurements at the wrist are not associated with miscuffing errors. Use of the wrist device by patients in the home setting gives comparable readings to a standard upper arm device.
Cooperation as Joint Action

Abstract The paper studies cooperation as joint action, where joint action can, first, be conceptualized either individualistically in terms of the participants' individual goals and beliefs that the joint action is taken to serve. This is individualistic or ‛I-mode’ cooperation. Special version of it is ‛ pro-group I-mode’ cooperation, where the goals are shared. Second, cooperation can be of the kind where a group of persons act together as a group in terms of the non-aggregative ‛ we’ that they form. The results of the paper support the conjecture that we-mode conceptualization and an account of cooperation is needed to complement the individualistic (pro-group) I-mode account(s) in social science theorizing and experimentation.
CHILDHOOD-ONSET DIABETES AND THE RISK OF RETINOPATHY 20 YEARS LATER Short running title : Ketoacidosis at diagnosis and diabetic retinopathy

Silvana Salardi, MD, Massimo Porta, MD, PhD, Giulio Maltoni, MD, Franco Cerutti, MD, Silvia Rovere, MD, Dario Iafusco, MD, Stefano Tumini, MD, Vittoria Cauvin, MD, Stefano Zucchini, MD, Francesco Cadario, MD, Giuseppe d6Annunzio, MD, Sonia Toni, MD Alessandro Salvatoni, MD, Maria Antonietta Zedda, MD, Riccardo Schiaffini, MD, for the Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED)
Retro‐Enantio N‐Methylated Peptides as β‐Amyloid Aggregation Inhibitors

An emerging and attractive target for the treatment of Alzheimer's disease is to inhibit the aggregation of β‐amyloid protein (Aβ). We applied the retro‐enantio concept to design an N‐methylated peptidic inhibitor of the Aβ42 aggregation process. This inhibitor, inrD, as well as the corresponding all‐L (inL) and all‐D (inD) analogues were assayed for inhibition of Aβ42 aggregation. They were also screened in neuroblastoma cell cultures to assess their capacity to inhibit Aβ42 cytotoxicity and evaluated for proteolytic stability. The results reveal that inrD and inD inhibit Aβ42 aggregation more effectively than inL, that inrD decreases Aβ42 cytotoxicity to a greater extent than inL and inD, and that as expected, both inD and inrD are stable to proteases. Based on these results, we propose that the retro‐enantio approach should be considered in future designs of peptide inhibitors of protein aggregation.
Exogenous hormone use and meningioma risk

The decision to commence or continue use of hormone replacement therapy or oral contraceptives in women presumed or known to be diagnosed with intracranial meningioma is a common clinical question in neurosurgery. A review of the English‐language literature was undertaken to examine the association between the use of exogenous hormones and meningioma risk. Seven publications were identified, 6 of which met criteria for inclusion. No randomized clinical trial data were available, hence, results were collected from 2 population‐based case‐control studies, 2 hospital‐based case‐control studies, 1 nested case‐control study drawn from a large national cohort, and 1 retrospective cohort study. At present, there is no statistical evidence of an increased risk of meningioma among users of oral contraceptives. Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk. Further evaluation of exogenous hormone use in women with meningioma is needed with particular attention to stratification by hormone (ie, estrogen and/or progesterone) composition, duration of and age at use as well as tumor receptor subtype. Cancer 2007. © 2007 American Cancer Society.
Thyroid‐associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study

Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population‐based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO‐Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO‐Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO‐Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4‐related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO‐Ab level, and TPO‐Ab‐related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid‐related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.
Pre-existing Distortions in Nucleic Acid Structure Aid Polypurine Tract Selection by HIV-1 Reverse Transcriptase*

Precise cleavage at the polypurine tract (PPT)/U3 junction by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase RNase H is critical for generating a correct viral DNA end for subsequent integration. Using potassium permanganate (KMnO4) modification, we have identified a significant distortion in the nucleic acid structure at the HIV-1 PPT/U3 junction in the absence of trans-acting factors. Unusually high reactivity of template thymine +1 is detected when the PPT primer is extended by DNA or RNA at its 3′ terminus. Chemical footprinting suggests that the extent of base unstacking in the wild-type species is comparable when the +1 A:T base pair is replaced by a C:T mismatch. However, reactivity of this template base is diminished after alterations to upstream (rA)4:(dT)4 or (rG)6:(dC)6 tracts. Importantly, there is a correlation between the structural deformation at base pair +1 and precise cleavage at the PPT/U3 junction by HIV-1 reverse transcriptase/RNase H. KMnO4 modification also revealed unusually high reactivity for one of two (dT)4:(rA)4 duplexes upstream of the PPT/U3 junction, suggesting a significant structural distortion within the PPT itself in the absence of the retroviral polymerase. Structural abnormalities in this region are not only essential for resistance of the PPT to hydrolysis but also significantly impact the conformation of the PPT/U3 junction. Our data collectively suggest that the entire PPT sequence contributes to the structural distortion at the PPT/U3 junction, potentially providing a mechanism for its selective processing.
Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion

Human mitochondrial DNA (mtDNA) encodes 13 proteins involved in oxidative phosphorylation (OXPHOS). In order to investigate the role of mitochondrial OXPHOS genes in breast tumorigenesis, we have developed a breast epithelial cell line devoid of mtDNA (ρ0 cells). Our analysis revealed that depletion of mtDNA in breast epithelial cells results in in vitro tumorigenic phenotype as well as breast tumorigenesis in a xenograft model. We identified two major gene networks which were differentially regulated between parental and ρ0 epithelial cells. The focal proteins in these networks include i) FN1 (fibronectin) and ii) p53. Bioinformatic analyses of FN1 network identified laminin, integrin and 5 of 6 members of peroxiredoxin whose expression were altered in ρ0 epithelial cells. In the p53 network, we identified SMC4 and WRN whose changes in expression suggest that this network may affect the chromosomal stability. Consistent with above finding our study revealed an increase DNA double strand breaks, and unique chromosomal rearrangements in ρ0 breast epithelial cells. Additionally, we identified tight junction proteins claudin-1 and claudin-7 in p53 network. To determine the functional relevance of altered gene expression, we focused on detailed analyses of claudin-1 and -7 proteins in breast tumorigenesis. Our study determined that i) claudin-1 and 7 were indeed down regulated in ρ0 breast epithelial cells, ii) down regulation of claudin-1 or -7 led to neoplastic transformation of breast epithelial cells, and iii) claudin-1 and -7 were also down regulated in primary breast tumors. Together, our study suggest that mtDNA encoded OXPHOS genes play a key role in transformation of breast epithelial cells and that multiple pathway involved in mitochondria-to-nucleus retrograde regulation contribute to transformation of breast epithelial cells
A Meta-Analysis of Working Memory Deficits in Children With Learning Difficulties

Children with learning difficulties suffer from working memory (WM) deficits. Yet the specificity of deficits associated with different types of learning difficulties remains unclear. Further research can contribute to our understanding of the nature of WM and the relationship between it and learning difficulties. The current meta-analysis synthesized research on verbal WM and numerical WM among children with reading difficulties (RD), children with mathematics difficulties (MD), and children with reading and mathematics difficulties (RDMD). A total of 29 studies subsuming 110 comparisons were included. Results showed that compared to typically developing children, all learning difficulty groups demonstrated deficits in verbal WM and numerical WM, with RDMD children showing the most severe WM deficits. MD children and RD children showed comparable verbal WM deficits, but MD children showed more severe numerical WM deficits than RD children. Neither severity of learning difficulties nor type of academic screening emerged as a moderator of WM deficit profiles. Although the findings indicate the domain-general nature of WM deficits in RD, MD, and RDMD children, the numerical WM deficits of children with MD and RDMD may reflect the domain-specific nature of WM deficits.
Impact of genetic counseling: A review of published follow‐up studies

Retrospective follow‐up studies on the impact of genetic counseling, published since 1970, are reviewed in the present paper. Particular attention has been paid to evaluation of understanding of genetic information, planning of later pregnancies and real changes in family composition. A rather wide divergence was found with regard to these three parameters, probably more related to the design of the studies than to a divergence in counselees' understanding and decisions, emphasizing that more, and especially more methodologically sound studies are necessary to evaluate the impact of genetic counseling.
Technology and Classroom Practices

Abstract This study examines the findings from 174 case studies of innovative pedagogical practices using technology from 28 participating countries. The study looks at how classrooms world-wide are using technology to change the practices of teachers and students. Within many of these classrooms, the use of technological tools and resources supports students as they search for information, design products, and publish results. Teachers create structure, provide advice, and monitor progress. Beyond these commonly exhibited practices, the study identifies specific patterns of classroom practice that are more likely to be associated with reports of certain desirable student outcomes. Examples are provided.
Presence of a thermoregulatory hot spot in the prothorax of the large carpenter bee and the bumble bee

In both the large carpenter bee (Xylocopa pubescens) and the bumblebee (Bombus terrestris), a hot spot was detected in the center of the prothorax on its dorsal‐external aspect. In both cases, the temperature in this hot spot was found to be greater than the ambient temperature and that at the tip of the gaster. In B. terrestris, it was higher by 9–10°C from that at the gaster tip and by 15–16°C from the ambient temperature, while in X. pubescens the corresponding differences were 11–20°C and 18–19°C, respectively. The recorded thermal differences were not fixed but were rather variable, temporally as well as individually, but invariably all individuals measured showed these temperature differences. Furthermore, in none of the studied specimens was a hot spot detected in any part of the body other than the prothorax. From this hot spot in the prothorax, there is a cascade of temperatures in both directions, that is, anteriorly towards the head and posteriorly towards the gaster, with a graded drop in temperature in either direction. This article discusses possible reasons for the existence of such a hot spot in this particular location (the prothorax), its role or function, and its mode of operation. The authors speculate that it is a thermoregulatory center (for heating or cooling) that might be present in possibly all Hymenoptera that spend a considerable part of their life flying, regardless of whether they are social, parasocial, or solitary. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Determinants of Economic Growth: A Cross-Country Empirical Study

Research on economic growth has exploded in the past decade. Hundreds of empirical studies on economic growth across countries have highlighted the correlation between growth and a variety of variables. Determinants of Economic Growth, based on Robert Barro's Lionel Robbins Memorial Lectures, delivered at the London School of Economics in February 1996, summarizes this important literature. The book contains three essays. The first is a survey of the research on the determinants of long-run growth through the estimation of panels of cross-country data. The second essay details the interplay between growth and political freedom or democracy and finds some evidence of a nonlinear relationship. At low levels of political rights, an expansion of rights stimulates growth; however, once a moderate level of democracy has been obtained, a further expansion of rights reduces growth. The final essay looks at the connection between inflation and economic growth. Its basic finding is that higher inflation goes along with a lower rate of economic growth.
Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

ABSTRACT Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter), non-ESBL E. coli (MIC90 of ≤0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90 of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained in vitro from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90 values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of Enterobacteriaceae and P. aeruginosa were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.
On the value function of one-dimensional optimal control problems with junctions

We first study a one-dimensional optimal control problem with two controlled different dynamics in two half-lines. This may represent a two-edges node of a network on which we are controlling an evolution with different dynamics on different edges. By the point of view of the dynamic programming, and of the corresponding Hamilton-Jacobi-Bellman equation, the discontinuity of the dynamics at the node is in general a big mathematical problem. We introduce an approximation given by the use of a switching rule of the so-called delayed-relay type, and we study the passage to the limit when the parameter of the approximation goes to zero. Then we apply the same procedure to the case of a junction of three half-lines at one point (a three-edges node of a network).
To Resect or Not to Resect: The Effects of Rib-Sparing Harvest of the Internal Mammary Vessels in Microsurgical Breast Reconstruction

Abstract Background The internal mammary vessels are the most commonly used recipients for microsurgical breast reconstructions. Often, the costal cartilage is sacrificed to obtain improved vessel exposure. In an effort to reduce adverse effects associated with traditional rib sacrifice, recent studies have described less-invasive, rib-sparing strategies. Methods After obtaining institutional review board's approval, a retrospective review of all patients undergoing microsurgical breast reconstruction at a single institution between November 2007 and December 2013 was conducted. Patients were divided into two cohorts for comparison: rib-sacrificing and rib-sparing internal mammary vessel harvests. Results A total of 547 reconstructions (344 patients) met inclusion criteria for this study. A total of 64.9% (n = 355) underwent rib-sacrificing internal mammary vessel harvest. Cohorts were similar in baseline patient characteristics, indications for surgery, and cancer therapies. However, patients undergoing rib-sparing reconstructions had significantly shorter operative times (440 vs. 476 minutes; p < 0.01), and significantly less postoperative pain on postoperative day (POD) 1 (2.8/10 vs. 3.4/10; p = 0.033) and POD2 (2.4/10 vs. 3.0/10; p = 0.037). Furthermore, patients undergoing rib-sparing techniques had greater incidence of fat necrosis requiring excision (12.5 vs. 2.8%; p < 0.01) and a trend toward higher incidence of hematoma, venous thrombosis, and arterial thrombosis when compared with rib-sacrificing patients. Conclusions Rib-sparing harvest of internal mammary vessels is a feasible technique in microsurgical breast reconstruction. However, given the significant increase in fat necrosis requiring surgical excision, the trend toward increased postoperative complications, and no significant difference in postoperative revision rates, the purported benefits of this technique may fail to outweigh the possible risks.