Miracle-dz/UniFAR-FTUs huggingface dataset:
A population‐based study of cancer risk in twins: Relationships to birth order and sexes of the twin pair

One thousand and sixty‐three twins with cancer whose co‐twin was born alive were identified among patients born since September 1939 with cancers incident in England and Wales during 1971–1984 at childhood and young adult ages. Site‐specific risks of cancer were analysed in relation to birth order within the twinship and sexes of the twin pair, using adjusted national birth data to give control distributions of these variables. Risk of leukaemia was increased in first‐born twins, risk of testicular cancer was increased in second‐born twins with female co‐twins but decreased in second‐born twins with male co‐twins and lung cancer risk was increased in first‐born twins with same‐sex co‐twins. Cutaneous melanoma risk was increased in persons with opposite‐sex co‐twins, nervous system cancer risk was increased in females with opposite‐sex co‐twins and Hodgkin's disease risk was increased in persons with same‐sex co‐twins. For most of the findings, no previous comparable analyses are available, so interpretation of the results must be provisional until the analyses can be repeated on other data. The result for leukaemia would accord with previous suggestions that leukaemia may be of prenatal origin and may sometimes lead to intrauterine death. The Hodgkin's disease result would fit with theories of an infectious aetiology, and this view is strengthened by reanalysis of previous data on paralytic poliomyelitis in twins, which show a pattern similar to that for the Hodgkin's disease patients. Cancer risk in relation to birth order and sex of twins can give novel, objective data relating to prenatal and infectious disease aetiology of cancers. © 1996 Wiley‐Liss, Inc.
PRELOAD OPTIMIZATION USING “STARLING CURVE” GENERATION DURING SHOCK RESUSCITATION: CAN IT BE DONE?

Preload-directed resuscitation is the standard of care in U.S. trauma centers. As part of our standardized protocol for traumatic shock resuscitation, patients who do not respond to initial interventions of hemoglobin replacement and fluid volume loading have optimal preload determined using a standardized algorithm to generate a “Starling curve. ” We retrospectively analyzed data from 147 consecutive resuscitation protocol patients during the 24 months ending August 2002. Fifty (34%) of these patients required preload optimization, of which the optimization algorithm was completed in 36 (72%). The average age of those who required preload optimization was 44 ± 3 years vs. 34 ± 1 years for patients who did not. Execution of the algorithm caused PCWP to increase from 18 ± 1 mmHg to a maximum of 25 ± 2 mmHg and CI to increase from 3.2 ± 0.1 L/min m−2 to 4.5 ± 0.4 L/min m−2. Algorithm logic determined PCWP = 24 ± 2 to be optimal preload at the maximum CI = 4.8 ± 0.4, and as the volume loading threshold for the remaining time of the resuscitation process. Starling curve preload optimization was begun 6.5 ± 0.8 h after start of the resuscitation protocol and required 36 ± 5 min and 4 ± 0.4 fluid boluses (1.6 ± 0.2 L). Comparison of early response of those patients who required preload optimization and those who did not indicated hemodynamic compromise apparent in the 1st 4 h of standardized resuscitation. We conclude that preload optimization using sequential fluid bolus and PCWP–CI measurement to generate a Starling curve is feasible during ICU shock resuscitation, but that there is the disadvantage that increasing and maintaining high PCWP may contribute to problematic tissue edema.
Evidence that a sequence similar to TAR is important for induction of the JC virus late promoter by human immunodeficiency virus type 1 Tat

A specific RNA sequence located in the leader of all human immunodeficiency virus type 1 (HIV-1) mRNAs termed the transactivation response element, or TAR, is a primary target for induction of HIV-1 long terminal repeat activity by the HIV-1-derived trans-regulatory protein, Tat. Human neurotropic virus, JC virus (JCV), a causative agent of the degenerative demyelinating disease progressive multifocal leukoencephalopathy, contains sequences in the 5' end of the late RNA species with an extensive homology to HIV-1 TAR. In this study, we examined the possible role of the JCV-derived TAR-homologous sequence in Tat-mediated activation of the JCV late promoter (Tada et al., Proc. Natl. Acad. Sci. USA 87:3479-3483, 1990). Results from site-directed mutagenesis revealed that critical G residues required for the function of HIV-1 TAR that are conserved in the JCV TAR homolog play an important role in Tat activation of the JCV promoter. In addition, in vivo competition studies suggest that shared regulatory components mediate Tat activation of the JCV late and HIV-1 long terminal repeat promoters. Furthermore, we showed that the JCV-derived TAR sequence behaves in the same way as HIV-1 TAR in response to two distinct Tat mutants, one of which that has no ability to bind to HIV-1 TAR and another that lacks transcriptional activity on a responsive promoter. These results suggest that the TAR homolog of the JCV late promoter is responsive to HIV-1 Tat induction and thus may participate in the overall activation of the JCV late promoter mediated by this transactivation.
Inhibition of spinal or hypoglossal motoneurons of the newborn rat by glycine or GABA

The function of GABA or glycine during early postnatal development remains controversial as their action is reported as either excitatory or inhibitory. The present study addressed the question of the functional role of GABA or glycine on rat motoneurons shortly after birth. For this purpose, using in vitro preparations from immature rats (postnatal age, P0‐P4 days), we recorded from lumbar spinal motoneurons and hypoglossal motoneurons. All data were obtained under current clamp conditions (recording with potassium methylsulphate containing electrodes) from cells at about −70 mV resting potential. On spinal motoneurons we used the glycinergic and GABAergic recurrent postsysnaptic potential (PSP) mediated by Renshaw cells to assess its impact on excitatory synaptic inputs from dorsal afferent fibres. Despite its depolarizing nature, the recurrent PSP consistently inhibited synaptic excitation of lumbar motoneurons. On hypoglossal motoneurons, exogenously applied GABA or glycine produced depolarization with decreased input resistance. This response was always associated with inhibition of cell firing induced by intracellular current pulses. Even when the membrane potential was repolarized to resting level in the presence of GABA or glycine, hypoglossal motoneurons failed to generate spikes. Conversely, similar depolarization produced by glutamate consistently facilitated spike firing. GABAergic and glycinergic synaptic potentials evoked by focal stimulation of the reticular formation inhibited firing and/or increased firing latency in the majority of hypoglossal motoneurons. These results indicate that, immediately after birth, rat motoneurons were inhibited by synaptically released or exogenously applied GABA or glycine.
Transimpedance Amplifier for High Sensitivity Current Measurements on Nanodevices

The paper presents a very high sensitivity transimpedance amplifier in standard CMOS 0.35 mum technology suited for sensing current signals from molecular and nanodevices systems. The circuit, based on an integrator followed by a differentiator configuration, features i) a low-noise time-continuous feedback loop to cope with possible standing currents from the device under test as high as few tens of nA without limiting the signal dynamic range; ii) active current-reducers to implement very high value equivalent resistances of hundreds of GOmega with high linearity irrespective to the current direction and characterized by a shot noise current level (2qI) which is, for low standing current, few orders of magnitude smaller than a physical resistor of equal value and iii) nested-Miller compensation networks to ensure strong stability over a bandwidth of few MHz. Thanks to the ability to draw large standing currents, the circuit is suitable for a use in biological systems where physiological medium is co-present. The measured input equivalent noise of 4 fA/radic(Hz) at about 100 kHz, recorded when the input dc current is lower than 10 pA, allows the chip to be used, among others, in impedance spectroscopy measurements at the nanoscale with a capability of detecting capacitance variations in sub-attofarad range to cope with the challenges of single-chip instrumentation.
Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial

Objectives: Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. Design: Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. Settings: ICU of a tertiary care academic center. Patients: One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0–74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0–24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). Interventions: Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations and follow-up until hospital discharge. Measurements and Main Results: Dysphagia screening was positive in 12.4% (n = 116/933) after extubation (18.3% of emergency and 4.9% of elective patients) and confirmed by specialists within 24 hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n = 58/96) remained positive until hospital discharge. Days on feeding tube, length of mechanical ventilation and ICU/hospital stay, and hospital mortality were higher in patients with dysphagia (all p < 0.001). The univariate hazard ratio for 90-day mortality for dysphagia was 3.74 (95% CI, 2.01–6.95; p < 0.001). After adjustment for disease severity and length of mechanical ventilation, dysphagia remained an independent predictor for 28-day and 90-day mortality (excess 90-d mortality 9.2%). Conclusions: Dysphagia after extubation was common in ICU patients, sustained until hospital discharge in the majority of affected patients, and was an independent predictor of death. Dysphagia after mechanical ventilation may be an overlooked problem. Studies on underlying causes and therapeutic interventions seem warranted.
(Mis)Representing the 2008 Prorogation: Agendas, Frames, and Debates in Canada’s Mediacracy

In this article, we explore the role of the Canadian media during the 2008 parliamentary crisis. While the crisis was resolved when the Governor General granted a request for prorogation that allowed the Prime Minister to avoid a vote of no-confidence, debate persists about the wisdom of such action. We argue this event represents an important case study in understanding how the Canadian media communicates essential principles of parliamentary democracy. Five years later, and based on recent research, we compare survey results on the 2008 prorogation between 10 leading Canadian journalists and commentators, and 30 constitutional scholars and former advisers to the Crown. Dans cet article, nous explorons le role joue par les medias canadiens au cours de la crise parlementaire en 2008. Alors que la crise a ete resolue lorsque le gouverneur general a accorde une demande de prorogation qui a permis au premier ministre d’eviter un vote de non-confiance, le debat persiste sur la sagesse d’une telle action. Nous soutenons que cet evenement offre l’occasion de mieux comprendre comment les medias canadiens representent les principes essentiels de la democratie parlementaire. Cinq ans plus tard, et sur la base de recherches recentes, nous comparons les resultats d’une enquete sur la prorogation de 2008 effectuee aupres de 10 journalistes et commentateurs canadiens bien en vue, et 30 professeurs de droit constitutionnel ou anciens conseillers de la Couronne.
Nuclear trafficking of FGFR1: A role for the transmembrane domain

Several members of the fibroblast growth factor (FGF) family lack signal peptide (SP) sequences and are present only in trace amounts outside the cell. However, these proteins contain nuclear localization signals (NLS) and accumulate in the cell nucleus. Our studies have shown that full length FGF receptor 1 (FGFR1) accumulates within the nuclear interior in parallel with FGF‐2. We tested the hypothesis that an atypical transmembrane domain (TM) plays a role in FGFR1 trafficking into the nuclear interior. With FGFR1 destined for constitutive fusion with the plasma membrane due to its SP, how the receptor may enter the nucleus is unclear. Sequence analysis identified that FGFR1 has an atypical TM containing short stretches of hydrophobic amino acids (a.a.) interrupted by polar a.a. The β‐sheet is the predicted conformation of the FGFR1 TM, in contrast to the α‐helical conformation of other single TM tyrosine kinase receptors, including FGFR4. Receptor trafficking in live cells was studied by confocal microscopy via C‐terminal FGFR1 fusions to enhanced green fluorescent protein (EGFP) and confirmed by subcellular fractionation and Western immunoblotting. Nuclear entry of FGFR1–EGFP was independent of karyokinessis, and was observed in rapidly proliferating human TE671 cells, in slower proliferating glioma SF763 and post‐mitotic bovine adrenal medullary cells (BAMC). In contrast, a chimeric FGFR1/R4‐EGFP, where the TM of FGFR1 was replaced with that of FGFR4, was associated with membranes (golgi‐ER, plasma, and nuclear), but was absent from the nucleus and cytosol. FGFR1Δ‐EGFP mutants, with hydrophobic TM a.a. replaced with polar a.a. , showed reduced association with membranes and increased cytosolic/nuclear accumulation with an increase in TM hydrophilicity. FGFR1(TM−)‐EGFP (TM deleted), was detected in the golgi‐ER vesicles, cytosol, and nuclear interior; thus demonstrating that the FGFR1 TM does not function as a NLS. To test whether cytosolic FGFR1 provides a source of nuclear FGFR1, cells were transfected with FGFR1(SP−) (SP was deleted), resulting in cytosolic, non‐membrane, protein accumulation in the cytosol and the cell nucleus. Our results indicate that an unstable association with cellular membranes is responsible for the release of FGFR1 into the cytosol and cytosolic FGFR1 constitutes the source of the nuclear receptor. J. Cell. Biochem. 88: 1273–1291, 2003. © 2003 Wiley‐Liss, Inc.
Le consulting et l'Etat : une analyse comparée de l'offre et de la demande

This article examines the growing importance of management consultants in state reform from the point of view of supply and demand. Although they vary from one country to another, the size of the state, the openness of the consulting system in matters of policy-making, and the reforms inspired by New Public Management, have all contributed to the increase in demand for consulting services within public administration. On the supply side, the author examines three factors : the development of the consulting industry, the marketing strategies used by consultants to promote their products, and finally the efforts at representation made by consultants to build networks of contacts with government decision-makers. If consultants have contributed to the “privatisation” of government, it is paradoxical to note that their more or less intimate relationship with the government has turned them into less “private” and more “public” actors than they were previously.
Phase I/II trial of dexverapamil, epirubicin, and granulocyte‐macrophage–colony stimulating factor in patients with advanced pancreatic adenocarcinoma

Background. The purpose of this study was to determine the maximum tolerated dose (MTD) of a cytotoxic regimen consisting of the second‐generation chemosensitizer dexverapamil (DVPM), high dose epirubicin, and recombinant human granulocyte‐macrophage‐colony stimulating factor (GM‐CSF) in pancreatic carcinoma.
Chemical constituents and biological activities of the genus Linaria (Scrophulariaceae)

This is a review on 95 references dealing with the genus Linaria (Scrophularioideae-Antirrhineae tribe), a known genus of the Scrophulariaceae family, which comprises about 200 species mainly distributed in Europe, Asia and North Africa. The use of some Linaria species in folk medicine has attracted the attention for chemical and biological studies. This report is aimed to be a comprehensive overview on the isolated or identified known and often new metabolites from the 41 Linaria species so far cited. It is organised presenting first the phytochemical classes of alkaloids, polyphenols including flavonoids, the latter being quite diffused and mostly present as flavones, flavonols and their glycosides, and terpenoids including iridoids and steroids. Second, the results from biological investigation on plant extracts, pure natural products isolated from Linaria species and some synthetic derivatives are reported, with antitumour, anti-acetylcholinesterase, anti-inflammatory and analgesic, antioxidant and antibacterial activities.
The Role of Defensins in HIV Pathogenesis

Profound loss of CD4+ T cells, progressive impairment of the immune system, inflammation, and sustained immune activation are the characteristics of human immunodeficiency virus-1 (HIV-1) infection. Innate immune responses respond immediately from the day of HIV infection, and a thorough understanding of the interaction between several innate immune cells and HIV-1 is essential to determine to what extent those cells play a crucial role in controlling HIV-1 in vivo. Defensins, divided into the three subfamilies α-, β-, and θ-defensins based on structure and disulfide linkages, comprise a critical component of the innate immune response and exhibit anti-HIV-1 activities and immunomodulatory capabilities. In humans, only α- and β-defensins are expressed in various tissues and have broad impacts on HIV-1 transmission, replication, and disease progression. θ-defensins have been identified as functional peptides in Old World monkeys, but not in humans. Instead, θ-defensins exist only as pseudogenes in humans, chimpanzees, and gorillas. The use of the synthetic θ-defensin peptide “retrocyclin” as an antiviral therapy was shown to be promising, and further research into the development of defensin-based HIV-1 therapeutics is needed. This review focuses on the role of defensins in HIV-1 pathogenesis and highlights future research efforts that warrant investigation.
Switch from Calcineurin Inhibitors to Sirolimus-Induced Renal Recovery in Heart Transplant Recipients in the Midterm Follow-up

Background. Calcineurin inhibitor (CI)-based immunosuppression has prolonged the survival of heart transplant recipients. However, CI-induced renal injury remains as a major problem in these patients. Sirolimus is an immunosuppressant with no significant impact on renal function. A limited number of recent papers have showed that the switch from CI to sirolimus improved renal function in late follow-up of heart transplant patients with CI-related nephrotoxicity. Methods. Ten heart transplant recipients with CI-induced nephrotoxicity (creatinine 3.9±1.8 mg/dl) at a median of 701 (465 to 1325) days posttransplant had CI switched to sirolimus (target though levels 10 to 14 ng/ml) while mycophenolate mofetil (MMF, 3g/day) was maintained and adjusted according to white blood cell count. Results. This maneuver caused a marked decrease in serum creatinine (P<0.00001) at 30 (1.2±0.4 mg/dl), 90 (1.3±0.4 mg/dl) and 180 (1.3±0.4 mg/dl) days postconversion and a significant decrease in serum potassium levels (5.1±0.5 at baseline vs. 3.9±0.3 at 180 days, P<0.00005). After the drugs switch no changes in hemoglobin levels, white blood cell count, platelets count, blood glucose and glutamic oxaloacetic transaminase plasma levels were observed. Total cholesterol increased from 242±28 to 290±117 mg/dl (P>0.05) after 90 days and decreased to 216±58 mg/dl at day 180 (P>0.05) after statins dose adjustment. Rejection and infection rates were not modified by sirolimus. Conclusions. Conversion to a sirolimus-based immunosuppression regimen associated with MMF allowed striking renal function recovery in heart transplant recipients with calcineurin inhibitor-induced renal impairment at midterm follow-up.
Pancreatic reg gene expression is inhibited during cellular differentiation.

BACKGROUND AND OBJECTIVE Factors that control pancreatic regenerating (reg I) gene expression are unknown, but it is believed that its expression may correspond with cellular differentiation. The authors recently demonstrated that reg I is expressed in AR42J, a rat acinar cell line whose state of differentiation can be modulated by dexamethasone. They used this line to study reg I expression during cellular proliferation and differentiation. METHODS After treatment of cells with 10 nmol/L dexamethasone, proliferation was assayed by thymidine incorporation; differentiation by expression of elastase I mRNA. Reg I mRNA levels were measured using a rat reg I cDNA probe, and reg I protein levels assayed by enzyme-linked immunosorbent assay of cellular lysates with a polyclonal antibody. The effect of gastrin, cholecystokinin and glucagon on reg I expression was also studied. RESULTS When compared with controls, treatment with dexamethasone caused thymidine incorporation to decrease and elastase mRNA levels to increase. Reg I mRNA decreased from controls of 100 +/- 16% to 40 +/- 18% (p < 0.05), and reg I protein levels decreased as well. Gastrointestinal hormones had no significant effect on either elastase or reg I gene expression. CONCLUSIONS Expression of reg I inversely correlates with the level of cellular differentiation, can be modulated via the glucocorticoid receptor, and is a potential marker of gastrointestinal epithelial differentiation. Despite its presence within a pancreatic acinar cell line, reg I gene expression is not modulated by gastrointestinal hormones.
Vascular adaptations to 8‐week cycling training in older men

Aim: Because age‐related changes in the large conduit arteries (increased wall thickness, and attenuated arterial compliance and endothelial function) are associated with cardiovascular pathology, prevention is of paramount importance. The effects of endurance training (i.e. walking or cycling) in older humans are assessed in cross‐sectional studies, examining the brachial and carotid arteries (supplying non‐trained areas). The purpose of this study was to assess the effects of 8‐week endurance training in older men on conduit artery characteristics in the trained and non‐trained vascular beds.