Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98.

PURPOSE We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. PATIENTS AND METHODS Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). RESULTS At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P < .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. CONCLUSION An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.
Smoke-Free Men: Competing and Connecting to Quit

Purpose: The purpose of this study was to explore gender-related factors that motivate and support men’s smoking reduction and cessation to inform effective men-centered interventions. Approach or Design: Focus group design using a semi-structured interview guide. Setting: Three communities in British Columbia, Canada. Participants: A total of 56 men who currently smoked and were interested in reducing or quitting or had quit. Intervention: N/A. Methods: Data collected in 6 focus group discussions were transcribed and analyzed in accord with principles of thematic qualitative methods. Results: We report the results across 4 interconnected themes: (1) the fight to quit takes several rounds, (2) the motivation of supportive competition, (3) challenges and benefits of connecting with smoke-free peers, and (4) playing up the physical and financial gains. Conclusions: Masculine-based perspectives positioned quitting alongside fighting for self-control, competing, connecting, physical prowess, and having extra cash as motivating components of programs to engage men in efforts to be smoke-free. It may be worthwhile to consider the inclusion of gain-framed and benefit-focused messaging in programs that support men’s tobacco cessation.
Parkinson's disease and its comorbid disorders

Using data from death certificates, we compared underlying causes of death for two populations of Michigan decedents: (1) persons 40 years of age and older for whom Parkinson's disease (PD) was listed as a contributing cause of death and who died in the years 1970 through 1989, and (2) all persons in Michigan over 40 years of age who died in 1970, 1980, or 1990. PD decedents were approximately 1.5 times more likely to die from cerebrovascular disease and three to four times more likely to die from pneumonia/influenza, but they had just 29% of the expected number of deaths due to cancer. These associations were maintained irrespective of gender or race. PD decedents had diabetes melli-tus and heart diseases as frequently as decedents in the general population, but liver diseases were less frequent among PD decedents. These trends held throughout the 21-year study period. When we stratified cancers by whether they are known to be (1) highly related, (2) moderately related, or (3) weakly related or unrelated to smoking, there were still 2.5 times fewer cancers unrelated or weakly related to smoking among PD decedents than among decedents in the general population. We believe that the greater frequency of cerebrovascular disease in PD decedents may be due to a detection bias, since PD patients are more likely to be seen by neurologists, who are more apt to diagnose and document diseases of the nervous system. Pneumonia/influenza is more common among PD patients because of their relative immobility near the end of life. Although the inverse association of PD with cancer remains unexplained, there may be genetic or environmental factors that individuals with PD have been exposed to that decrease their susceptibility to cancer.
Mecanismos externos de control de la empresa: el papel de los bancos y el mercado de control en entornos de baja protección del inversor

Los mecanismos de gobierno de la empresa facilitan la creacion de valor en presencia de asimetrias de informacion y conflictos de agencia. Sin embargo diferentes factores afectan al diseno y a la eficiencia de estos mecanismos. En particular su utilizacion esta condicionada por el marco legal e institucional de proteccion de los derechos de los accionistas, por las diferencias entre los niveles de concentracion de la propiedad y por la eficiencia y desarrollo de los mercados. Estas diferencias institucionales en el sistema de gobierno afectan a las relaciones entre los accionistas, a la eficiencia del Consejo de Administracion y a la utilizacion del mercado de control para supervisar e incentivar las actuaciones de los directivos
A framework for fault diagnosis of hybrid systems based on predicate abstractions

In this paper we aim at checking fault reconfigurability in hybrid systems. A hybrid system is a system mixing continuous and discrete behaviours that cannot be faithfully modeled neither by using a formalism with continuous dynamics only nor by a formalism including only discrete dynamics. We extend the well known framework of hybrid automata for modeling hybrid systems, adding faults leading to recoverable and unrecoverable states. We use a discrete abstraction of hybrid automata to design a diagnoser that observes the external behaviour of the system and announces whether a fault has occurred or not. Moreover if the diagnoser is able to detect the fault before the system reaches an unrecoverable state, then the automaton is also reconfigurable. We prove the effectiveness of this procedure with a simple case study.
Differential Expression of Antioxidant Enzymes During Degradation of Azo Dye Reactive black 8 in Hairy roots of Physalis minima L.

The enzymes involved in the protection of plant metabolism in presence of azo dye was characterized by studying activities of the role of antioxidant enzymes in the hairy roots (HRs) of Physalis minima L. during degradation of an azo dye, Reactive Black 8 (RB8). When the HRs were exposed to RB8 (30 mg L−1), a nine fold increase in SOD activity was observed after 24 h, while 22 and 50 fold increase in activity was observed for POX and APX respectively after 72 h, whereas there was no significant change in activity of CAT. The activation of different antioxidant enzymes at different time intervals under dye stress suggests the synchronized functioning of antioxidant machinery to protect the HRs from oxidative damage. FTIR analysis confirmed the degradation of dye and the non-toxic nature of metabolites formed after dye degradation was confirmed by phytotoxicity study.
An Improved Relay Selection Scheme with Hybrid Relaying Protocols

In this paper, we propose an improved relay selection scheme based on a hybrid relaying protocol (RS-HRP). In the proposed scheme, all the relays are included into two groups, referred to as an amplify and forward (AAF) and a decode and forward (DAF) relay groups. The relays which decode successfully are included in the DAF group and the rest of relays, which fail to decode correctly, are included in the AAF group. The best relay, which maximizes the destination SNR, will be selected from all relays in both AAF and DAF relay groups. If it is selected from the AAF group, it will amplify the received signal while if it is selected from the DAF group, it will decode the received signals and re-encode. Results show that the proposed relay selection scheme significantly outperforms the conventional AAF selection scheme and this performance gain considerably grows as the number of relays increases. It also approaches the perfect DAF relay selection as the SNR increases.
Induction of Neuronal Apoptosis by Thiol Oxidation

Abstract: The membrane‐permeant oxidizing agent 2,2′‐dithiodipyridine (DTDP) can induce Zn2+ release from metalloproteins in cell‐free systems. Here, we report that brief exposure to DTDP triggers apoptotic cell death in cultured neurons, detected by the presence of both DNA laddering and asymmetric chromatin formation. Neuronal death was blocked by increased extracellular potassium levels, by tetraethylammonium, and by the broad‐spectrum cysteine protease inhibitor butoxy‐carbonyl‐aspartate‐fluoromethylketone. N,N,N′,N′‐Tetrakis‐(2‐pyridylmethyl)ethylenediamine (TPEN) and other cell‐permeant metal chelators also effectively blocked DTDP‐induced toxicity in neurons. Cell death, however, was not abolished by the NMDA receptor blocker MK‐801, by the intracellular calcium release antagonist dantrolene, or by high concentrations of ryanodine. DTDP generated increases in fluorescence signals in cultured neurons loaded with the zinc‐selective dye Newport Green. The fluorescence signals following DTDP treatment also increased in fura‐2‐ and magfura‐2‐loaded neurons. These responses were completely reversed by TPEN, consistent with a DTDP‐mediated increase in intracellular free Zn2+ concentrations. Our studies suggest that under conditions of oxidative stress, Zn2+ released from intracellular stores may contribute to the initiation of neuronal apoptosis.
Sociocultural differences in gait

Transcultural differences in routine motor behavior and movement disorders have rarely been assessed. In the present study gait was studied in 47 healthy inhabitants of Tyrol living in rural or semi‐urban (Innsbruck, Austria) settings and 43 healthy subjects residing in Berlin, Germany. In addition, gait was assessed in 23 patients in early stages of idiopathic Parkinson's disease (11 in Berlin, 12 in Innsbruck). Healthy subjects in Berlin showed faster gait velocity than their counterparts in Tyrol, and patients with Parkinson's disease were slightly slower than their respective healthy peers in both environments. Surprisingly, patients with Parkinson's disease from Berlin had significantly faster walking speeds than both patients and healthy control subjects from Tyrol. High gait tempo in parkinsonian patients from Berlin was characterized by fast step‐rates and short strides. Differences in normal gait in different sociocultural settings are thus reflected in parkinsonian slowing of gait.
TGF-β Regulates miR-206 and miR-29 to Control Myogenic Differentiation through Regulation of HDAC4

MicroRNAs (miRs) are emerging as prominent players in the regulation of many biological processes, including myogenic commitment and skeletal muscle formation. Members of the TGF-β family can influence the proliferation and myogenic differentiation of cells, although it is presently not clear what role miRNAs play in the TGF-β-mediated control of myogenic differentiation. Here, we demonstrate in the myogenic C2C12 cell line, and in primary muscle cells, that miR-206 and miR-29-two miRs that act on transcriptional events implicated in muscle differentiation are down-regulated by TGF-β. We further demonstrate that TGF-β treatment of myogenic cells is associated with increased expression of histone deacetylase 4 (HDAC4), a key inhibitor of muscle differentiation that has been identified as a target for regulation by miR-206 and miR-29. We confirmed that increased expression of miR-206 and miR-29 resulted in the translational repression of HDAC4 in the presence or absence of TGF-β via interaction with the HDAC4 3′-untranslated region. Importantly, we found that miR-206 and miR-29 can attenuate the inhibitory actions of TGF-β on myogenic differentiation. Furthermore, we present evidence that the mechanism by which miR-206 and miR-29 can inhibit the TGF-β-mediated up-regulation of HDAC4 is via the inhibition of Smad3 expression, a transducer of TGF-β signaling. These findings identify a novel mechanism of interaction between TGF-β and miR-206 and -29 in the regulation of myogenic differentiation through HDAC4.
Effects of Maternal Dexamethasone Therapy on Fetal Lung Development in the Rhesus Monkey

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.
Modifiers of terminal deficiency-associated position effect variegation in Drosophila.

Terminal deletions of a Drosophila minichromosome (Dp(1;f)1187) dramatically increase the position effect variegation (PEV) of a yellow(+) body-color gene located in cis. Such terminal deficiency-associated PEV (TDA-PEV) can be suppressed by the presence of a second minichromosome, a phenomenon termed "trans-suppression. " We performed a screen for mutations that modify TDA-PEV and trans-suppression. Seventy suppressors and enhancers of TDA-PEV were identified, but no modifiers of trans-suppression were recovered. Secondary analyses of the effects of these mutations on different PEV types identified 10 mutations that modify only TDA-PEV and 6 mutations that modify TDA-PEV and only one other type of PEV. One mutation, a new allele of Su(var)3-9, affects all forms of PEV, including silencing associated with the insertion of a transgene into telomeric regions (TPE). This Su(var)3-9 allele is the first modifier of PEV to affect TPE and provides a unique link between different types of gene silencing in Drosophila. The remaining mutations affected multiple PEV types, indicating that general PEV modifiers impact TDA-PEV. Modifiers of TDA-PEV may identify proteins that play important roles in general heterochromatin biology, including proteins involved in telomere structure and function and the organization of chromosomes in the interphase nucleus.
Controlled liver splitting for transplantation in two recipients: Technique, results and perspectives

A technique of controlled liver splitting for transplantation in two recipients is proposed, based on a full anatomical assessment of the graft including arteriography and cholangiography on the back‐table. Using eight livers, 16 patients received a graft: right liver (eight patients), left lobe (four) or left liver (four). Twelve patients required urgent or very urgent transplantation. Anatomical assessment of the graft demonstrated a portal bifurcation in all cases, a common trunk of the left and middle hepatic veins in five, a right biliary duplication in three and duplication of the left branch of the middle hepatic artery in one. After revascularization of the graft, bleeding was greater in patients with a right graft, particularly if the middle hepatic vein had been ligated. The main postoperative complications were hepatic artery thrombosis (four cases), biliary complications (four), portal vein thrombosis (two), haematoma (two) and abscess (two). No primary non‐function of the graft was observed. The postoperative survival rate was 75 per cent. The four patients in whom transplantation was not considered urgent are still alive. The immediate survival rate of the grafts was 69 per cent. These results compare favourably with those in the literature. In spite of the technical, logistical and ethical problems raised by this technique, the results suggest that controlled liver splitting for transplantation in two recipients may in the future significantly improve the feasibility of liver transplantation.
Malignant lymphoma in primary Sjögren's syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjögren's Syndrome.

OBJECTIVE Several reports have noted an increased incidence of malignant lymphoma in patients with Sjögren's syndrome (SS). Each case series has consisted of a limited number of patients with malignant non-Hodgkin's lymphoma (MNHL). In this report, we describe the disease characteristics, the clinical course, and the evolution in 33 patients followed up in 9 European medical centers. METHODS The pool of MNHL patients from participating centers in a European Concerted Action on SS were analyzed. We report on the disease characteristics, its evolution, prognosis, current treatment practices, and survival. RESULTS The MNHLs in this study were primarily situated in the marginal zone (48.5%), with the manifestations mostly extranodal (78.8%) and most often identified in the salivary glands (54.6%). Lymphadenopathy (65.6%), skin vasculitis (33.3%), peripheral nerve involvement (24.2%), low-grade fever (25.0%), anemia (48.1%), and lymphopenia (78.6%) were observed significantly more frequently than in the general SS population. Patients with high-to-intermediate grade lymphoma had significantly worse survival (P = 0.041). The presence of B symptoms (fever, night sweats, and weight loss) and a large tumor diameter (>7 cm) were additional independent risk factors for death. CONCLUSION The novel observations of this study were those related to the type of MNHL, the survival prognosis, and the very high frequency of skin vasculitis, peripheral nerve involvement, anemia, and lymphopenia. Some of the previously reported results on extranodal manifestations were confirmed.
CALL FOR PAPERS Bioengineering the Lung: Molecules, Materials, Matrix, Morphology, and Mechanics Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis

functional between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis. Hox genes encode transcription factors governing complex developmental processes in several organs. A subset of Hox genes are expressed in the developing lung. Except for Hoxa5 , the lack of overt lung phenotype in single mutants suggests that Hox genes may not play a predominant role in lung ontogeny or that functional redundancy may mask anomalies. In the Hox5 paralog group, both Hoxa5 and Hoxb5 genes are expressed in the lung mesenchyme whereas Hoxa5 is also expressed in the tracheal mesenchyme. Herein, we generated Hoxa5 ; Hoxb5 compound mutant mice to evaluate the relative contribution of each gene to lung development. Hoxa5 ; Hoxb5 mutants carrying the four mutated alleles displayed an aggravated lung phenotype, resulting in the death of the mutant pups at birth. Characterization of the phenotype highlighted the role of Hoxb5 in lung formation, the latter being involved in branching morphogenesis, goblet cell speciﬁcation, and postnatal air space structure, revealing partial functional redundancy with Hoxa5 . However, the Hoxb5 lung phenotypes were less severe than those seen in Hoxa5 mutants, likely because of Hoxa5 compensation. New speciﬁc roles for Hoxa5 were also unveiled, demonstrating the extensive contribution of Hoxa5 to the developing respiratory system. The exclusive expression of Hoxa5 in the trachea and the phrenic motor column likely underlies the Hoxa5 -speciﬁc trachea and diaphragm phenotypes. Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog genes shared some functions during lung morphogenesis, Hoxa5 playing a predominant role. In situ hybridization analyses. Radioactive in situ hybridization experiments were performed on frontal sections of E13.5 embryos as described (28). The following murine sequences were used as speciﬁc templates for synthesizing [ 35 S]UTP-labeled riboprobes: a 850-bp Bgl II- Hind III genomic fragment containing the 3 = -untranslated region of Hoxa5 exon 2 (11), a 430-bp Bam HI- Hind III cDNA fragment covering part of Hoxb5 exon 1 (31), and a 200-bp Eco RI- Xba I genomic fragment corresponding to Hoxc5 exon 2 (18). After expo-sure, slides were counterstained with toluidine blue. Experiments were performed on two to ﬁve specimens per genotype tested. a triplicate. to for each genotype
The ecology of avian influenza viruses in wild dabbling ducks (Anas spp.) in Canada

Avian influenza virus (AIV) occurrence and transmission remain important wildlife and human health issues in much of the world, including in North America. Through Canada’s Inter-Agency Wild Bird Influenza Survey, close to 20,000 apparently healthy, wild dabbling ducks (of seven species) were tested for AIV between 2005 and 2011. We used these data to identify and evaluate ecological and demographic correlates of infection with low pathogenic AIVs in wild dabbling ducks (Anas spp.) across Canada. Generalized linear mixed effects model analyses revealed that risk of AIV infection was higher in hatch-year birds compared to adults, and was positively associated with a high proportion of hatch-year birds in the population. Males were more likely to be infected than females in British Columbia and in Eastern Provinces of Canada, but more complex relationships among age and sex cohorts were found in the Prairie Provinces. A species effect was apparent in Eastern Canada and British Columbia, where teal (A. discors and/or A. carolinensis) were less likely to be infected than mallards (A. platyrhynchos). Risk of AIV infection increased with the density of the breeding population, in both Eastern Canada and the Prairie Provinces, and lower temperatures preceding sampling were associated with a higher probability of AIV infection in Eastern Canada. Our results provide new insights into the ecological and demographic factors associated with AIV infection in waterfowl.