Miracle-dz/UniFAR-FTUs huggingface dataset:
Future Time Perspective and End-of-Life Planning in Older Adults

This study explores the extent to which cognitive processes, specifically perceptions of one’s distance to death, are associated with informal and formal advance care planning (ACP) in a sample of older adults. Data come from the New Jersey End-of-Life (EOL) study, a survey of 305 adults aged 55–91. Binary logistic regression models evaluate the odds that someone conducted ACP. Persons who perceive remaining life span to be expansive or limited have significantly lower odds of formally planning for the EOL, relative to those in the middle category. Death anxiety and having a family confidante partially explain these associations. The association between future time perspective (FTP) and discussions is not statistically significant. Practitioners may consider individuals’ FTPs when discussing preferences for EOL medical care.
Quantification of Vertebral Involvement in Metastatic Spinal Disease

Introduction: For patients with a solitary and well-delimitated spinal metastasis that resides inside the vertebral body, without vertebral canal invasion, and who are in good general health with a long life expectancy, en bloc spondylectomy/total vertebrectomy combined with the use of primary stabilizing instrumentation has been advocated. However, clinical experience suggests that these qualifying conditions occur very rarely. Objective: The purpose of this paper is to quantify the distribution of vertebral involvement in spinal metastases and determine the frequency with which patients can be considered candidates for radical surgery (en bloc spondylectomy). Methods: Consecutive patients were classified accordingly to Enneking’s and Tomita’s schemes for grading vertebral involvement of metastases. Results: Fifty-one (51) consecutive patients were evaluated. Eighty-three percent of patients presented with the involvement of multiple vertebral levels and/or spinal canal invasion. Conclusion: Because of diffuse vertebral involvement of metastases, no patients in this sample were considered to be candidates for radical spondylectomy of vertebral metastasis.
Trial watch

Tumor-targeting immune responses provide a significant contribution to (when they do not entirely account for) the clinical activity of diverse antineoplastic regimens, encompassing not only a large panel of immunotherapeutic strategies but also conventional cytotoxic molecules, targeted anticancer agents and irradiation. In line with this notion, several approaches have been devised to elicit novel or boost existing anticancer immune responses, including the administration of immunomodulatory cytokines. Such a relatively unspecific intervention suffices to mediate clinical effects in (at least a subset of) patients bearing particularly immunogenic tumors, like melanoma and renal cell carcinoma. More often, however, immunostimulatory cytokines are administered to boost the immunogenic potential of other agents, including (but not limited to) immune checkpoint-blocking antibodies, anticancer vaccines, oncolytic viruses and immunogenic chemotherapeutics. Here, we summarize the latest advances in the clinical development of recombinant cytokines as an immunomodulatory intervention for cancer therapy.
Prospective Safety Surveillance of GH-Deficient Adults: Comparison of GH-Treated vs Untreated Patients

Context: In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown. Objective: The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement. Design and Setting: This was a prospective observational study in the setting of US clinical practices. Patients and Outcome Measures: AEs were compared between GH-treated (n = 1988) and untreated (n = 442) GH-deficient adults after adjusting for baseline group differences and controlling the false discovery rate. The standardized mortality ratio was calculated using US mortality rates. Results: After a mean follow-up of 2.3 years, there was no significant difference in rates of death, cancer, intracranial tumor growth or recurrence, diabetes, or cardiovascular events in GH-treated compared with untreated patients. The standardized mortality ratio was not increased in either group. Unexpected AEs (GH-treated vs untreated, P ≤ .05) included insomnia (6.4% vs 2.7%), dyspnea (4.2% vs 2.0%), anxiety (3.4% vs 0.9%), sleep apnea (3.3% vs 0.9%), and decreased libido (2.1% vs 0.2%). Some of these AEs were related to baseline risk factors (including obesity and cardiopulmonary disease), higher GH dose, or concomitant GH side effects. Conclusions: In GH-deficient adults, there was no evidence for a GH treatment effect on death, cancer, intracranial tumor recurrence, diabetes, or cardiovascular events, although the follow-up period was of insufficient duration to be conclusive for these long-term events. The identification of unexpected GH-related AEs reinforces the fact that patient selection and GH dose titration are important to ensure safety of adult GH replacement.
Myocyte Enhancer Factor 2A and 2D Undergo Phosphorylation and Caspase-Mediated Degradation during Apoptosis of Rat Cerebellar Granule Neurons

Myocyte enhancer factor 2 (MEF2) proteins are important regulators of gene expression during the development of skeletal, cardiac, and smooth muscle. MEF2 proteins are also present in brain and recently have been implicated in neuronal survival and differentiation. In this study we examined the cellular mechanisms regulating the activity of MEF2s during apoptosis of cultured cerebellar granule neurons, an established in vitromodel for studying depolarization-dependent neuronal survival. All four MEF2 isoforms (A, B, C, and D) were detected by immunoblot analysis in cerebellar granule neurons. Endogenous MEF2A and MEF2D, but not MEF2B or MEF2C, were phosphorylated with the induction of apoptosis. The putative sites that were phosphorylated during apoptosis are functionally distinct from those previously reported to enhance MEF2 transcription. The increased phosphorylation of MEF2A and MEF2D was followed by decreased DNA binding, reduced transcriptional activity, and caspase-dependent cleavage to fragments containing N-terminal DNA binding domains and C-terminal transactivation domains. Expression of the highly homologous N terminus of MEF2A (1–131 amino acids) antagonized the transcriptional activity and prosurvival effects of a constitutively active mutant of MEF2D (MEF2D-VP16). We conclude that MEF2A and MEF2D are prosurvival factors with high transcriptional activity in postmitotic cerebellar granule neurons. When these neurons are induced to undergo apoptosis by lowering extracellular potassium, MEF2A and MEF2D are phosphorylated, followed by decreased DNA binding and cleavage by a caspase-sensitive pathway to N-terminal fragments lacking the transactivation domains. The degradation of MEF2D and MEF2A and the generation of MEF2 fragments that have the potential to act as dominant-inactive transcription factors lead to apoptotic cell death.
The influence of diet on the assimilation efficiency of 47 polychlorinated biphenyl congeners in Japanese koi (Cyprinus carpio)

The influence of diet on polychlorinated biphenyl (PCB) assimilation was investigated by measuring dietary assimilation efficiencies (AEs) for 47 PCB congeners in juvenile koi (Cyprinus carpio) fed five experimental diets. Two of the diets were naturally contaminated and were obtained by collecting mayflies from Lake Erie (ON, Canada) and emerald shiners from the Detroit River (MI, USA). The remaining diets consisted of commercial fish pellets (lipid contents from 6.7 to 24%) that were contaminated by spiking with a PCB mixture. Experimental fish were held individually to quantify the amount of food consumed per fish and, following a 48‐h fasting period to facilitate food digestion and assimilation; AEs were determined by mass balance. Fish fed the benthic invertebrate food exhibited the highest PCB AEs (70–101%) and were significantly elevated compared to the other diet treatments (AEs ranging from 23 to 87%). The PCB AEs for fish fed emerald shiners did not differ from those fed pellet formulations. Variation among PCB AEs was not related to diet lipid content. For all diet treatments, PCB AEs were significantly related to chemical hydrophobicity. The relationship between chemical AE and n‐octanol/water partition coefficient (KOW) was best explained by a linear model compared to a two‐phase resistance model. Overall, PCB AEs were observed to be dependent on both diet type and chemical hydrophobicity, with both factors contributing nearly equally to the variation measured in this toxicokinetic parameter. Environ. Toxicol. Chem. 2010;29:401–409. © 2009 SETAC
Improving Hospital Discharge Time

AbstractDelays in discharging patients can impact hospital and emergency department (ED) throughput. The discharge process is complex and involves setting specific challenges that limit generalizability of solutions.The aim of this study was to assess the effectiveness of using Six Sigma methods to improve the patient discharge process.This is a quantitative pre and post-intervention study.Three hundred and eighty-six bed tertiary care hospital.A series of Six Sigma driven interventions over a 10-month period.The primary outcome was discharge time (time from discharge order to patient leaving the room). Secondary outcome measures included percent of patients whose discharge order was written before noon, percent of patients leaving the room by noon, hospital length of stay (LOS), and LOS of admitted ED patients.Discharge time decreased by 22.7% from 2.2 hours during the preintervention period to 1.7 hours post-intervention (P < 0.001). A greater proportion of patients left their room before noon in the postintervention period (P < 0.001), though there was no statistical difference in before noon discharge. Hospital LOS dropped from 3.4 to 3.1 days postintervention (P < 0.001). ED mean LOS of patients admitted to the hospital was significantly lower in the postintervention period (6.9 ± 7.8 vs 5.9 ± 7.7 hours; P < 0.001). Six Sigma methodology can be an effective change management tool to improve discharge time. The focus of institutions aspiring to tackle delays in the discharge process should be on adopting the core principles of Six Sigma rather than specific interventions that may be institution-specific.
Acute stress-induced (takotsubo) cardiomyopathy

Acute stress-induced (takotsubo) cardiomyopathy has a dramatic clinical presentation, mimicking an acute myocardial infarction and is triggered by intense emotional or physical stress. In this paper, we review the current state of knowledge of the mechanistic physiology underlying the left ventricular ballooning. The pathophysiology of the recovery from this acute heart failure syndrome is presented. The short-term and long-term outlook puts this new syndrome on a different perspective compared with recently held views. Current knowledge on susceptibility and predisposition already define distinctive characteristics of patients with takotsubo compared with myocardial infarction. Gaps in knowledge and future directions of research are identified in order to best direct efforts for identifying specific therapies for this condition, in the acute setting, to mitigate postacute symptoms or to prevent recurrences, none of which exist.
Dijon’s vanishing lead with regard to low incidence of stroke

Background: Towards the end of the 20th century, the city of Dijon, France, had a lower incidence of stroke than that found in other studies. It was hypothesized that genetic and environmental factors were responsible for this so‐called French paradox. We aim to evaluate recent changes in stroke incidence to determine whether or not the Dijon exception still exists.
Environmentally Benign Fouling-Resistant Marine Coatings: A Review

ABSTRACT The undesirable accumulation of marine organisms on any surfaces immersed in seawater is termed as marine fouling. This natural phenomenon contributes a major economic concern for marine industries, e.g. for ships, vessels, oil, wind-turbine sea-platforms, pipelines, water valves and filters by limiting the performances of the devices and materials. In the last decades, several efforts have been employed in the development of efficient antifouling (AF) coatings by following the recent trend in materials science. The current review presents the research and development made in AF strategies for coatings based on two main approaches, detachment of biofoulants or preventing biofoulants attachment. Graphical Abstract GRAPHICAL ABSTRACT
Chemical inhibitors of CYP450 enzymes in liver microsomes: combining selectivity and unbound fractions to guide selection of appropriate concentration in phenotyping assays

Abstract 1. Chemical inhibition is the widely used method in reaction phenotyping assays for estimation of specific enzyme contribution to a given metabolic pathway. The results from phenotyping assays depend on the selectivity of chemical inhibitor and the concentration of inhibitor used in the incubation. 2. The higher protein concentrations used in the in vitro phenotyping assays will impact the inhibitory potency of chemical inhibitors. The objective of the study is to evaluate comprehensively the selectivity of chemical inhibitors and to guide in selecting appropriate concentration of the chemical inhibitors to be used in the phenotyping assays based on unbound fractions. 3. Selectivity of chemical inhibitors against nine major CYP450 isoforms was determined in liver microsomes using standard probe substrates. The unbound fractions of the selective inhibitors were determined in human liver microsomes using high-throughput equilibrium dialysis. Combining unbound inhibitor concentrations that are required to inhibit the CYP450 activities by 90% and unbound fractions of the chemical inhibitors in liver microsomes appropriate total concentrations of the inhibitors to be used in the phenotyping assays were reported. 4. The findings suggest that non-specific binding of the chemical inhibitors need to be taken into account while selecting concentrations for phenotyping assays.
Matching Language and Hardware for Parallel Computation in the Linda Machine

The Linda Machine is a parallel computer that has been designed to support the Linda parallel programming environment in hardware. Programs in Linda communicate through a logically shared associative memory called tuple space. The goal of the Linda Machine project is to implement Linda's high-level shared-memory abstraction efficiently on a nonshared-memory architecture. The authors describe the machine's special-purpose communication network and its associated protocols, the design of the Linda coprocessor, and the way its interaction with the network supports global access to tuple space. The Linda Machine is in the process of fabrication. The authors discuss the machine's projected performance and compare this to software versions of Linda. >
Manufacturing and Characterization of Twin‐Roll Cast Aluminum‐Steel Clad Strips

The manufacturing of clad strips by means of twin‐roll casting is a prospective trend regarding the production of lightweight materials. This study is dedicated to an analysis of bond formation conditions during the twin‐roll casting of clad strips of aluminum EN AW‐1070 and an austenitic stainless steel 1.4301. The procedures of steel substrate preparation and their influence on the diffusion bond are investigated. These include surface pre‐treatment of the steel substrate by means of mechanical grinding and laser irradiation as well as its pre‐heating. Using the different sets of process parameters, the clad strips with a thickness of 2.5 mm are manufactured and characterized. Light and electron microscopy are used to characterize the microstructure of the aluminum layer and the bond zone and to investigate the mechanism of bond formation. The evaluation of the strips’ properties is carried out by means of adhesive tensile tests, peeling tests, uniaxial tensile tests, and fatigue tests. The influence of each of the substrate preparation methods as well as post heat treatment on the parameters of bond zone and the mechanical properties of the clad strip is investigated. The implementation of the investigated manufacturing method allows producing thin clad strips with excellent characteristics.
Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation

The safety, efficacy, and effect on immunosuppression levels of telaprevir (TVR) or boceprevir (BOC) in combination with peginterferon (PEG‐IFN) and ribavirin (RBV) in recipients of liver transplantation (LT) with hepatitis C virus (HCV) genotype 1 have not been defined. We report our 3 centers' preliminary experiences with administering triple antiviral treatment protocols containing PEG‐IFN, RBV, and TVR or BOC. Patients with biopsy‐proven HCV recurrence (METAVIR grade ≥ 3 and/or stage ≥ 2) received TVR with PEG‐IFN/RBV for 12 weeks and then PEG‐IFN/RBV for 36 weeks or BOC with PEG‐IFN/RBV for 44 weeks after 4 weeks of lead‐in PEG‐IFN/RBV. Maintenance immunosuppression was changed to cyclosporine whenever possible, and the levels were followed closely. PEG‐IFN/RBV dose adjustments were based on patients' tolerance. Sixty patients started triple antiviral treatment, and they were followed for up to 66 weeks (mean = 35 weeks); all were followed at least 12 weeks. Thirty of the 35 patients treated with TVR (86%) achieved undetectable HCV RNA levels after an average of 6 weeks, whereas 12 patients (48%) in the BOC‐treated group achieved undetectable HCV RNA levels after a mean of 11 weeks. According to an intention‐to‐treat analysis, 14 of 21 TVR‐treated patients (67%) and 10 of 22 patients who received BOC (45%) achieved undetectable HCV RNA levels at week 24 without viral breakthrough at the last follow‐up. Cytopenias complicated both regimens; all patients required dose reductions of PEG‐IFN and/or RBV or the administration of hematological growth factors. One death occurred in each group on triple antiviral treatment. In conclusion, TVR or BOC combined with PEG‐IFN/RBV achieved on‐treatment virological response rates of approximately 50% to 60% in patients with recurrent HCV after LT, but significant side effects were common. Liver Transpl 19:690–700, 2013. © 2013 AASLD.
Effects of 1 week of unilateral ankle immobilization on plantar-flexor strength, balance, and walking speed: a pilot study in asymptomatic volunteers.

CONTEXT Ankle immobilization is often used after ankle injury. OBJECTIVE To determine the influence of 1 week's unilateral ankle immobilization on plantar-flexor strength, balance, and walking gait in asymptomatic volunteers. DESIGN Repeated-measures laboratory study. SETTING University laboratory. PARTICIPANTS 6 physically active male participants with no recent history of lower-limb injury. INTERVENTIONS Participants completed a 1-wk period of ankle immobilization achieved through wearing a below-knee ankle cast. Before the cast was applied, as well as immediately, 24 h, and 48 h after cast removal, their plantar-flexor strength was assessed isokinetically, and they completed a single-leg balance task as a measure of proprioceptive function. An analysis of their walking gait was also completed Main Outcome Measures: Peak plantar-flexor torque and balance were used to determine any effect on muscle strength and proprioception after cast removal. Ranges of motion (3D) of the ankle, knee, and hip, as well as walking speed, were used to assess any influence on walking gait. RESULTS After cast removal, plantar-flexor strength was reduced for the majority of participants (P = .063, CI = -33.98 to 1.31) and balance performance was reduced in the immobilized limb (P < .05, CI = 0.84-5.16). Both strength and balance were not significantly different from baseline levels by 48 h. Walking speed was not significantly different immediately after cast removal but increased progressively above baseline walking speed over the following 48 h. Joint ranges of motion were not significantly different at any time point. CONCLUSIONS The reduction in strength and balance after such a short period of immobilization suggested compromised central and peripheral neural mechanisms. This suggestion appeared consistent with the delayed increase in walking speed that could occur as a result of the excitability of the neural pathways increasing toward baseline levels.
Phylogenetic analysis of 83 plastid genes further resolves the early diversification of eudicots

Although Pentapetalae (comprising all core eudicots except Gunnerales) include ≈70% of all angiosperms, the origin of and relationships among the major lineages of this clade have remained largely unresolved. Phylogenetic analyses of 83 protein-coding and rRNA genes from the plastid genome for 86 species of seed plants, including new sequences from 25 eudicots, indicate that soon after its origin, Pentapetalae diverged into three clades: (i) a “superrosid” clade consisting of Rosidae, Vitaceae, and Saxifragales; (ii) a “superasterid” clade consisting of Berberidopsidales, Santalales, Caryophyllales, and Asteridae; and (iii) Dilleniaceae. Maximum-likelihood analyses support the position of Dilleniaceae as sister to superrosids, but topology tests did not reject alternative positions of Dilleniaceae as sister to Asteridae or all remaining Pentapetalae. Molecular dating analyses suggest that the major lineages within both superrosids and superasterids arose in as little as 5 million years. This phylogenetic hypothesis provides a crucial historical framework for future studies aimed at elucidating the underlying causes of the morphological and species diversity in Pentapetalae.
Proteomics in Trypanosoma cruzi – localization of novel proteins to various organelles

The completion of the genome sequence of Trypanosoma cruzi has been followed by several studies of protein expression, with the long‐term aim to obtain a complete picture of the parasite proteome. We report a proteomic analysis of an organellar cell fraction from T. cruzi CL Brener epimastigotes. A total of 396 proteins were identified by LC‐MS/MS. Of these, 138 were annotated as hypothetical in the genome databases and the rest could be assigned to several metabolic and biosynthetic pathways, transport, and structural functions. Comparative analysis with a whole cell proteome study resulted in the validation of the expression of 173 additional proteins. Of these, 38 proteins previously reported in other stages were not found in the only large‐scale study of the total epimastigote stage proteome. A selected set of identified proteins was analyzed further to investigate gene copy number, sequence variation, transmembrane domains, and targeting signals. The genes were cloned and the proteins expressed with a c‐myc epitope tag in T. cruzi epimastigotes. Immunofluorescence microscopy revealed the localization of these proteins in different cellular compartments such as ER, acidocalcisome, mitochondrion, and putative cytoplasmic transport or delivery vesicles. The results demonstrate that the use of enriched subcellular fractions allows the detection of T. cruzi proteins that are undetected by whole cell proteomic methods.
Semi Supervised Logistic Regression

Semi-supervised learning has recently emerged as a new paradigm in the machine learning community. It aims at exploiting simultaneously labeled and unlabeled data for classification. We introduce here a new semi-supervised algorithm. Its originality is that it relies on a discriminative approach to semi-supervised learning rather than a generative approach, as it is usually the case. We present in details this algorithm for a logistic classifier and show that it can be interpreted as an instance of the Classification Expectation Maximization algorithm. We also provide empirical results on two data sets for sentence classification tasks and analyze the behavior of our methods.