Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural correlates of craving and resisting craving for tobacco in nicotine dependent smokers

Craving is a significant factor which can lead to relapse during smoking quit attempts. Attempts to resist urges to smoke during cue‐elicited craving have been shown to activate regions in the brain associated with decision‐making, anxiety regulation and visual processing. In this study, 32 treatment‐seeking, nicotine‐dependent smokers viewed blocks of smoking and neutral cues alternating with rest periods during magnetic resonance imaging scanning in a 3T Siemens scanner (Siemens AG, Erlangen, Bavaria, Germany). While viewing cues or control images, participants were instructed either to ‘allow yourself to crave’ or ‘resist craving. ’ Data were analyzed with FSL 4.1. 5, focused on the smoking cues versus neutral cues contrast, using cluster thresholding (Z > 2.3 and corrected cluster threshold of P = 0.05) at the individual and group levels. During the Crave condition, activation was seen on the left anterior cingulated cortex (LACC), medial prefrontal cortex, left middle cingulate gyrus, bilateral posterior cingulated gyrus and bilateral precuneus, areas associated with attention, decision‐making and episodic memory. The LACC and areas of the prefrontal cortex associated with higher executive functioning were activated during the Resist condition. No clear distinctions between group crave and resist analyses as a whole were seen without taking into account specific strategies used to resist the urge to smoke, supporting the idea that craving is associated with some degree of resisting the urge to smoke, and trying to resist is almost always accompanied by some degree of craving. Different strategies for resisting, such as distraction, activated different regions. Understanding the underlying neurobiology of resisting craving to smoke may identify new foci for treatments.
Analyzing Cost Efficient Production Behavior Under Economies of Scope: A Nonparametric Methodology

In designing a production model for firms that generate multiple outputs, we take as a starting point that such multioutput production refers to economies of scope, which in turn originate from joint input use and input externalities. We provide a nonparametric characterization of cost-efficient behavior under these conditions, and subsequently institute necessary and sufficient conditions for data consistency with such efficient behavior that only include observed firm demand and supply data. We illustrate our methodology by examining the cost efficiency of research programs in economics and business management faculties of Dutch universities. This application shows that the proposed methodology may entail robust conclusions regarding cost-efficiency differences between universities within specific specialization areas, even when using shadow prices to evaluate the different inputs.
Response assessment by combined PET-CT scan versus CT scan alone using RECIST in patients with locally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE RECIST have limitations when applied to potentially curable locally advanced squamous cell carcinoma of the head and neck (SCCHN). [¹⁸F]fluorodeoxyglucose-positron emission tomography (PET) scan may be useful in assessing treatment response and predicting patient outcome. PATIENTS AND METHODS We studied patients with previously untreated stages III-IVb SCCHN treated with primary concurrent chemoradiotherapy on five prospective clinical trials. Response was assessed by clinical exam, computed tomography (CT), and PET portions of combined PET-CT scan ∼8 weeks after completion of chemoradiotherapy. RESULTS Fifty-three patients were analyzed. Complete response (CR) was demonstrated in 42 patients (79%) by clinical exam, 15 (28%) by CT, and 27 (51%) by PET. CR as assessed by PET, but not as assessed by clinical exam or CT using RECIST, correlated significantly with progression-free status (PFS) (P < 0.0001). The 2-year PFS for patients with CR and without CR by PET was 93% and 48%, respectively (P = 0.0002). CONCLUSIONS A negative PET scan on combined PET-CT after chemoradiotherapy is a powerful predictor of outcome in patients receiving curative chemoradiotherapy for SCCHN. PET-CT is indicated for response evaluation in this setting to improve the accuracy of post-treatment assessment by CT.
Hexapeptides That Inhibit Processing of Branched DNA Structures Induce a Dynamic Ensemble of Holliday Junction Conformations*

Background: Anti-microbial hexapeptides trap Holliday junctions and inhibit junction-processing enzymes. Results: Hexapeptides induce multiple conformations and dynamic fluctuations of two Holliday junctions that differ in core sequence. Conclusion: Destabilization of the functional junction conformation likely contributes to inhibition of enzymes that process Holliday junctions. Significance: Ligand-induced conformational dynamics may contribute generally to the action of anti-microbial agents that target specialized DNA structures. Holliday junctions are critical intermediates in DNA recombination, repair, and restart of blocked replication. Hexapeptides have been identified that bind to junctions and inhibit various junction-processing enzymes, and these peptides confer anti-microbial and anti-tumor properties. Earlier studies suggested that inhibition results from stabilization of peptide-bound Holliday junctions in the square planar conformation. Here, we use single molecule fluorescence resonance energy transfer (smFRET) and two model junctions, which are AT- or GC-rich at the branch points, to show that binding of the peptide KWWCRW induces a dynamic ensemble of junction conformations that differs from both the square planar and stacked X conformations. The specific features of the conformational distributions differ for the two peptide-bound junctions, but both junctions display greatly decreased Mg2+ dependence and increased conformational fluctuations. The smFRET results, complemented by gel mobility shift and small angle x-ray scattering analyses, reveal structural effects of peptides and highlight the sensitivity of smFRET for analyzing complex mixtures of DNA structures. The peptide-induced conformational dynamics suggest multiple stacking arrangements of aromatic amino acids with the nucleobases at the junction core. This conformational heterogeneity may inhibit DNA processing by increasing the population of inactive junction conformations, thereby preventing the binding of processing enzymes and/or resulting in their premature dissociation.
Comparison of esmolol to nitroglycerine in controlling hypotension during nasal surgery.

OBJECTIVE The aim of this study was to compare esmolol to nitroglycerine in terms of effectiveness in controlling hypotension during nasal surgery. MATERIALS AND METHODS After approval by our institutional Ethics Committee, 40 patients were recruited and randomized into two drug groups: esmolol (Group E) and nitroglycerine (Group N). In group E, a bolus dose of 500 μg/kg esmolol was administered over 30 sec followed by continuous administration at a dose of 25-300 μg/ kg/min to maintain systolic arterial pressure at 80 mmHg. In group N, nitroglycerine was administered at a dose of 0.5-2 μg/kg/min. RESULTS During the hypotensive period, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, and heart rate were decreased 24%, 33%, 27% and 35%, respectively, in group E (p<0.001, p<0.001, p<0.001, p<0.001) and were decreased 30%, 33%, 34% and 23%, respectively, in group N (p<0.001, p<0.001, p<0.001, p<0.001). The decrease in heart rate was higher in group E during the hypotensive period (p=0.048). During the recovery period, diastolic arterial pressure and heart rate were decreased 9% and 18%, respectively, in group E (p=0.044, p<0.001). Systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure were decreased 7%, 3% and 7%, respectively, in group N (p=0.049, p=0.451, p=0.045). CONCLUSION Esmolol provides hemodynamic stability and good surgical field visibility and should be considered as an alternative to nitroglycerine.
Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI). Methods Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease. Results 39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes. Conclusions Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.
The evolution of clusters in the CLEF cosmological simulation: X‐ray structural and scaling properties

We present results from a study of the X-ray cluster population that forms within the CLEF cosmological hydrodynamics simulation, a large N-body/SPH simulation of the Lambda cold dark matter cosmology with radiative cooling, star formation and feedback. With nearly 100 (kT > 2 keV) clusters at z = 0 and 60 at z = 1, our sample is one of the largest ever drawn from a single simulation and allows us to study variations within the X-ray cluster population both at low and high redshift. The scaled projected temperature and entropy profiles at z = 0 are in good agreement with recent high-quality observations of cool core clusters, suggesting that the simulation grossly follows the processes that structure the intracluster medium (ICM) in these objects. Cool cores are a ubiquitous phenomenon in the simulation at low and high redshift, regardless of a cluster’s dynamical state. This is at odds with the observations and so suggests there is still a heating mechanism missing from the simulation. The fraction of irregular (major merger) systems, based on an observable measure of substructure within X-ray surface brightness maps, increases with redshift, but always constitutes a minority population within the simulation. Using a simple, observable measure of the concentration of the ICM, which correlates with the apparent mass deposition rate in the cluster core, we find a large dispersion within regular clusters at low redshift, but this diminishes at higher redshift, where strong cooling-flow systems are absent in our simulation. Consequently, our results predict that the normalization and scatter of the luminosity‐temperature relation should decrease with redshift; if such behaviour turns out to be a correct representation of X-ray cluster evolution, it will have significant consequences for the number of clusters found at high redshift in X-ray flux-limited surveys.
Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.

BACKGROUND Acetaminophen is a common therapy for fever in patients in the intensive care unit (ICU) who have probable infection, but its effects are unknown. METHODS We randomly assigned 700 ICU patients with fever (body temperature, ≥38°C) and known or suspected infection to receive either 1 g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, cessation of antimicrobial therapy, or death. The primary outcome was ICU-free days (days alive and free from the need for intensive care) from randomization to day 28. RESULTS The number of ICU-free days to day 28 did not differ significantly between the acetaminophen group and the placebo group: 23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen and 22 days (interquartile range, 12 to 25) among patients assigned to placebo (Hodges-Lehmann estimate of absolute difference, 0 days; 96.2% confidence interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%) had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84). CONCLUSIONS Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819.).
Attitudes towards perception and management of pain in rabbits and guinea pigs by a sample of veterinarians in New Zealand

Abstract AIMS: To determine the perceptions of a sample of veterinarians in New Zealand regarding pain and pain management in rabbits and guinea pigs. METHODS: Questionnaires were distributed to all members of the Companion Animal Society, part of the New Zealand Veterinary Association. The questionnaire gathered information on the demographics of respondents, obtained an assessment by veterinarians of the level of pain associated with clinical procedures for rabbits and guinea pigs, established the willingness of respondents to perform these, obtained information on the anaesthetics and analgesics used during these procedures, and the factors associated with selecting different types of drug. The level of knowledge of respondents and interest in continuing education regarding pain recognition and management in these species was also assessed. RESULTS: A total of 155/610 (25.4%) responses were obtained. Rodents and lagomorphs accounted for 0–5% of the total caseload in the practices of most (133/155; 86%) respondents. Anticipated pain scores differed for different procedures (p<0.001) but did not differ between male and female respondents or between species of animal. There were also differences between procedures in the respondents willingness to perform them (p<0.001). Selection of anaesthetics and analgesics was mainly determined by the amount of information available for the species, and ketamine was the drug most commonly used. Many veterinarians felt their level of knowledge regarding the recognition and treatment of pain in rabbits and guinea pigs was inadequate. CONCLUSIONS: Rabbits and guinea pigs represented a small percentage of the caseload of veterinarians in this study. From an animal welfare perspective this may be of concern as, anecdotally, these species are common pets. However, further study regarding the actual number of these animals kept as pets in New Zealand is required for validation. Veterinary perception of anticipated pain, and willingness to perform procedures, varied between procedures, but was not influenced by gender of veterinarian. Many respondents felt their knowledge of issues relating to pain recognition, anaesthesia and analgesia in rabbits and guinea pigs was inadequate. CLINICAL RELEVANCE: Understanding how veterinarians choose to provide analgesia or when they decline to perform surgeries for rabbits and guinea pigs may provide significant information for targeting professional development, and improving animal welfare.
The Deubiquitinase Activity of the Salmonella Pathogenicity Island 2 Effector, SseL, Prevents Accumulation of Cellular Lipid Droplets

ABSTRACT To cause disease, Salmonella enterica serovar Typhimurium requires two type III secretion systems that are encoded by Salmonella pathogenicity islands 1 and 2 (SPI-1 and -2). These secretion systems serve to deliver specialized proteins (effectors) into the host cell cytosol. While the importance of these effectors to promote colonization and replication within the host has been established, the specific roles of individual secreted effectors in the disease process are not well understood. In this study, we used an in vivo gallbladder epithelial cell infection model to study the function of the SPI-2-encoded type III effector, SseL. The deletion of the sseL gene resulted in bacterial filamentation and elongation and the unusual localization of Salmonella within infected epithelial cells. Infection with the ΔsseL strain also caused dramatic changes in host cell lipid metabolism and led to the massive accumulation of lipid droplets in infected cells. This phenotype was directly attributable to the deubiquitinase activity of SseL, as a Salmonella strain carrying a single point mutation in the catalytic cysteine also resulted in extensive lipid droplet accumulation. The excessive buildup of lipids due to the absence of a functional sseL gene also was observed in murine livers during S. Typhimurium infection. These results suggest that SseL alters host lipid metabolism in infected epithelial cells by modifying the ubiquitination patterns of cellular targets.
Acceptability, reliability, and validity of the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39) across languages: a systematic review

Objectives: This systematic review aimed to explore the acceptability, reliability, and validity of the Stroke and Aphasia Quality of Life-39 (SAQOL-39) scale across languages. Data sources: We employed a systematic search of the online databases including MEDLINE (Pubmed), Science direct, Web of science, Psychinfo, Scopus, ProQuest, Google Scholar, and Cochrane library published between 2003 and 2016. Review methods: We used PRISMA guidelines for conducting and reporting this review. Subsequently, screening of the titles and abstracts, extraction of data as well as the appraisal of the quality of relevant studies were carried out. Results: The initial search returned 8185 studies. Subsequent screening and study selection processes narrowed them to 20, needing detailed review. Forward-backward translation scheme was the preferred method for translation of the SAQOL-39 from English to other languages. Mainly, the socio-cultural and linguistic adaptations were performed in the translated versions. Most versions of the SAQOL-39 showed high test-retest reliability and internal consistency. However, several psychometric properties including the validity and responsiveness were seldom reported in these versions. Conclusion: The SAQOL-39 scale showed high acceptability, and reliability across the languages reviewed in this study. Future translations may additionally focus on reporting the validity and responsiveness of the instrument.
Induction of Mammary Gland Development in Estrogen Receptor-α Knockout Mice.

Mammary glands from the estrogen receptor-a knockout (alphaERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted ERalpha signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the alphaERKO mammary phenotype. We report that circulating PRL is reduced in the female alphaERKO mouse. Implantation of an age-matched, heterozygous ERalpha pituitary isograft under the renal capsule of 25-day-old or 12-week-old alphaERKO mice increased circulating PRL and progesterone levels, and induced mammary gland development. Grafted alphaERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL is luteotropic in the alphaERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in alphaERKO mice despite elevated PRL levels. Hormone replacement using pellet implants demonstrated that pharmacological doses of estradiol induced limited mammary ductal elongation, and estradiol in combination with progesterone stimulated lobuloalveolar development. PRL alone or in combination with progesterone or estradiol did not induce alphaERKO mammary growth. Estradiol and progesterone are required for the structural development of the alphaERKO mammary gland, and PRL contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the alphaERKO mammary phenotype appears due to the lack of direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.
Integrated Analysis of Residue Coevolution and Protein Structure in ABC Transporters

Intraprotein side chain contacts can couple the evolutionary process of amino acid substitution at one position to that at another. This coupling, known as residue coevolution, may vary in strength. Conserved contacts thus not only define 3-dimensional protein structure, but also indicate which residue-residue interactions are crucial to a protein’s function. Therefore, prediction of strongly coevolving residue-pairs helps clarify molecular mechanisms underlying function. Previously, various coevolution detectors have been employed separately to predict these pairs purely from multiple sequence alignments, while disregarding available structural information. This study introduces an integrative framework that improves the accuracy of such predictions, relative to previous approaches, by combining multiple coevolution detectors and incorporating structural contact information. This framework is applied to the ABC-B and ABC-C transporter families, which include the drug exporter P-glycoprotein involved in multidrug resistance of cancer cells, as well as the CFTR chloride channel linked to cystic fibrosis disease. The predicted coevolving pairs are further analyzed based on conformational changes inferred from outward- and inward-facing transporter structures. The analysis suggests that some pairs coevolved to directly regulate conformational changes of the alternating-access transport mechanism, while others to stabilize rigid-body-like components of the protein structure. Moreover, some identified pairs correspond to residues previously implicated in cystic fibrosis.
Perspectives on promoting breastmilk feedings for premature infants during a quality improvement project.

OBJECTIVE This study investigated clinicians' perspectives during a quality improvement project to promote breastmilk feedings in premature infants. STUDY DESIGN From 2009 to 2010, 11 hospitals in the California Perinatal Quality Care Collaborative participated in a project to promote breastmilk feedings in premature infants. Audio recordings of monthly meetings held to encourage sharing of ideas were analyzed using qualitative methods to identify common themes related to barriers and solutions to breastmilk feeding promotion. RESULTS Two broad categories were noted: communication and team composition. Communication subthemes included (1) communication among hospital staff, including consistent documentation, (2) communication with family, and (3) communication between transfer hospitals. Team composition subthemes included (4) importance of physician buy-in and (5) integrated teams designed to empower leaders. CONCLUSIONS Optimizing communication among health professionals and parents and improving team composition may be key components of facilitating breastmilk feeding promotion in premature infants.