Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Interpersonal Psychotherapy and other Psychodynamic Therapies versus ‘Treatment as Usual’ in Patients with Major Depressive Disorder

Background Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Methods/Principal Findings Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed ‘interpersonal psychotherapy’ and only one trial assessed ‘psychodynamic psychotherapy’. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference −3.12 (95% confidence interval −4.39 to −1.86;P<0.00001), no heterogeneity) compared with ‘treatment as usual’. Trial sequential analysis confirmed this result. Discussion We did not find convincing evidence supporting or refuting the effect of interpersonal psychotherapy or psychodynamic therapy compared with ‘treatment as usual’ for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed.
Macrophage HIF-2α Ameliorates Adipose Tissue Inflammation and Insulin Resistance in Obesity

In obesity, adipose tissue macrophages (ATMs) play a key role in mediating proinflammatory responses in the adipose tissue, which are associated with obesity-related metabolic complications. Recently, adipose tissue hypoxia has been implicated in the regulation of ATMs in obesity. However, the role of hypoxia-inducible factor (HIF)-2α, one of the major transcription factors induced by hypoxia, has not been fully elucidated in ATMs. In this study, we demonstrate that elevation of macrophage HIF-2α would attenuate adipose tissue inflammation and improve insulin resistance in obesity. In macrophages, overexpression of HIF-2α decreased nitric oxide production and suppressed expression of proinflammatory cytokines through induction of arginase 1. HIF-2α–overexpressing macrophages alleviated proinflammatory responses and improved insulin resistance in adipocytes. In contrast, knockdown of macrophage HIF-2α augmented palmitate-induced proinflammatory gene expression in adipocytes. Furthermore, compared with wild-type mice, Hif-2α heterozygous-null mice aggravated insulin resistance and adipose tissue inflammation with more M1-like ATMs upon high-fat diet (HFD). Moreover, glucose intolerance in HFD-fed Hif-2α heterozygous-null mice was relieved by macrophage depletion with clodronate treatment, implying that increase of proinflammatory ATMs is responsible for insulin resistance by haplodeficiency of Hif-2α upon HFD. Taken together, these data suggest that macrophage HIF-2α would counteract the proinflammatory responses to relieve obesity-induced insulin resistance in adipose tissue.
Can We Use Human Judgments to Determine the Discount Rate?

It has been suggested that the long‐term discount rate for environmental goods should decrease at longer delays. One justification for this suggestion is that human judgments support it. This article presents an experiment showing that judgments concerning discount rates are internally inconsistent. These results point to potential problems with the use of judgments referenda for determining discount rates in cost‐benefit analyses.
Behavior of Left Ventricular Mechanoreceptors with Myelinated and Nonmyelinated Afferent Vagal Fibers in Cats

The purpose of this study was to determine the behavior of left ventricular mechano-receptors with myelinated vagal afferents and to compare them with endings with nonmyelinated vagal afferents. Single unit activity was recorded from 13 endings with nonmyelinated vagal afferents (conduction velocity 2.1 ± 0.3 m/sec) and from 16 endings with myelinated vagal afferents (conduction velocity 7.3 ± 1.3 m/sec). Resting discharge frequencies of nonmyelinated afferents and of myelinated vagal afferents were 1.7 ± 0.3 and 2.7 ± 0.5 imp/sec (P < 0.1), respectively (at left ventricular end diastolic pressure of 6 mm Hg for both groups). Ten of 16 myelinated vagal afferents had pulse synchronous discharge under basal condition, whereas only 3 of 13 nonmyelinated vagal afferents had such activity. During aortic occlusion, the discharge of myelinated vagal afferents increased 1.7 ± 0.3 imp/sec per mm Hg, whereas nonmyelinated vagal afferents increased signifi-cantly (P < 0.05) less (0.5 ± 0.1 imp/sec per mm Hg). Discharge for both groups was linearly related to left ventricular end-diastolic pressure but not to left ventricular systolic pressure. Increases in left ventricular systolic pressure alone did not increase firing for either group. During aortic occlusion, the maximum discharge rates of myelinated vagal afferents (43 ± 7 imp/sec) were significantly higher than those of nonmyelinated vagal afferents (14 ± 3 imp/sec) at left ventricular end-diastolic pressure of 30 ± 2 and 24 ± 2 mm Hg, respectively. Both groups increased their discharge during volume expansion with myelinated vagal afferents showing greater sensitivity than nonmyelinated vagal afferents. All endings studied were in the inferoposterior wall of the left ventricle. All nonmyelinated vagal afferents were in or near the epicardium. In contrast, myelinated vagal afferents were equally distributed between the endocardium and the epicardium. Myelinated vagal afferents had discrete receptive fields (1–2 mm2) whereas those of nonmyelinated vagal afferents were much larger (1 cm2). In conclusion, the discharge of left ventricular endings with nonmyelinated vagal afferents and myelinated vagal afferents both appear to be determined mainly by changes in left ventricular end-diastolic pressure. They may be located at different depths in the left ventricular wall. Myelinated vagal afferents have greater sensitivity and maximum firing frequencies than nonmyelinated vagal afferents.
Structure–function analysis of the GmRIC1 signal peptide and CLE domain required for nodulation control in soybean

Legumes control the nitrogen-fixing root nodule symbiosis in response to external and internal stimuli, such as nitrate, and via systemic autoregulation of nodulation (AON). Overexpression of the CLV3/ESR-related (CLE) pre-propeptide-encoding genes GmNIC1 (nitrate-induced and acting locally) and GmRIC1 (Bradyrhizobium-induced and acting systemically) suppresses soybean nodulation dependent on the activity of the nodulation autoregulation receptor kinase (GmNARK). This nodule inhibition response was used to assess the relative importance of key structural components within and around the CLE domain sequences of these genes. Using a site-directed mutagenesis approach, mutants were produced at each amino acid within the CLE domain (RLAPEGPDPHHN) of GmRIC1. This approach identified the Arg1, Ala3, Pro4, Gly6, Pro7, Asp8, His11, and Asn12 residues as critical to GmRIC1 nodulation suppression activity (NSA). In contrast, none of the mutations in conserved residues outside of the CLE domain showed compromised NSA. Chimeric genes derived from combinations of GmRIC1 and GmNIC1 domains were used to determine the role of each pre-propeptide domain in NSA differences that exist between the two peptides. It was found that the transit peptide and CLE peptide regions of GmRIC1 significantly enhanced activity of GmNIC1. In contrast, the comparable GmNIC1 domains reduced the NSA of GmRIC1. Identification of these critical residues and domains provides a better understanding of how these hormone-like peptides function in plant development and regulation.
Assessment of ground-based atmospheric observations for verification of greenhouse gas emissions from an urban region

International agreements to limit greenhouse gas emissions require verification to ensure that they are effective and fair. Verification based on direct observation of atmospheric greenhouse gas concentrations will be necessary to demonstrate that estimated emission reductions have been actualized in the atmosphere. Here we assess the capability of ground-based observations and a high-resolution (1.3 km) mesoscale atmospheric transport model to determine a change in greenhouse gas emissions over time from a metropolitan region. We test the method with observations from a network of CO2 surface monitors in Salt Lake City. Many features of the CO2 data were simulated with excellent fidelity, although data-model mismatches occurred on hourly timescales due to inadequate simulation of shallow circulations and the precise timing of boundary-layer stratification and destratification. Using two optimization procedures, monthly regional fluxes were constrained to sufficient precision to detect an increase or decrease in emissions of approximately 15% at the 95% confidence level. We argue that integrated column measurements of the urban dome of CO2 from the ground and/or space are less sensitive than surface point measurements to the redistribution of emitted CO2 by small-scale processes and thus may allow for more precise trend detection of emissions from urban regions.
Clinical characteristics of essential tremor in Taiwan: an exploratory‐comparative study

Background: There are few large‐scale clinical analyses of essential tremor (ET) in Asia. We studied the detailed clinical profile with emphasizing the age of onset, tremor location, specific tremor patterns, and rate of progression (ROP) to delineate the characteristics of Taiwanese ET patients and found the difference between the Taiwanese and the Caucasians ET patients.
Importance of neural fibroblasts in the regeneration of nerve.

It IS generally agreed that the regeneration of peripheral nerve is accomplished by the regrowth of axis-cylinders in close relation to the remnants of the Schwann cells of the degenerated nerve. Whether the Schwann bands form a medium favoring active growth or provide simply a passive linear path without obstruction is still debated. 1 Few 2 deny the Schwann cell any part in the process of conduction of the regenerating fiber. There is no doubt, however, that the Schwann nucleus determines the maturation of the myelin sheath at a later stage of restoration. When there has been a breach in continuity in the nerve, the outgrowing axis-cylinder bridges the gap, but the factors which aid or hinder this process are imperfectly understood. These problems have been reviewed at length by Ramon y Cajal 3 and, more recently, by Young 1 and by Weiss. 4 They are of primary importance in
Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery

The CRISPR/Cas9 system is a robust genome editing technology that works in human cells, animals and plants based on the RNA-programmed DNA cleaving activity of the Cas9 enzyme. Building on previous work (Jinek et al., 2013), we show here that new genetic information can be introduced site-specifically and with high efficiency by homology-directed repair (HDR) of Cas9-induced site-specific double-strand DNA breaks using timed delivery of Cas9-guide RNA ribonucleoprotein (RNP) complexes. Cas9 RNP-mediated HDR in HEK293T, human primary neonatal fibroblast and human embryonic stem cells was increased dramatically relative to experiments in unsynchronized cells, with rates of HDR up to 38% observed in HEK293T cells. Sequencing of on- and potential off-target sites showed that editing occurred with high fidelity, while cell mortality was minimized. This approach provides a simple and highly effective strategy for enhancing site-specific genome engineering in both transformed and primary human cells. DOI: http://dx.doi. org/10.7554/eLife.04766. 001
Targeting B-cell receptor signaling kinases in chronic lymphocytic leukemia: the promise of entospletinib

The B-cell receptor signaling pathway has emerged as an important therapeutic target in chronic lymphocytic leukemia and other B-cell malignancies. Novel agents have been developed targeting the signaling enzymes spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase, and phosphoinositide 3-kinase delta. This review discusses the rationale for targeting these enzymes, as well as the preclinical and clinical evidence supporting their role as therapeutic targets, with a particular focus on SYK inhibition with entospletinib.
Human-Related Factors Regulate the Spatial Ecology of Domestic Cats in Sensitive Areas for Conservation

Background Domestic cats ranging freely in natural areas are a conservation concern due to competition, predation, disease transmission or hybridization with wildcats. In order to improve our ability to design effective control policies, we investigate the factors affecting their numbers and space use in natural areas of continental Europe. Methodology/Principal Findings We describe the patterns of cat presence, abundance and space use and analyse the associated environmental and human constraints in a well-preserved Mediterranean natural area with small scattered local farms. We failed in detecting cats in areas away from human settlements (trapping effort above 4000 trap-nights), while we captured 30 individuals near inhabited farms. We identified 130 cats, all of them in farms still in use by people (30% of 128 farms). All cats were free-ranging and very wary of people. The main factor explaining the presence of cats was the presence of people, while the number of cats per farm was mostly affected by the occasional food provisioning with human refuse and the presence of people. The home ranges of eight radio tagged cats were centred at inhabited farms. Males went furthest away from the farms during the mating season (3.8 km on average, maximum 6.3 km), using inhabited farms as stepping-stones in their mating displacements (2.2 km of maximum inter-farm distance moved). In their daily movements, cats notably avoided entering in areas with high fox density. Conclusions The presence, abundance and space use of cats were heavily dependent on human settlements. Any strategy aiming at reducing their impact in areas of conservation concern should aim at the presence of settlements and their spatial spread and avoid any access to human refuse. The movements of domestic cats would be limited in areas with large patches of natural vegetation providing good conditions for other carnivore mammals such as red foxes.
Geosocial Recommender Systems

Daily life is full of location-related decisions: where to go on vacation, which house to buy, which job to apply for, etc. These decisions are not only influenced by the characteristics of this holiday home, house, or company, but also by the region it is located in. What is the distance to the beach, the nearest train station, or the schools and kindergartens? In this thesis, that is inspired by the case of an online holiday home broker, we introduce the geosocial recommender system GeoSoRS: a system that supports people in their decision-making process for location-bound objects, such as holiday homes or real estate, using public data only, to keep the threshold for using GeoSoRS to a minimum. Current location-based recommender systems are focused on the recommendation of a single point-of-interest (POI), based on the characteristics of that POI only. In this thesis, we combine this information about a region in its geoprofile: a description of those characteristics of a region that are relevant to the decision to be made. We try to find the match between users and location-bound objects through a user profile and a geoprofile respectively, and look at the shared interests that users have and regions can satisfy. We find this match by answering four main research questions. First of all, we present a software architecture suitable for the combination of web content, social media data, user-generated content (UGC) and several other sources that provide useful information for recommendation selection. In the second, and largest, part of the thesis, we detect which places are visited by which people through a three-step process: (1) POI collection from the web, (2) estimation of their shape and size, called their polygon-of-interest, using public data only, and (3) matching such two-dimensional polygons-of-interest with user trajectories to detect true visits. Thirdly, we find a way to assess the quality of UGC, based on trajectory characteristics of their creators. We introduce a method for human pattern recognition in trajectory data, and show how the outcome of this pattern detection can be used for the creation of UGC quality prediction models. With the fourth and final research question, we focus on knowledge-based recommendations, combining user interests with the interests that can be satisfied at certain locations. We combine social media data, public generic knowledge-bases and tagged item sets to recommend items from multiple domains, among which holiday homes.
Differences in the Electrophysiological Response of Canine Ventricular Epicardium and Endocardium to Ischemia Role of the Transient Outward Current

BackgroundAcute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (It.) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent I,. in epicardium than in endocardium. Methods and ResultsIsolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20%o shortening in endocardium. 4-Aminopyridine, an I,0 inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of I, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after premature beats. Similar results were obtained in tissues and myocytes obtained from the same myocardial layers, suggesting that the differential sensitivities of epicardium and endocardium to ischemia are largely a result of inherent differences in cellular properties. ConclusionOur data suggest that the presence of a prominent It. in epicardium but not endocardium contributes importantly to the selective electrical depression of epicardium by simulated ischemia. The repolarizing influence of It. serves to amplify the ischemia-induced changes in inward (Ica and INa) and outward (calcium-activated) currents. By facilitating loss of the dome in epicardium, I,. contributes to the development of a marked dispersion of repolarization between normal and ischemic epicardium and between epicardium and endocardium, thereby providing the electrophysiological substrate for the genesis of reentrant arrhythmias.
Release mechanism and parameter estimation in drug-eluting stent systems: analytical solutions of drug release and tissue transport

Drug-eluting stents have significantly improved the treatment of coronary artery disease. They offer reduced rates of restenosis compared with their bare-metal predecessors and are the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been approved for use in humans since 2002 and yet, despite the intensive research activity over the past decade, the drug release mechanism(s) and the uptake into the arterial wall are still poorly understood. While stent manufacturers have focussed primarily on empirical methods, several mathematical models have appeared in the literature considering the release problem, the uptake problem and also the coupled problem. However, two significant challenges that remain are in understanding the drug release mechanism(s) and also the determination of the various parameters characterizing the system. These include drug diffusion coefficients and dissolution constants in the stent polymer coating as well as drug diffusion coefficients, binding/uptake rates and the magnitude of the transmural convection in the arterial wall. In this paper we attempt to address these problems. We provide analytical solutions which, when compared with appropriate experiments, may allow the various parameters of the system to be estimated via the inverse problem. The analytical solutions which we provide here for drug release in vitro may thus be used as a tool for providing insights into the mechanism(s) of release.
Brief Rewarming Blunts Hypothermia-Induced Alterations in Sensation, Motor Drive and Cognition

Background: It is well known that cold exposure experienced during occupational or recreational activities may adversely affect motor, cognitive performance, and health. Most research has used prolonged passive external rewarming modalities and focused on the direct effects on the kinetics of physiological and psychological responses in hypothermic subjects. However, the brief whole body rewarming effects on physiological and psychological responses in parallel with functional consequences on cognitive and neurophysiological functions have not been investigated. This study explores these effects in 12 healthy young men. Methods: Subjects (20 ± 1 years) participated in 4 randomized trials, which were designed to compare the effects of whole-body brief (5-min) rewarming in 37°C water with rewarming for the same duration in 24°C (air) thermoneutral environment in mildly hypothermic subjects. After each rewarming, indicators of neuromuscular function (reflexes, central activation ratio, electromyography of exercising muscle, and contractile properties of calf muscles) and cognitive function (attention, simple motor speed, and information processing speed) were assessed. Results: Compared to rewarming in thermoneutral environment, after brief rewarming in 37°C water, significantly lower metabolic heat production (MHP) (206 ± 33.4 vs. 121.9 ± 24.3 W·m2, P < 0.01), heart rate (76 ± 16 vs. 60 ± 12 b·min−1, P < 0.01), cold strain (6.4 ± 3.1 vs. 5.3 ± 2.7, P < 0.01), improved thermal comfort and induced cessation of shivering were found. Electrically induced maximum torque amplitudes increased (P100, 102.8 ± 21.3 vs. 109.2 ± 17.5 Nm and PTT100, 83.1 ± 17.1 vs. 92.7 ± 16.0 Nm, P < 0.05), contraction half-relaxation time decreased (599.0 ± 53.8 vs. 589.0 ± 56.3 ms, P < 0.05), and Mmax-wave latency shortened (17.5 ± 2.2 vs. 15.6 ± 2.0 ms, P < 0.05) after 37°C water rewarming. Unlike rewarming in thermoneutral environment, 37°C water rewarming blunted the hypothermia-induced alterations in neural drive transmission (4.3 ± 0.5 vs. 3.4 ± 0.8 mV H-reflex and 4.9 ± 0.2 vs. 4.4 ± 0.4 mV V-wave, P < 0.05), which increased central fatigue during a 2-min maximum load (P < 0.05). Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P < 0.05). Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for sensation, motor drive, and cognition, despite the fact that rectal and deep muscle temperature remained lowered.