Miracle-dz/UniFAR-FTUs huggingface dataset:
A Multisite, Randomized Clinical Trial of Virtual Reality and Prolonged Exposure Therapy for Active Duty Soldiers with PTSD

Abstract : This randomized, clinical trial was designed to extend recruitment to an additional active duty site (Womack Army Medical Center at Ft Bragg) in support of a previously funded clinical trial to evaluate the efficacy of virtual reality exposure therapy (VRET) and prolonged exposure therapy (PE) with a waitlist (WL) group in the treatment of posttraumatic stress disorder (PTSD) in active duty (AD) Soldiers with combat-related trauma. Soldiers with PTSD from deployments to Iraq or Afghanistan were randomized to 10 sessions of either PE or VRE or were assigned to a minimal attention wait list. All assessments were conducted by a psychologist blind to treatment group. External, independent treatment fidelity reviews were conducted for both treatments. Service members were assessed before randomization, after 5 sessions, at posttreatment, and 3- and 6-months posttreatment. PTSD was assessed with the Clinician Administered PTSD Scale (CAPS). Difficulties with personnel, a slow pace of recruitment, and ultimately the analysis of the data from the original study site called into question the value of continuing this effort, which resulted in the study ending with 23 subjects randomized.
Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli

The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.
Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B‐exposed keratinocytes as a mechanism of autoantigen processing

Background The skin has long been recognized as a prominent target tissue in systemic lupus erythematosus (SLE) which plays a crucial role in the initiation and perpetuation of the autoimmune reaction cascade as a consequence of ultraviolet (UV)‐induced keratinocyte apoptosis. Antibodies against IFI16 (interferon‐inducible protein 16) have been detected in the sera of patients with SLE.
eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition

Recognition of the methyl-7-guanosine (m7G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E–cap recognition is mediated via complementary charge interactions of the positively charged m7G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m7G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3–cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.
Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain

Insufficient sleep is associated with obesity, yet little is known about how repeated nights of insufficient sleep influence energy expenditure and balance. We studied 16 adults in a 14- to 15-d-long inpatient study and quantified effects of 5 d of insufficient sleep, equivalent to a work week, on energy expenditure and energy intake compared with adequate sleep. We found that insufficient sleep increased total daily energy expenditure by ∼5%; however, energy intake—especially at night after dinner—was in excess of energy needed to maintain energy balance. Insufficient sleep led to 0.82 ± 0.47 kg (±SD) weight gain despite changes in hunger and satiety hormones ghrelin and leptin, and peptide YY, which signaled excess energy stores. Insufficient sleep delayed circadian melatonin phase and also led to an earlier circadian phase of wake time. Sex differences showed women, not men, maintained weight during adequate sleep, whereas insufficient sleep reduced dietary restraint and led to weight gain in women. Our findings suggest that increased food intake during insufficient sleep is a physiological adaptation to provide energy needed to sustain additional wakefulness; yet when food is easily accessible, intake surpasses that needed. We also found that transitioning from an insufficient to adequate/recovery sleep schedule decreased energy intake, especially of fats and carbohydrates, and led to −0.03 ± 0.50 kg weight loss. These findings provide evidence that sleep plays a key role in energy metabolism. Importantly, they demonstrate physiological and behavioral mechanisms by which insufficient sleep may contribute to overweight and obesity.
Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study.

BACKGROUND Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes of death and survival rates of RRT for ESRD due to MM or LCDD in the ERA-EDTA Registry. METHODS Thirteen national registries providing data on patients who started RRT from 1986-2005 to the ERA-EDTA Registry participated. Incidence per million population (pmp) of RRT for ESRD due to MM or LCDD and other causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. RESULTS Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986-1990 to 2.52 pmp in 2001-2005. MM and LCDD patients compared to non-MM patients were older and a higher percentage was on haemodialysis at day 91 after the start of RRT. The most common causes of death in MM and LCDD patients were malignancy (36.1%), cardiovascular causes (17.2%) and infection (14.7%). MM and LCDD patients had a 2.77 (95% CI, 2.65-2.90) higher risk of death compared to non-MM patients. The unadjusted median survival on RRT was 0.91 years in MM and LCDD patients and 4.46 years in non-MM patients. During follow-up, 35 patients were transplanted and their mean survival was 9.6 years. CONCLUSION The incidence of RRT for ESRD due to MM or LCDD has increased over the past 20 years in Europe. The median patient survival on RRT for MM and LCDD patients was 0.91 years, compared to 4.46 years for non-MM patients. These results suggest that dialysis, and in selected cases even transplantation, should be offered to MM and LCDD patients.
Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder

Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genome-wide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), gene-expression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment. These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.
Low‐Temperature Synthesis of Large‐Scale Molybdenum Disulfide Thin Films Directly on a Plastic Substrate Using Plasma‐Enhanced Chemical Vapor Deposition

By plasma-enhanced chemical vapor deposition, a molybdenum disulfide (MoS2 ) thin film is synthesized directly on a wafer-scale plastic substrate at below 300 °C. The carrier mobility of the films is 3.74 cm(2) V(-1) s(-1) . Also, humidity is successfully detected with MoS2 -based sensors fabricated on the flexible substrate, which reveals its potential for flexible sensing devices.
Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells

Significance Many viruses encode proteases that cleave both viral and host substrates. Arteriviruses encode such a dual-specificity protease (PLP2) that removes ubiquitin from cellular proteins involved in host immunity. Based on a 3D structure of PLP2, we engineered the protease to have diminished deubiquitinating activity without affecting its activity toward its viral substrate. Viruses expressing such engineered proteases displayed a significantly weakened ability to evade host immune responses. This result demonstrates a crucial role for PLP2 in arterivirus immune evasion and opens new possibilities for developing improved attenuated virus vaccines against economically important arteriviruses and other viruses encoding similar dual-specificity proteases. Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. To dissect this dual specificity, which relies on a single catalytic site, we determined the crystal structure of equine arteritis virus PLP2 in complex with ubiquitin (1.45 Å). PLP2 binds ubiquitin using a zinc finger that is uniquely integrated into an exceptionally compact OTU-domain fold that represents a new subclass of zinc-dependent OTU DUBs. Notably, the ubiquitin-binding surface is distant from the catalytic site, which allowed us to mutate this surface to significantly reduce DUB activity without affecting polyprotein cleavage. Viruses harboring such mutations exhibited WT replication kinetics, confirming that PLP2-mediated polyprotein cleavage was intact, but the loss of DUB activity strikingly enhanced innate immune signaling. Compared with WT virus infection, IFN-β mRNA levels in equine cells infected with PLP2 mutants were increased by nearly an order of magnitude. Our findings not only establish PLP2 DUB activity as a critical factor in arteriviral innate immune evasion, but the selective inactivation of DUB activity also opens unique possibilities for developing improved live attenuated vaccines against arteriviruses and other viruses encoding similar dual-specificity proteases.
ELUDING THE PRINCIPLES OF MEDICAL ETHICS – HISTORICAL ASPECTS OF CARBON MONOXIDE USE

Carbon monoxide has been used as a method of suicide and execution ever since ancient times. Nowadays most deaths due to carbon monoxide poisoning are accidental. Still, even in the last decades, this colourless and odourless gas has been used as a method of euthanasia and medically assisted suicide. Dr. Jack Kevorkian, pathologist, stated that he had helped more than 130 people in committing suicide, using in the vast majority of cases a cylinder with carbon monoxide attached through a hose to a facial mask (Mercitron). During World War II, carbon monoxide has been used as means of euthanasia, both in the Action T4 program (euthanasia program for the terminally ill and for persons with physical and mental disabilities) and in the Nazi extermination camps. In both cases, the extreme violation of the principles of medical ethics (disregard for the principles of personal autonomy, beneficence and non-maleficence) and the failure to comply with the precepts of the Hippocratic Oath (”.measures for the benefit of the sick according to my ability and judgment; I will keep them from harm and injustice. I will give no deadly medicine to any one if asked, nor suggest any such counsel. ”) are noticed.
Atomic structure and hierarchical assembly of a cross-β amyloid fibril

The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale—including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy—we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.
Rotavirus mRNAS are released by transcript-specific channels in the double-layered viral capsid

Rotaviruses are the single most common cause of fatal and severe childhood diarrheal illness worldwide (>125 million cases annually). Rotavirus shares structural and functional features with many viruses, such as the presence of segmented double-stranded RNA genomes selectively and tightly packed with a conserved number of transcription complexes in icosahedral capsids. Nascent transcripts exit the capsid through 12 channels, but it is unknown whether these channels specialize in specific transcripts or simply act as general exit conduits; a detailed description of this process is needed for understanding viral replication and genomic organization. To this end, we developed a single molecule assay for capturing and identifying transcripts extruded from transcriptionally active viral particles. Our findings support a model in which each channel specializes in extruding transcripts of a specific segment that in turn is linked to a single transcription complex. Our approach can be extended to study other viruses and transcription systems.
Le cancer du poumon non à petites cellules : d’hier à aujourd’hui

Resume Le cancer du poumon est une maladie qui frappe annuellement plus de 20 000 Canadiens. Il demeure la principale cause de deces par cancer au Canada. Le cancer du poumon non a petites cellules (CPNAPC), pour sa part, represente plus de 80 % des nouveaux cas de cancer du poumon nouvellement diagnostiques. Il s’agit d’une maladie au pronostic sombre puisque plus de 50 % des patients sont diagnostiques a un stade avance de la maladie (stade IIIb ou IV). En stade precoce (stade I ou II), la resection chirurgicale de la tumeur offre la meilleure chance de guerison complete de la maladie. D’un autre cote, la chimiotherapie a base d’un derive des platines s’avere un outil therapeutique important pour les patients presentant un CPNAPC en stade plus avance (stade III ou IV). Abstract Lung cancer is a disease that affects more than 20,000 Canadians each year. It is still the primary cause of death by cancer in Canada. First off, non small-cell lung cancer (NSCLC) is accountable for more than 80% of the newly-diagnosed cases. It is a disease with a very dark prognosis because more than 50% of patients are being diagnosed at a later stage (Stage IIIb or IV). In earlier stages (I or II), the surgical resection of the tumour offers the best chance of total recovery. From another perspective, chemotherapy based on a movement of plates proves to be a very important therapeutic tool for patients stricken by an advancedstage of NSCLC (Stage IIIb or IV). In the course of this article, we will bring you up to date as to what we know about non small-cell lung cancer. First, once again, we will take a good look at the histological classification of this type of cancer, the related-clinical symptoms, the etiology and the risk factors, the diagnosis, the stage determination of the disease and the prognosis. Then, we will elaborate on the various treatment methods currently used throughout the different stages of the disease.
Dosimetry and Optimisation in High Dose Fluoroscopic and Fluorographic Procedures

This thesis describes the search for a practical skin dosimetry method for cardiac catheterization procedures, and the application of an optimisation strategy in barium enema imaging. Kodak EDR2 film was characterised across the range of exposure conditions used in the cardiac catheterization laboratory. Its dose-response curve was modelled using a novel equation, and overall uncertainty in film response was estimated. The film saturated at 1 Gy, limiting its usefulness for skin dosimetry. Its performance was found to be strongly dependent on beam filtration, an aspect that had not previously been studied. The film was then used to measure skin doses to patients undergoing coronary angiograms and angioplasties. For angiograms, all skin doses were well below 1 Gy. For angioplasties, 23% of films showed localised saturation, indicating peak skin doses of at least 1 Gy. Dose-area-product was shown to be a poor predictor of high peak skin dose. A mathematical model was developed and software written, to calculate patient skin dose maps from exposure and projection data stored in the image files. This offered a practical method for assessing the magnitude and approximate location of the peak skin dose. Accuracy was limited by a lack of information regarding fluoroscopic exposures, couch position and beam limitation. After including an estimated contribution from fluoroscopy, the model successfully identified those patients whose skin doses exceeded 1 Gy. Following a baseline survey of local barium enema practice, several dose reduction methods were considered. It was decided to introduce copper filtration. 0.1 mm copper reduced mean patient DAP by 37%, without any measurable difference in contrast detail detectability. A detailed phantom study determined the optimal copper thickness as 0.3 mm. This reduced mean patient DAP by 55%, relative to the baseline survey. A visual grading analysis study showed no significant difference in clinical image quality.
Coupling social attention to the self forms a network for personal significance

Prior social psychological studies show that newly assigned personal significance can modulate high-level cognitive processes, e.g., memory and social evaluation, with self- and other-related information processed in dissociated prefrontal structure: ventral vs. dorsal, respectively. Here, we demonstrate the impact of personal significance on perception and show the neural network that supports this effect. We used an associative learning procedure in which we “tag” a neutral shape with a self-relevant label. Participants were instructed to associate three neutral shapes with labels for themselves, their best friend, or an unfamiliar other. Functional magnetic resonance imaging data were acquired while participants judged whether the shape-label pairs were maintained or swapped. Behaviorally, participants rapidly tagged a neutral stimulus with self-relevance, showing a robust advantage for self-tagged stimuli. Self-tagging responses were associated with enhanced activity in brain regions linked to self-representation [the ventral medial prefrontal cortex (vmPFC)] and to sensory-driven regions associated with social attention [the left posterior superior temporal sulcus (LpSTS)]. In contrast, associations formed with other people recruited a dorsal frontoparietal control network, with the two networks being inversely correlated. Responses in the vmPFC and LpSTS predicted behavioral self-bias effects. Effective connectivity analyses showed that the vmPFC and the LpSTS were functionally coupled, with the strength of coupling associated with behavioral self-biases. The data show that assignment of personal social significance affects perceptual matching by coupling internal self-representations to brain regions modulating attentional responses to external stimuli.
As Proud As We Are: A Journey of Educational Achievement and Learning for Mature Maori Computing Students

In recent years New Zealand has seen an upsurge of mature adult Maori students who have returned to full time studies either at a University, Waanga or Polytechnic tertiary institutions. The Waikato Institute of Technology is one such institution that has seen a phenomenal growth of mature Maori students returning to study. This tertiary institution provides a wide range of qualifications across the disciplines of business, industry, commerce, technology and the arts. Much has been written in recent years of Maori who have returned to full time study. However, the literature is very sparse on indigenous students who have successfully completed a computer degree. This study explores the experiences of some of these adult students who have graduated with a Bachelor of Information Technology Degree (BIT) with an insight to understanding how they have all become academically successful in a discipline which is predominantly seen as non-Maori orientated.