Miracle-dz/UniFAR-FTUs huggingface dataset:
Working memory training and high magnitude incentives for youth cannabis use: A SMART pilot trial.

The purpose of this sequential multiple-assignment randomization treatment pilot study was to examine if (a) adding working memory training to contingency management (CM) for youth with cannabis use disorder (CUD) and (b) switching nonresponding youth to higher magnitude CM incentives boosts outcomes. In Phase 1, youth with CUD (n = 59, M age = 16, male = 71%) attending an intensive outpatient program were randomly assigned to 14 weeks of CM only or CM plus working memory training (WMT). In Week 4, a Phase 2 treatment was assigned. Those with negative urine drug tests (responders) continued in their Phase 1 treatment. Those who were drug positive (nonresponders) were randomly assigned to remain in their Phase 1 treatment or to higher magnitude CM. Zero-inflated negative binomial models comparing those assigned to CM versus CM + WMT indicated no differences in the likelihood of having ≥ 1 week of continuous abstinence or longer abstinence duration. Those assigned to WMT showed greater but nonsignificant improvements in working memory (n = 35; β = .69, p = .06). Working memory improvements were associated with achieving any abstinence (odds ratio = 3.50, 95% CI [1.01, 12.10], p = .05). Phase 2 randomization to higher magnitude CM did not boost outcomes. Overall results suggest that WMT appears promising, but the sample size was small, attrition was high, and replication is important. Alternative strategies should continue to be explored to improve outcomes for adolescent substance use disorders, such as different approaches for nonresponders, tailoring to other baseline or response characteristics, or more robust first-line interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Complete Genomes of Symbiotic Cyanobacteria Clarify the Evolution of Vanadium-Nitrogenase

Abstract Plant endosymbiosis with nitrogen-fixing cyanobacteria has independently evolved in diverse plant lineages, offering a unique window to study the evolution and genetics of plant–microbe interaction. However, very few complete genomes exist for plant cyanobionts, and therefore little is known about their genomic and functional diversity. Here, we present four complete genomes of cyanobacteria isolated from bryophytes. Nanopore long-read sequencing allowed us to obtain circular contigs for all the main chromosomes and most of the plasmids. We found that despite having a low 16S rRNA sequence divergence, the four isolates exhibit considerable genome reorganizations and variation in gene content. Furthermore, three of the four isolates possess genes encoding vanadium (V)-nitrogenase (vnf), which is uncommon among diazotrophs and has not been previously reported in plant cyanobionts. In two cases, the vnf genes were found on plasmids, implying possible plasmid-mediated horizontal gene transfers. Comparative genomic analysis of vnf-containing cyanobacteria further identified a conserved gene cluster. Many genes in this cluster have not been functionally characterized and would be promising candidates for future studies to elucidate V-nitrogenase function and regulation.
Maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes

Abstract Objective: To investigate maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes (PPROM) and to compare with pregnancies delivered at term. Materials and methods: In this cross-sectional study, 40 women with singleton pregnancies complicated with PPROM between 24 and 34 weeks of gestation were compared with gestational age-matched 40 pregnant women with no obstetrics complications, who delivered at term. The maternal serum galectin-1 and galectin-3 levels were measured. Results: Patients complicated with PPROM had significantly higher levels of galectin-1 (p = .001) and galectin-3 (p = .003) than the control group. Maternal serum galectin-3 levels were found significantly negatively correlated with the gestational age at delivery and birth weight. Conclusion: Maternal serum galectin-1 and galectin-3 levels were significantly higher in pregnancies complicated with PPROM. Galectin-1 and galectin-3, with their regulatory effects in key biological processes, may be both an initiating factor in the pathophysiology of PPROM, a marker in the prediction, and a target of preventing strategies of PPROM.
Neuroimaging markers of clinical progression in chronic inflammatory demyelinating polyradiculoneuropathy

Background: One of the main goals of novel, noninvasive imaging techniques like high-resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) is the prediction of treatment response for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: A total of 17 patients with CIDP were examined prospectively at baseline and every 9 months over a period of 18 months using CCM to quantify corneal nerve degeneration markers and immune cell infiltration as well as HRUS to detect changes of the cross-sectional area (CSA) of the peripheral nerves. Additionally, skin biopsy of the distal and proximal leg as well as quantitative sensory testing were performed at the first follow-up visit. Results: A value of more than 30 total corneal cells/mm2 in CCM at baseline identified patients with clinical progression with a sensitivity/specificity of 100% in our cohort. Corneal nerve fiber density and length remained low and stable over the study period and intra-epidermal fiber density was markedly reduced in the majority of the patients. Furthermore, an increase in Bochum ultrasound score (BUS), which summarizes the CSA of the ulnar nerve in Guyons’ canal, the ulnar nerve in the upper arm, the radial nerve in the spiral groove and the sural nerve between the gastrocnemius muscle, and a maximum BUS of 4 at study initiation identified patients with disease progression (sensitivity 80%, specificity 88%). Conclusions: BUS and corneal total cell infiltration seem to represent early markers for clinical progression in CIDP, thus having the potential to identify at-risk patients and impact treatment decisions.
Development of two antigen-binding fragments to a conserved linear epitope of human adenovirus and their application in immunofluorescence

Detection of human adenoviruses (HAdVs) in nasopharyngeal swab samples by immunofluorescence assay (IFA) will be valuable for diagnosing HAdV infection, which is a leading cause of severe respiratory tract disease, and will help in curbing the spread of HAdV. Monoclonal antibodies employed in IFA for HAdV detection should ideally target highly conserved epitope types. Here, we describe the development of two antigen-binding fragments (Fabs) with specific reactivity to HAdV using phage antibody library technology. When tested with IFA, both Fabs recognized cells infected with several types of HAdV, some of which have been identified in epidemics globally, or associated with outbreaks of severe or fatal acute respiratory diseases. The specificity and cross-reactivity of both Fabs to HAdVs indicated that the generated Fabs could be applied in the development of IFAs to detect HAdVs. Both Fabs bound to the knob proteins, as shown by chemiluminescence enzyme immunoassay and western blot. In addition, epitope mapping showed that both Fabs recognized a conserved linear epitope among several types of HAdV. Two different Fabs recognized the same epitope, suggesting that the epitope triggered the production of at least two kinds of antibodies in the body. The generated Fabs exerted no neutralization against HAdVs. The results demonstrate that both Fabs bind to an epitope that plays no role in neutralization of HAdV.
Ledipasvir and Sofosbuvir for Acute Hepatitis C Virus Monoinfection Associated with a High Risk of Acute Liver Failure

A 72-year-old Japanese man was referred to our hospital with yellow discoloration of the sclera and liver dysfunction. He was diagnosed with acute hepatitis C virus (HCV) infection on the basis of HCV-RNA positivity and anti-HCV seroconversion. A transjugular liver biopsy confirmed submassive hepatic necrosis. Five days after admission, no flapping tremor was observed, and the prothrombin time-international normalized ratio (PT-INR) and total bilirubin level showed increases of 1.70 and 17.8 mg/dL, respectively. The Model for End-Stage Liver Disease score was determined to be 25, and the risk of acute liver failure (ALF) was estimated to be 48% according to the Japan Hepatic Encephalopathy Prediction Model. Considering that rapid HCV clearance and temporary suppression of the immune response would prevent ALF, we prescribed oral ledipasvir (LDV) 90 mg and sofosbuvir (SOF) 400 mg for 12 weeks and intravenously injected methylprednisolone 1 g for 3 days. His PT-INR promptly improved, although the total bilirubin level increased to 30.3 mg/dL. Plasma bilirubin absorption was performed three times, and the total bilirubin level gradually decreased. HCV-RNA was still detectable at six weeks after the start of LDV/SOF therapy and finally undetectable at eight weeks. There were no adverse events associated with LDV/SOF. The patient was discharged 73 days after admission. A sustained virological response was achieved at 12 and 24 weeks after treatment. The findings from this case suggest that LDV/SOF therapy can be a promising option for acute HCV monoinfection associated with a high risk of ALF.
Suboptimal RNA–RNA interaction limits U1 snRNP inhibition of canonical mRNA 3’ processing

ABSTRACT It is increasingly appreciated that U1 snRNP transcriptomically suppresses the usage of intronic polyadenylation site (PAS) of mRNAs, an outstanding question is why frequently used PASs are not suppressed. Here we found that U1 snRNP could be transiently associated with sequences upstream of actionable PASs in human cells, and RNA–RNA interaction might contribute to the association. By focusing on individual PAS, we showed that the stable assembly of U1 snRNP near PAS might be generally required for U1 inhibition of mRNA 3ʹ processing. Therefore, actionable PASs that often lack optimal U1 snRNP docking site nearby is free from U1 inhibitory effect. Consistently, natural 5ʹ splicing site (5ʹ-SS) is moderately enriched ~250 nt upstream of intronic PASs whose usage is sensitive to functional knockdown of U1 snRNA. Collectively, our results provided an insight into how U1 snRNP selectively inhibits the usage of PASs in a cellular context, and supported a prevailing model that U1 snRNP scans pre-mRNA through RNA–RNA interaction to find a stable interaction site to exercise its function in pre-mRNA processing, including repressing the usage of cryptic PASs.
Upregulation of ATG7 attenuates motor neuron dysfunction associated with depletion of TARDBP/TDP-43

ABSTRACT A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patients with ALS and FTD, suggesting that its nuclear depletion contributes to neurodegeneration. However, the critical pathways impacted by the failure to repress cryptic exons that may contribute to neurodegeneration remain undefined. Here, we report that transcriptome analysis of TARDBP-deficient neurons revealed downregulation of ATG7, a critical gene required for macroautophagy/autophagy. Mouse and Drosophila models lacking TARDBP/TBPH in motor neurons exhibiting age-dependent neurodegeneration and motor deficits showed reduction of ATG7 and accumulation of SQSTM1/p62 inclusions. Importantly, genetic upregulation of the autophagy pathway improved motor function and survival in TBPH-deficient flies. Together with our observation that ATG7 is reduced in ALS-FTD brain tissues, these findings identify the autophagy pathway as one key effector of nuclear depletion of TARDBP that contributes to neurodegeneration. We thus suggest that the autophagy pathway is a therapeutic target for ALS-FTD and other disorders exhibiting TARDBP pathology. Abbreviations: ALS: amyotrophic lateral sclerosis; ANOVA: analysis of variance; ChAT: choline acetyltransferase; CTSD: cathepsin D; FTD: frontotemporal dementia; LAMP1: lysosomal associated membrane protein 1; NMJ: neuromuscular junction; RBFOX3/NeuN: RNA binding fox-1 homolog 3; SQSTM1: sequestosome 1; TARDBP/TDP-43: TAR DNA binding protein 43.
Wayfinding and acquisition of spatial knowledge with navigation assistance.

Integrated visualizations for assisted navigation were investigated that support both wayfinding and spatial learning. Participants navigated a predefined route with assistance through a virtual environment, visiting five target locations. Wayfinding accuracy was assessed. After wayfinding, self-to-object knowledge was measured with pointing tasks, and object-to-object knowledge was measured with an allocentric configurational task. Self-to-object knowledge was supported through self-to-targets-visualizations that provided information about the egocentric straight-line directions between the navigator and target locations. Both the acquisition of object-to-object knowledge as well as self-to-object knowledge was supported through comprehensive map visualizations. Alignment (rotations of the visualization according to changes of heading in the environment) appeared supportive for the acquisition of self-to-object knowledge with self-to-targets visualizations. Alignment was not effective with comprehensive maps. Wayfinding was impeded if visualizations were not aligned with the current heading. Individual differences in perspective taking ability played a strong role for wayfinding accuracy with misaligned visualizations. It is concluded that visualizations are encoded egocentrically for wayfinding purposes in the context of assisted navigation. Accordingly, the acquisition of self-to-object spatial knowledge can be supported through appropriate visualizations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Cost Effectiveness of Multigene Panel Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE Compared with single-marker genetic testing (SMGT), multigene panel sequencing (MGPS) has the potential to identify more patients with cancer who could benefit from targeted therapies, but the effects on outcome and total cost of care are uncertain. Our goal was to estimate the clinical and cost effectiveness of MGPS versus SMGT among patients with advanced non-small-cell lung cancer (aNSCLC). METHODS Patients with aNSCLC-stage IIIB or metastatic-who were diagnosed between 2011 and 2016 were identified from the Flatiron Health database. After stratifying patients into MGPS or SMGT cohorts, we analyzed the percentage of patients who received targeted treatment, survival, and total costs of care. SMGT included epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase testing. MGPS also allowed for the detection of BRAF, RET, ROS1, HER2, and MET mutations. Cost data sources were the Centers for Medicare & Medicaid Services Fee Schedule and 2017 average sales price drug cost. We estimated the incremental cost-effectiveness ratio from a US payer perspective over a lifetime horizon using a decision model. RESULTS We identified 5,688 patients with aNSCLC who received MGPS (n = 875) or SMGT (n = 4,813), of which 22% tested positive for epidermal growth factor receptor (18.5% MGPS; 17.3% SMGT) or anaplastic lymphoma kinase (3.59% MGPS; 3.78% SMGT). Among MGPS-tested patients, an additional 8% were found to have BRAF, RET, ROS1, HER2, or MET mutations. Of MGPS-tested patients, 21% received treatments that were targeted to the specific mutations versus 19% with SMGT. Expected survival was 1.14 life years (LYs) in SMGT versus 1.20 LYs in MGPS. Lifetime total costs were $8,814 higher per patient for MGPS. The incremental cost-effectiveness ratio of MGPS versus SMGT was $148,478 per LY gained. CONCLUSION On the basis of data from a nationwide oncology patient database, MGPS is shown to have moderate cost effectiveness compared with SMGT in patients with aNSCLC.
The effects of ambient particulate matter on human adipose tissue

ABSTRACT The effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM2.5 (PM <2.5 μm in diameter) and PM10 (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM10. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM10 and PM2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses.
Virtual Bokeh Reconstruction from a Single System of Lenses

We propose a method of virtual bokeh reconstruction by using only multiple differently-focused images acquired with a single system of lenses. First, we analyzed our previously proposed 3-D blurring filter that combines scene information and the acquired multiple differently-focused images to decompose the filter into ray-sets, each of which goes through a certain point on the lens. A new 2-D filter based on dimension reduction was then designed to allow the ray-sets to be reconstructed without the need to estimate the scene. A weighted composition of them provides free shapes of bokeh, i.e., the desired features of lenses and irises. Virtual bokeh reconstruction was simulated by utilizing synthetic multiple differently-focused images with a number of shapes of bokeh. The criteria for appropriate bokeh for image acquisition were also clarified. Finally, we show experimental results of virtual bokeh reconstruction from real images.
Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis

This study reports an unexpected role of late endosome–lysosome fusion in early endosome-to-Golgi trafficking of Shiga toxins and identifies tamoxifen to be a potent inhibitor of Shiga toxicosis. Shiga toxin 1 (STx1) and 2 (STx2), produced by Shiga toxin–producing Escherichia coli, cause lethal untreatable disease. The toxins invade cells via retrograde trafficking. Direct early endosome-to-Golgi transport allows the toxins to evade degradative late endosomes. Blocking toxin trafficking, particularly at the early endosome-to-Golgi step, is appealing, but transport mechanisms of the more disease-relevant STx2 are unclear. Using data from a genome-wide siRNA screen, we discovered that disruption of the fusion of late endosomes, but not autophagosomes, with lysosomes blocked the early endosome-to-Golgi transport of STx2. A subsequent screen of clinically approved lysosome-targeting drugs identified tamoxifen (TAM) to be a potent inhibitor of the trafficking and toxicity of STx1 and STx2 in cells. The protective effect was independent of estrogen receptors but dependent on the weak base property of TAM, which allowed TAM to increase endolysosomal pH and alter endosomal dynamics. Importantly, TAM treatment enhanced survival of mice injected with a lethal dose of STx1 or STx2. Thus, it may be possible to repurpose TAM for treating Shiga toxin–producing E. coli infections.
Relation between cognitive restraint and weight: Does a content validity problem lead to a wrong axis of care?

The aim of this research is to examine the relation between weight and cognitive restraint (CR), which is the intention to control food intake in order to maintain or lose weight, in a general French population sample. Is CR more prevalent in individuals with obesity than overweight, underweight or normal‐weight subjects in this cross‐sectional study? Are people affected by obesity non‐restrained eaters? A total of 507 French people (80.2% women and 19.8% men), aged 18‐78 years, responded to an online questionnaire. It appears that the most used questionnaire measuring CR has content validity problems as it seems to measure effective control and not the intention. Therefore, a numeric scale was used to answer the questions. Even if it is not possible in this study to test a causal link with latent variable modelling, our results seem to show that people with obesity more frequently intend to eat less or to eat healthier and/or to eat less sugar and fat than other people in order to control their weight. However, people affected by obesity do not succeed in so doing. These results raise the question of treatments advocating the increase of self‐control. Finally, it would be necessary to obtain a real, scientific consensus on what CR is and on how to measure it in order to study the most effective treatments for people with overweight or obesity.
Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype- bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors

Administration of azobenzenearsonate (ABA)-coupled syngeneic spleen cells intravenously to A/J mice leads to the generation of suppressor T cells (Ts1) which exhibit specific binding to ABA-bovine serum albumin (BSA)-coated dishes. These Ts1 share idiotypic determinants with the major cross-reactive idiotype (CRI) of the anti-ABA antibodies of A/J mice, and also produce a soluble suppressor factor (TsF) bearing CRI and I-J subregion-coded determinants. Injection of this TsF into naive A/J mice elicits a second set of specific suppressor cells (Ts2) which are not lysed by anti-CRI antibody plus C, and which do not bind to ABA- BSA-coated dishes. However, in contrast with Ts1, these Ts2 do bind to plates bearing CRI+ anti-ABA immunoglobulin. Thus, Ts2 exhibit anti- idiotypic specificity. These data indicate that antigen elicits the production of a soluble T cell product bearing both variable portion of the Ig heavy chain (VH) and I-J subregion-coded determinants which serves to communicate between T cell subsets to establish an idiotype- anti-idiotype regulatory pathway.