Miracle-dz/UniFAR-FTUs huggingface dataset:
Alcoholics Anonymous and other Mutual Help Organizations: Impact of a 45-Minute Didactic for Primary Care and Categorical Internal Medicine Residents

Background: Substance use disorders (SUDs) are highly prevalent among primary care patients. One evidence-based, cost-effective referral option is ubiquitous mutual help organizations (MHOs) such as Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and SMART Recovery; however, little is known about how to effectively increase trainee knowledge and confidence with these referrals. The primary aim of this study was to evaluate whether a single 45-minute combined lecture and role play–based didactic for primary care residents could enhance knowledge, improve attitudes, and bolster confidence in referring patients with addictions to community MHOs. Methods: The authors developed a 45-minute lecture and role play addressing the evidence for MHOs, their respective background/content, and how to make effective referrals. Participants were administered a brief survey of their MHO-related knowledge, attitudes, and confidence before and after the session to evaluate the didactic impact. Results: Participants were 55 primary care and categorical internal medicine residents divided among postgraduate year 1 (PGY1; 27.3%), PGY2 (38.2%), and PGY3 (34.5%). They had a mean age of 29 (SD = 2.62); 49% were female, 69% were Caucasian, and 78% reported some religious affiliation. Participants’ subjective knowledge about MHOs increased significantly (P < .001), as did their confidence in making referrals (P < .001). Changes in participants’ attitudes about the importance of MHOs in aiding successful addiction recovery approached significance (P = .058). The proportion of participants with correct responses to each of 4 knowledge-based questions increased substantially. Conclusions: Primary care and internal medicine residents reported variable baseline knowledge of MHOs and confidence in making referrals, both of which were improved in response to a 45-minute didactic. Role play may be a useful supplementary tool in enhancing residents’ knowledge and skill in treating patients with SUD.
Nucleosomes influence multiple steps during replication initiation

Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation. Origin licensing assays showed that local nucleosome positioning enhanced origin specificity and modulated helicase loading by influencing ORC DNA binding. Interestingly, SWI/SNF- and RSC-remodeled nucleosomes were permissive for origin licensing but showed reduced helicase activation. Specific CREs rescued replication of these templates if added prior to helicase activation, indicating a permissive chromatin state must be established during origin licensing to allow efficient origin activation. Our studies show nucleosomes directly modulate origin licensing and activation through distinct mechanisms and provide insights into the regulation of replication initiation by chromatin. DOI: http://dx.doi. org/10.7554/eLife.22512. 001
Buckling behavior of pipes in oil and gas wells

Based on the non-linear differential equations of buckled pipes, the buckling behavior of pipes in different wellbores has been analyzed. The relation between the deflection of buckled pipe and the loads on it has been given, and the critical loads for sinusoidal and helical buckling within different wellbores subjected to axial and torsional loads have been determined. Therefore, the profile of load increase during the post-buckling process and the bending moments in the buckled pipe can be determined. In addition, the effects of down-hole packer as fixed end on the helical buckling behavior of pipes have been investigated. These results can be applied to the related engineering design and construction.
The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction

Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75NTR) is involved in a diverse arrays of cellular responses, including neurite outgrowth, neurogenesis, and negative regulation of spine density, which are associated with various neurological disorders. In this study, male Sprague-Dawley (SD) rats received 10 Gy cranial irradiation. Then, we evaluated the expression of p75NTR in the hippocampus after cranial irradiation and explored its potential role in radiation-induced synaptic dysfunction and memory deficits. We found that the expression of p75NTR was significantly increased in the irradiated rat hippocampus. Knockdown of p75NTR by intrahippocampal infusion of AAV8-shp75 ameliorated dendritic spine abnormalities, and restored synapse-related protein levels, thus preventing memory deficits, likely through normalization the phosphor-AKT activity. Moreover, viral-mediated overexpression of p75NTR in the normal hippocampus reproduced learning and memory deficits. Overall, this study demonstrates that p75NTR is an important mediator of irradiation-induced cognitive deficits by regulating dendritic development and synapse structure.
T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer

T‐cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up‐regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8+ T cells and CD11b+CD33+ myeloid‐derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression. To determine the underlying mechanism of TIM3 in immune response during HNSCC progression, we utilized the Tgfbr1/Pten 2cKO HNSCC mouse model with TIM3 overexpression. Treatment with anti‐TIM3 monoclonal antibody effectively suppressed tumor growth through restoring effector T‐cell function by targeting CD4+TIM3+ cells and CD8+TIM3+ cells and decreasing MDSCs. Our findings demonstrate TIM3 expression in patients with HNSCC and suggest anti‐TIM3 immunotherapy as a novel therapeutic approach for effective treatment of HNSCC.
An Expanded View of Joint Attention: Skill, Engagement, and Language in Typical Development and Autism.

This study provides an expanded view of joint attention and its relation to expressive language development. A total of 144 toddlers (40 typically developing, 58 with autism spectrum disorder [ASD], 46 with developmental delay [DD]) participated at 24 and 31 months. Toddlers who screened positive for ASD risk, especially those subsequently diagnosed with ASD, had poorer joint attention skills, joint engagement during parent-toddler interaction, and expressive language. Findings highlight the dynamic relation between joint attention and language development. In the ASD and DD groups, joint engagement predicted later expressive vocabulary, significantly more than predictions based on joint attention skills. Joint engagement was most severely impacted when toddlers did not talk initially and improved markedly if they subsequently began to speak.
Knockdown of Rice MicroRNA166 Confers Drought Resistance by Causing Leaf Rolling and Altering Stem Xylem Development1

Knockdown of microRNA166 increases drought resistance in rice via decreased stem water conductivity and reduced leaf transpiration rates. MicroRNAs are 19- to 22-nucleotide small noncoding RNAs that have been implicated in abiotic stress responses. In this study, we found that knockdown of microRNA166, using the Short Tandem Target Mimic (STTM) system, resulted in morphological changes that confer drought resistance in rice (Oryza sativa). From a large-scale screen for miRNA knockdown lines in rice, we identified miR166 knockdown lines (STTM166); these plants exhibit a rolled-leaf phenotype, which is normally displayed by rice plants under drought stress. The leaves of STTM166 rice plants had smaller bulliform cells and abnormal sclerenchymatous cells, likely causing the rolled-leaf phenotype. The STTM166 plants had reduced stomatal conductance and showed decreased transpiration rates. The STTM166 lines also exhibited altered stem xylem and decreased hydraulic conductivity, likely due to the reduced diameter of the xylem vessels. Molecular analyses identified rice HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4), a member of HD-Zip III gene family, as a major target of miR166; moreover, rice plants overexpressing a miR166-resistant form of OsHB4 resembled the STTM166 plants, including leaf rolling and higher drought resistance. The genes downstream of miR166-OsHB4 consisted of polysaccharide synthesis-related genes that may contribute to cell wall formation and vascular development. Our results suggest that drought resistance in rice can be increased by manipulating miRNAs, which leads to developmental changes, such as leaf rolling and reduced diameter of the xylem, that mimic plants’ natural responses to water-deficit stress.
Long-Term Shrinkage of High-Performance Concrete, HPC

In this article an extensive experimental and numerical study of shrinkage in HPC is outlined. For this purpose cylinders of eight qualities of concrete were studied. Parallel studies of autogenous, carbonation and drying shrinkage, hydration, internal relative humidity and strength were carried out. Previous research in the field is summed up. Finally the article presents the mechanisms of shrinkage in HPC by modelling correlations to the composition of the concrete and the physical properties. The project was carried out between the years 1992 and 1996.
In Vitro Comparison of Contemporary Radiographic Imaging Techniques for the Measurement of Inter-radicular Width

Objective To assess the reliability of inter-radicular measurements taken using dental pantomograms (DPT), long cone periapical radiographs (LCPA) and cone bean computed tomography (CBCT). Materials/Methods A typodont simulating a hypodontia patient undergoing fixed appliance treatment was used. LCPAs, DPT, I-CAT and Accuitomo CBCT images were taken and the distances between the edentulous spans were measured at the midpoint of the roots and the cemento-enamel junctions (CEJ) of adjacent teeth. The results of each modality were compared to each other to the actual inter-radicular space. Results The DPT overestimated inter-radicular widths by 2 mm or more [mean: 2.48; 95% confidence interval (CI): −1.09 to 6.05 mm]. The LCPA overestimated the inter-radicular widths by 1.5 mm with a 95% CI of −0.095 to 4.03 mm. The mean differences between gold standard (model) and Accuitomo was 0.57 mm (95% CI: −0.37 to 1.51 mm) for the root mean and 0.22 mm (95% CI: −0.52 to 0.96 mm) for the CEJ. This was similar to the differences between the model and I-CAT where the inter-radicular root mean difference was 0.38 mm (95% CI: −0.38 to 1.14 mm) and the CEJ mean difference was 0.21 mm (95% CI: −0.50 to 0.92 mm). Conclusion The CBCT overestimated the root distance by 0.48 mm and the CEJ width by 0.22 mm, which is clinically irrelevant for implant placement. The DPT overestimated inter-radicular width by 2 mm and the LCPA by 1.5 mm and this difference may put roots of adjacent teeth at risk during implant placement.
Association between psychosomatic health symptoms and common mental illness in Ghanaian adolescents: Age and gender as potential moderators

Little is known about the role of age and gender in the association between psychosomatic symptoms and common mental illness in Ghanaian adolescents. This cross-sectional study examined age and gender as moderators between psychosomatic symptoms and common mental illness using data from a school-based survey (N = 770). Males reported higher psychosomatic symptoms and common mental illness, while younger adolescents reported higher common mental illness only. Psychosomatic symptoms were positively associated with common mental illness, but age and gender did not moderate this association. Interventions aimed at reducing the prevalence rate in psychosomatic symptoms are crucial in decreasing common mental illness in Ghanaian adolescents.
Global expression analysis of gene regulatory pathways during endocrine pancreatic development

To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate α, β andδ cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
Anti-Inflammatory Benefits of Antibiotics: Tylvalosin Induces Apoptosis of Porcine Neutrophils and Macrophages, Promotes Efferocytosis, and Inhibits Pro-Inflammatory CXCL-8, IL1α, and LTB4 Production, While Inducing the Release of Pro-Resolving Lipoxin A4 and Resolvin D1

Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the potential anti-inflammatory and pro-resolution benefits of tylvalosin, a recently developed broad-spectrum veterinary macrolide derived from tylosin. Recent findings indicate that tylvalosin may modulate inflammation by suppressing NF-κB activation. Neutrophils and monocyte-derived macrophages were isolated from fresh blood samples obtained from 12- to 22-week-old pigs. Leukocytes exposed to vehicle or to tylvalosin (0.1, 1.0, or 10 µg/mL; 0.096–9.6 µM) were assessed at various time points for apoptosis, necrosis, efferocytosis, and changes in the production of cytokines and lipid mediators. The findings indicate that tylvalosin increases porcine neutrophil and macrophage apoptosis in a concentration- and time-dependent manner, without altering levels of necrosis or reactive oxygen species production. Importantly, tylvalosin increased the release of pro-resolving Lipoxin A4 (LXA4) and Resolvin D1 (RvD1) while inhibiting the production of pro-inflammatory Leukotriene B4 (LTB4) in Ca2+ ionophore-stimulated porcine neutrophils. Tylvalosin increased neutrophil phospholipase C activity, an enzyme involved in releasing arachidonic acid from membrane stores. Tylvalosin also inhibited pro-inflammatory chemokine (C–X–C motif) ligand 8 (CXCL-8, also known as Interleukin-8) and interleukin-1 alpha (IL-1α) protein secretion in bacterial lipopolysaccharide-stimulated macrophages. Together, these data illustrate that tylvalosin has potent immunomodulatory effects in porcine leukocytes in addition to its antimicrobial properties.
Delft University of Technology Extraction of structural extracellular polymeric substances from aerobic granular sludge

To evaluate and develop methodologies for the extraction of gel-forming extracellular polymeric substances (EPS), EPS from aerobic granular sludge (AGS) was extracted using six different methods (centrifugation, sonication, ethylenediaminetetraacetic acid (EDTA), formamide with sodium hydroxide (NaOH), formaldehyde with NaOH and sodium carbonate (Na2CO3) with heat and constant mixing). AGS was collected from a pilot wastewater treatment reactor. The ionic gel-forming property of the extracted EPS of the six different extraction methods was tested with calcium ions (Ca). From the six extraction methods used, only the Na2CO3 extraction could solubilize the hydrogel matrix of AGS. The alginatelike extracellular polymers (ALE) recovered with this method formed ionic gel beads with Ca. The Ca-ALE beads were stable in EDTA, formamide with NaOH and formaldehyde with NaOH, indicating that ALE are one part of the structural polymers in EPS. It is recommended to use an extraction method that combines physical and chemical treatment to solubilize AGS and extract structural EPS.
Population trends in Vermivora warblers are linked to strong migratory connectivity

Significance Identifying drivers of population trends in migratory animals is difficult due to their reliance on different geographic regions throughout the annual cycle. Populations of Nearctic–Neotropical migratory birds are often thought to be limited by spatial variation in factors affecting reproduction and survival during the breeding season. We tracked individual songbirds from a two-species complex of New World warblers and discovered unequivocal evidence of a system in which strong associations between breeding areas and nonbreeding areas (i.e., migratory connectivity) is concordant with breeding population trends. The strong migratory connectivity we documented is associated with differential rates of land-use change in population-specific nonbreeding areas. Our results suggest that other migratory species with similar population trends may also exhibit strong migratory connectivity. Migratory species can experience limiting factors at different locations and during different periods of their annual cycle. In migratory birds, these factors may even occur in different hemispheres. Therefore, identifying the distribution of populations throughout their annual cycle (i.e., migratory connectivity) can reveal the complex ecological and evolutionary relationships that link species and ecosystems across the globe and illuminate where and how limiting factors influence population trends. A growing body of literature continues to identify species that exhibit weak connectivity wherein individuals from distinct breeding areas co-occur during the nonbreeding period. A detailed account of a broadly distributed species exhibiting strong migratory connectivity in which nonbreeding isolation of populations is associated with differential population trends remains undescribed. Here, we present a range-wide assessment of the nonbreeding distribution and migratory connectivity of two broadly dispersed Nearctic-Neotropical migratory songbirds. We used geolocators to track the movements of 70 Vermivora warblers from sites spanning their breeding distribution in eastern North America and identified links between breeding populations and nonbreeding areas. Unlike blue-winged warblers (Vermivora cyanoptera), breeding populations of golden-winged warblers (Vermivora chrysoptera) exhibited strong migratory connectivity, which was associated with historical trends in breeding populations: stable for populations that winter in Central America and declining for those that winter in northern South America.
Anti-Angiogenics: Current Situation and Future Perspectives

Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial growth factor (VEGF) is a key driver of sprouting angiogenesis, ii) VEGF is overexpressed in most solid cancers, and iii) inhibition of VEGF can suppress tumor growth in animal models. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve the tumor of nutrients and oxygen, primarily through the blockade of VEGF/VEGF receptor signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, either alone or in combination with chemotherapy and other targeted therapies. However, inhibition of VEGF signaling is not effective in all cancers, and anti-angiogenics have often only limited impact on overall survival of cancer patients. This review focuses on the current status of FDA-approved anti-angiogenic antibodies and tyrosine kinase inhibitors and summarizes the progress and future directions of VEGF-targeted therapy.
Environmentally relevant chemical mixtures of concern in waters of United States tributaries to the Great Lakes

The North American Great Lakes are a vital natural resource that provide fish and wildlife habitat, as well as drinking water and waste assimilation services for millions of people. Tributaries to the Great Lakes receive chemical inputs from various point and nonpoint sources, and thus are expected to have complex mixtures of chemicals. However, our understanding of the co‐occurrence of specific chemicals in complex mixtures is limited. To better understand the occurrence of specific chemical mixtures in the US Great Lakes Basin, surface water from 24 US tributaries to the Laurentian Great Lakes was collected and analyzed for diverse suites of organic chemicals, primarily focused on chemicals of concern (e.g., pharmaceuticals, personal care products, fragrances). A total of 181 samples and 21 chemical classes were assessed for mixture compositions. Basin wide, 1664 mixtures occurred in at least 25% of sites. The most complex mixtures identified comprised 9 chemical classes and occurred in 58% of sampled tributaries. Pharmaceuticals typically occurred in complex mixtures, reflecting pharmaceutical‐use patterns and wastewater facility outfall influences. Fewer mixtures were identified at lake or lake‐influenced sites than at riverine sites. As mixture complexity increased, the probability of a specific mixture occurring more often than by chance greatly increased, highlighting the importance of understanding source contributions to the environment. This empirically based analysis of mixture composition and occurrence may be used to focus future sampling efforts or mixture toxicity assessments. Integr Environ Assess Manag 2018;14:509–518. © 2018 SETAC