Miracle-dz/UniFAR-FTUs huggingface dataset:
Disagreement and Uncertainty Among Experts About how to Respond to Marijuana Use in Patients on Long-term Opioids for Chronic Pain: Results of a Delphi Study.

BACKGROUND Marijuana use is common among patients on long-term opioid therapy (LTOT) for chronic pain, but there is a lack of evidence to guide clinicians' response. OBJECTIVE To generate expert consensus about responding to marijuana use among patients on LTOT. DESIGN Analysis from an online Delphi study. SETTING/SUBJECTS Clinician experts in pain and opioid management across the United States. METHODS Participants generated management strategies in response to marijuana use without distinction between medical and nonmedical use, then rated the importance of each management strategy from 1 (not at all important) to 9 (extremely important). A priori rules for consensus were established, and disagreement was explored using cases. Thematic analysis of free-text responses examined factors that influenced participants' decision-making. RESULTS Of 42 participants, 64% were internal medicine physicians. There was consensus that it is not important to taper opioids as an initial response to marijuana use. There was disagreement about the importance of tapering opioids if there is a pattern of repeated marijuana use without clinical suspicion for a cannabis use disorder (CUD) and consensus that tapering is of uncertain importance if there is suspicion for CUD. Three themes influenced experts' perceptions of the importance of tapering: 1) benefits and harms of marijuana for the individual patient, 2) a spectrum of belief about the overall riskiness of marijuana use, and 3) variable state laws or practice policies. CONCLUSIONS Experts disagree and are uncertain about the importance of opioid tapering for patients with marijuana use. Experts were influenced by patient factors, provider beliefs, and marijuana policy, highlighting the need for further research.
Complications of Insufficient Dura and Blood Loss During Surgical Intervention in Shprintzen-Goldberg Syndrome: A Case Report

Patient: Female, 9 Final Diagnosis: Mandibular hypoplasia secondary to Shprintzen-Goldberg Syndrome Symptoms: Difficulty swallowing Medication: — Clinical Procedure: Bilateral mandibular osteotomy and distraction for mandibular hypolasia Specialty: Neurosurgery Objective: Rare disease Background: Shprintzen-Goldberg syndrome (SGS) is an extremely rare collagenopathy, most often caused by autosomal-dominant mutations in the SKI proto-oncogene, which is a component of the transforming growth factor beta (TGF-β) signaling pathway. Approximately 50–60 cases of SGS have been recorded in the literature worldwide since its discovery in 1982. This collagen disorder affects bone and vascular development throughout the body, resulting in craniosynostosis, scoliosis, chest deformities, and aortic root dilation. Patients may have problems in the central nervous system, including Chiari 1 malformation, hydrocephalus, and dilation of the lateral ventricles. Unfortunately, the symptoms of SGS closely parallel those of related collagenopathies involving mutations in the TGF-β signaling pathway, which makes accurate diagnosis difficult without genetic testing, especially in cases with complex presentation. Case Report: In this report we present the unique and complex disease manifestations in a 9-year-old girl with SGS. The patient had severe cervical spinal instability that resolved after surgical occipital-C4 fusion with an autograft from the rib. Midface distraction surgery was used to treat the patient’s craniosynostosis and related facial deformities. This surgery was complicated by loss of 750 mL of blood due to insufficient dura and prominent vasculature. Conclusions: Connective tissue symptoms associated with SGS can involve dural and vascular problems, as seen in this case report. Thus, the risk of extreme blood loss should be anticipated any time midface distraction surgery is performed on an SGS patient. Continued research is needed to define how this case relates to the SGS patient population.
Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < −2 SD) and 50 control (LAZ ≥ −2 SD) children, aged 12–18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin–adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin–adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin–adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.
The N-terminal region of RTP1S plays important roles in dimer formation and odorant receptor-trafficking

Receptor-transporting protein 1S (RTP1S) is an accessory protein that mediates the transport of mammalian odorant receptors (ORs) into the plasma membrane. Although most ORs fail to localize to the cell surface when expressed alone in nonolfactory cells, functional expression of ORs is achieved with the coexpression of RTP1S. However, the mechanism for RTP1S-mediated OR trafficking remains unclear. In this study, we attempted to reveal the mode of action and critical residues of RTP1S in OR trafficking. Experiments using N-terminal truncation and Ala substitution mutants of RTP1S demonstrated that four N-terminal amino acids have essential roles in OR trafficking. Additionally, using recombinant proteins and split luciferase assays in mammalian cells, we provided evidence for the dimer formation of RTP1S. Furthermore, we determined that the 2nd Cys residue is required for the efficient dimerization of RTP1S. Altogether, these findings provide insights into the mechanism for plasma membrane transport of ORs by RTP1S.
Rates of Molecular Evolution in a Marine Synechococcus Phage Lineage

Cyanophages are characterized by vast genomic diversity and the formation of stable ecotypes over time. The evolution of phage diversity includes vertical processes, such as mutation, and horizontal processes, such as recombination and gene transfer. Here, we study the contribution of vertical and horizontal processes to short-term evolution of marine cyanophages. Analyzing time series data of Synechococcus-infecting Myoviridae ecotypes spanning up to 17 years, we found a high contribution of recombination relative to mutation (r/m) in all ecotypes. Additionally, we found a molecular clock of substitution and recombination in one ecotype, RIM8. The estimated RIM8 evolutionary rates are 2.2 genome-wide substitutions per year (1.275 × 10−5 substitutions/site/year) and 29 genome-wide nucleotide alterations due to recombination per year. We found 26 variable protein families, of which only two families have a predicted functional annotation, suggesting that they are auxiliary metabolic genes with bacterial homologs. A comparison of our rate estimates to other phage evolutionary rate estimates in the literature reveals a negative correlation of phage substitution rates with their genome size. A comparison to evolutionary rates in bacterial organisms further shows that phages have high rates of mutation and recombination compared to their bacterial hosts. We conclude that the increased recombination rate in phages likely contributes to their vast genomic diversity.
Prenatal and Childhood Traffic-Related Air Pollution Exposure and Telomere Length in European Children: The HELIX Project

Background: Telomere length is a molecular marker of biological aging. Objective: Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age. Methods: In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) (n=1,396), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide (NO2), particulate matter with aerodynamic diameter ≤2. 5μm (PM2.5), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates. Results: LTL was inversely associated with prenatal and 1-y childhood NO2 and PM2.5 exposures levels. Each standard deviation (SD) increase in prenatal NO2 was associated with a −1.5% (95% CI: −2.8, −0.2) change in LTL. Prenatal PM2.5 was nonsignificantly associated with LTL (−0.7% per SD increase; 95% CI: −2.0, 0.6). For each SD increment in 1-y childhood NO2 and PM2.5 exposure, LTL shortened by −1.6% (95% CI: −2.9, −0.4) and −1.4% (95% CI: −2.9, 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL. Conclusion: Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148
Core services of intensive case management for people with mental illness: A network analysis

Background: In intensive case management (ICM), users receive a wide variety of services of varying content, which makes it difficult to understand the global features of ICM programs. Aims: The aim of this study was to examine the features of ICM programs using network analysis. Methods: A total of 233 ICM users in two Japanese medical institutions were recruited to participate. All received services were recorded for 2 months. In the network analysis, nodes represented types of ICM services and edges between two nodes depicted when over 5% of participants received both types of services. Results: We found high centrality values for ‘H5. Hospital-based counseling’, ‘O13. Outreach support for mental health medications’, ‘H13. Hospital-based support for mental health medication’, ‘T5. Counseling via telecommunication’, ‘H3. Hospital-based coordination of services in the medical institution’ and ‘T2. Coordination of services with other institutions via telecommunication’. These results indicated that these services were associated with various other types of services. Social functioning was related to ‘O13. Outreach support for mental health medication’, whereas need for ICM was related to ‘H13. Hospital-based support for mental health medications’, ‘T5. Counseling via telecommunication’ and ‘T2. Coordination of services with other institutions via telecommunication’ Conclusion: Based on these findings, we speculated that there are at least five types of core services in ICM: regular face-to-face contact, outreach services, hospital-based services, easy contacts and coordination. These findings clarified the features of ICM programs, which may help improve the understanding of case managers’ practice.
Comparison of dysregulated long noncoding RNAs in lung adenocarcinoma and spinal metastasis: A genome-wide analysis.

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer metastasis, yet the lncRNAs landscape of lung adenocarcinoma has not been completely characterized. The aim of this study was to assess the expression profile and potential function of lncRNA in lung adenocarcinoma and in spinal metastasis (SM). A genome-wide microarray analysis was conducted of lung adenocarcinoma and SM tissue from ten Chinese patients. A total of 3345 differentially expressed lncRNAs were detected. Of those, 761 lncRNAs were upregulated and 2584 were downregulated (fold-change > 2.0, P < 0.05). These differentially expressed lncRNAs were not evenly distributed among the chromosomes of human genome. Volcano plots of these differentially expressed lncRNAs revealed large variability in lncRNAs expression among 12 patients, indicating that certain lncRNAs may play a positive role in SM of lung adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated biological pathways that affect cell adhesion and the interaction of cytokines and cytokine receptors. Co-expression network analysis showed that 9458 lncRNAs had verified cis- and trans- target genes. All 2317 cis targeted genes were confirmed to be differentially expressed and influenced by dysregulated lncRNAs in SM of lung adenocarcinoma. Ten markedly dysregulated lncRNAs were verified randomly from the co-expression network. In conclusion, this study was a genome-wide survey of dysregulated lncRNAs and corresponding mRNAs that comprise co-regulation networks for SM and lung adenocarcinoma tissues. These dysregulated lncRNAs and mRNA networks could be used as therapeutic gene targets to prevent SM of lung adenocarcinoma and to predictively evaluate treatment efficacy.
Trehalose‐6‐phosphate signaling regulates thermoresponsive hypocotyl growth in Arabidopsis thaliana

Growth plasticity is a key mechanism by which plants adapt to the ever‐changing environmental conditions. Since growth is a high‐energy‐demanding and irreversible process, it is expected to be regulated by the integration of endogenous energy status as well as environmental conditions. Here, we show that trehalose‐6‐phosphate (T6P) functions as a sugar signaling molecule that coordinates thermoresponsive hypocotyl growth with endogenous sugar availability. We found that the loss of T6P SYNTHASE 1 (TPS1) in Arabidopsis thaliana impaired high‐temperature‐mediated hypocotyl growth. Consistently, the activity of PIF4, a transcription factor that positively regulates hypocotyl growth, was compromised in the tps1 mutant. We further show that, in the tps1 mutant, a sugar signaling kinase KIN10 directly phosphorylates and destabilizes PIF4. T6P inhibits KIN10 activity in a GRIK‐dependent manner, allowing PIF4 to promote hypocotyl growth at high temperatures. Together, our results demonstrate that T6P determines thermoresponsive growth through the KIN10‐PIF4 signaling module. Such regulation of PIF4 by T6P integrates the temperature‐signaling pathway with the endogenous sugar status, thus optimizing plant growth response to environmental stresses.
The Rel stringent factor from Thermus thermophilus: crystallization and X-ray analysis.

The stringent response, controlled by (p)ppGpp, enables bacteria to trigger a strong phenotypic resetting that is crucial to cope with adverse environmental changes and is required for stress survival and virulence. In the bacterial cell, (p)ppGpp levels are regulated by the concerted opposing activities of RSH (RelA/SpoT homologue) enzymes that can transfer a pyrophosphate group of ATP to the 3' position of GDP (or GTP) or remove the 3' pyrophosphate moiety from (p)ppGpp. Bifunctional Rel enzymes are notoriously difficult to crystallize owing to poor stability and a propensity for aggregation, usually leading to a loss of biological activity after purification. Here, the production, biochemical analysis and crystallization of the bifunctional catalytic region of the Rel stringent factor from Thermus thermophilus (RelTtNTD) in the resting state and bound to nucleotides are described. RelTt and RelTtNTD are monomers in solution that are stabilized by the binding of Mn2+ and mellitic acid. RelTtNTD crystallizes in space group P4122, with unit-cell parameters a = b = 88.4, c = 182.7 Å, at 4°C and in space group P41212, with unit-cell parameters a = b = 105.7, c = 241.4 Å, at 20°C.
Banking Meaning Representations from Treebanks

This paper describes a method to convert existing treebanks with syntactic information into banks of meaning representations. The central component is a system of evaluation for a small formal language with respect to an information state. Inputs to the evaluation system are for- mal language expressions obtained from the conversion of parsed representations conforming to (Penn Treebank Project) guidelines. Outputs from the evaluation system are Davidsonian (higher-order) predicate logic meaning representations. Having a system of evaluation as the basis for generating meaning representations makes possible accepting input with minimal conversion from existing treebanks and from the tools used to construct treebanks. Results of having built corresponding banks of meaning representations from available treebanks are discussed.
Reduced Trichomonas vaginalis viability in mice pretreated with parasite DNA

Abstract Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract leading to trichomoniasis, the most common sexually-transmitted non-viral disease worldwide. The immune response plays a critical role in the host defense against this parasite. Trichomonas' DNA contains unmethylated CpG motifs (CpGDNA) that in other microorganisms act as modulators of the immune response. However, the molecular mechanisms responsible for CpGDNA immune modulation are still unclear. As macrophages participate in the first line of defense against infection, we investigated the type of immune response of murine macrophages to T. vaginalis DNA (TvDNA). We observed high expression of the proinflammatory cytokines IL-6 and IL-12p40 in macrophages stimulated with TvDNA. In contrast, the anti-inflammatory response, assessed by IL-10 and IL-13 mRNA expression was delayed. This suggests that the immune response induced by TvDNA is modulated through cytokine production, mediated partly by NADPH-oxidase activity, as TvDNA induced reactive species of oxygen production and a rounded morphology in macrophages indicative of an M1 phenotype. Furthermore, infected mice pretreated with TvDNA displayed persistent vulvar inflammation and decreased parasite viability consistent with higher proinflammatory cytokine levels during infection compared to untreated mice. Overall, our findings suggest that TvDNA pretreatment modulates the immune response favouring parasite elimination.
Crystal structure of the Schizosaccharomyces pombe U7BR E2-binding region in complex with Ubc7

A 1.7 Å resolution co-crystal structure of U7BR from Schizosaccharomyces pombe in complex with Ubc7 is reported. Structural comparisons and biochemistry suggest that U7BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.
Relationship between high dietary fat intake and Parkinson’s disease risk: a meta-analysis

Objective: To assess whether dietary fat intake influences Parkinson’s disease risk. Data Sources: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used: (“Paralysis agitans” OR “Parkinson disease” OR “Parkinson” OR “Parkinson’s” OR “Parkinson’s disease”) AND (“fat” OR “dietary fat” OR “dietary fat intake”). Data Selection: Included studies were those with both dietary fat intake and Parkinson’s disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. Outcome Measures: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson’s disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson’s disease risk. Results: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson’s disease (P = 0.000, odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.26–1.75); in contrast, high total fat intake was not associated with Parkinson’s disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91–1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88–1.20) reduced the risk of Parkinson’s disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97–1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92–1.29) both increased the risk of Parkinson’s disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73–1.05), α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72–1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75–1.06) were all linked with a trend toward reduced Parkinson’s disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91–1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96–1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94–1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87–1.18) intake was not associated with Parkinson’s disease. Conclusion: Dietary fat intake affects Parkinson’s disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson’s disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson’s disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson’s disease.