Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Functions of Bombyx mori Peptidoglycan Recognition Protein 2 in Immune Responses to Bacteria and Viruses

Peptidoglycan recognition protein (PGRP) is an important pattern recognition receptor in innate immunity that is vital for bacterial recognition and defense in insects. Few studies report the role of PGRP in viral infection. Here we cloned two forms of PGRP from the model lepidopteran Bombyx mori: BmPGRP2-1 is a transmembrane protein, whereas BmPGRP2-2 is an intracellular protein. BmPGRP2-1 bound to diaminopimelic acid (DAP)-type peptidoglycan (PGN) to activate the canonical immune deficiency (Imd) pathway. BmPGRP2-2 knockdown reduced B. mori nucleopolyhedrovirus (BmNPV) multiplication and mortality in cell lines and in silkworm larvae, while its overexpression increased viral replication. Transcriptome and quantitative PCR (qPCR) results confirmed that BmPGRP2 negatively regulated phosphatase and tensin homolog (PTEN). BmPGRP2-2 expression was induced by BmNPV, and the protein suppressed PTEN-phosphoinositide 3-kinase (PI3K)/Akt signaling to inhibit cell apoptosis, suggesting that BmNPV modulates BmPGRP2-2-PTEN-PI3K/Akt signaling to evade host antiviral defense. These results demonstrate that the two forms of BmPGRP2 have different functions in host responses to bacteria and viruses.
Using Etomidate and Midazolam for Screening Colonoscopies Results in More Stable Hemodynamic Responses in Patients of All Ages

Background/Aims Recent studies have demonstrated that etomidate is a safe sedative drug with noninferior sedative effects. In our recent study, we revealed that etomidate/midazolam was more hemodynamically stable than propofol/midazolam in elderly patients undergoing colonoscopies. We aimed to investigate whether compared with propofol/midazolam, etomidate/midazolam causes fewer cardiopulmonary adverse events with noninferior efficacy for screening colonoscopies in patients of all ages. Methods In this single-center, randomized, double-blind study, we prospectively enrolled 200 patients. The patients were divided into etomidate and propofol groups. The primary outcome was the occurrence of cardiopulmonary adverse events. The secondary outcomes were the proportion of patients with fluctuations in vital signs (oxygen desaturation and transient hypotension), adverse events interrupting the procedure, and sedation-related outcomes. Results Adverse cardiopulmonary events were more common in the propofol group than the etomidate group (65.0% vs 51.0%, respectively; p=0.045). Forty-six patients (46.0%) in the propofol group and 29 (29.0%) in the etomidate group experienced fluctuations in their vital signs (p=0.013). The proportions of patients experiencing adverse events that interrupted the procedure, including myoclonus, were not significantly different between the two groups (etomidate: 20.0% vs propofol: 11.0%; p=0.079). Both groups had similar sedation-related outcomes. Multivariate analysis revealed that compared with the propofol groups, the etomidate group had a significantly lower risk of fluctuations in vital signs (odds ratio, 0.427; 95% confidence interval, 0.230 to 0.792; p=0.007). Conclusions Compared with using propofol/midazolam, using etomidate/midazolam for screening colonoscopies results in more stable hemodynamic responses in patients of all ages; therefore, we recommend using etomidate/midazolam for colonoscopies in patients with cardiovascular risk factors.
The complement receptor C5aR2 promotes protein kinase R expression and contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages

The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a multimeric protein complex that mediates maturation of the cytokines IL-1β and IL-18 as well as release of the proinflammatory protein high-mobility group box 1 (HMGB1) and contributes to several inflammatory diseases, including sepsis, gout, and type 2 diabetes. In this context, the well-studied active complement fragment C5a and its receptor C5aR1 or C5aR2 orchestrate the inflammatory responses in many diseases. Although a C5a-C5aR interaction in NLRP3-associated diseases has been suggested, little is known about the details of C5a–C5aR cross-talk with the NLRP3 inflammasome in macrophages. In this study, using mice and murine macrophages and cytokines, immunoblotting, siRNA, and quantitative real-time PCR assays, we demonstrate that C5aR2 deficiency restricts activation of the NLRP3 inflammasome and release of HMGB1 both in vitro and in vivo. Mechanistically, we found that C5aR2 promotes NLRP3 activation by amplifying dsRNA-dependent PKR expression, which is an important NLRP3-activating factor. We also observed that elevation of PKR expression because of the C5a–C5aR2 interaction depends on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase pathway and type I IFN signaling. In conclusion, these findings reveal that C5aR2 contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages.
The Use of Relations and Functions Games Based on Balanced Design in Mathematics Subjects to Improve Student Learning Outcomes

Game Relations and Functions are digital game-based learning in junior high school mathematics subjects. In this study will discuss how to use the game Relationships and Functions that have been designed using the Balanced Design method. The research method used was a quasi-experiment with the One group Pretest Post-test design. A total of 40 junior high school students were involved in this study to determine differences in student learning outcomes in the cognitive domain before and after using the Relationship and Function games. The instrument used is a type of multiple choice objective test of 20 questions with details of 8 questions related to relations material and 12 questions related to functions material. The results showed that there were differences in the improvement of student learning outcomes before and after using the game Relations and Functions in Mathematics subjects.
Mining Implicit Treatment Concepts for Neural Precision Medicine

Precision medicine (PM) is regarded as an information retrieval (IR) task in which biomedical articles containing treatment information about specific diseases or genetic variants are retrieved in response to patient record for the purpose of providing medical evidence to the point-of-care. In existing PM approaches, manual keywords, such as “treatment” and “therapy,” are considered direct indicators of treatment information and are thereby introduced to expand the original query. However, the common medical concepts that are implicitly related to treatment (such as “oncogene” and “tumor”), and differ the relevant documents from the non-relevant ones, are yet to be utilized. To bridge the gap, in this paper, we propose an extension of the state-of-the-art neural IR (NIR) models, including K-NRM and DRMM, to encapsulate the PM solutions within a neural network framework, referred to as NIR $^{PM}$ . Specifically, the proposed approach mines a global list of common medical concepts from documents that are judged pertinent to different queries. Thereafter, the mined implicit concepts are incorporated within an NIR framework to enhance the effectiveness of PM. The experimental results on the standard Text REtrieval Conference (TREC) PM track benchmark confirm the superior performance of the proposed NIRPM model.
Understanding and Addressing CLSI Breakpoint Revisions: a Primer for Clinical Laboratories

The Clinical and Laboratory Standards Institute (CLSI) has revised several breakpoints since 2010 for bacteria that grow aerobically. In 2019, these revisions include changes to the ciprofloxacin and levofloxacin breakpoints for the Enterobacteriaceae and Pseudomonas aeruginosa, daptomycin breakpoints for Enterococcus spp. , and ceftaroline breakpoints for Staphylococcus aureus. ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) has revised several breakpoints since 2010 for bacteria that grow aerobically. In 2019, these revisions include changes to the ciprofloxacin and levofloxacin breakpoints for the Enterobacteriaceae and Pseudomonas aeruginosa, daptomycin breakpoints for Enterococcus spp. , and ceftaroline breakpoints for Staphylococcus aureus. Implementation of the revisions is a challenge for all laboratories, as not all systems have FDA clearance for the revised (current) breakpoints, compounded by the need for laboratories to perform validation studies and to make updates to laboratory information system/electronic medical record builds in the setting of limited information technology infrastructure. This minireview describes the breakpoint revisions in the M100 supplement since 2010 and strategies for the laboratory on how to best adopt these in clinical testing.
Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.
Why the whole is more than the sum of its parts: Salience-driven overestimation in aggregated tactile sensations

Experimental psychology often studies perception analytically, reducing its focus to minimal sensory units, such as thresholds or just noticeable differences in a single stimulus. Here, in contrast, we examine a synthetic aspect: how multiple inputs to a sensory system are aggregated into an overall percept. Participants in three experiments judged the total stimulus intensity for simultaneous electrical shocks to two digits. We tested whether the integration of component somatosensory stimuli into a total percept occurs automatically, or rather depends on the ability to consciously perceive discrepancy among components (Experiment 1), whether the discrepancy among these components influences sensitivity or/and perceptual bias in judging totals (Experiment 2), and whether the salience of each individual component stimulus affects perception of total intensity (Experiment 3). Perceptual aggregation of two simultaneous component events occurred both when participants could perceptually discriminate the two intensities, and also when they could not. Further, the actual discrepancy between the stimuli modulated both participants’ sensitivity and perceptual bias: increasing discrepancies produced a systematic and progressive overestimation of total intensity. The degree of this bias depended primarily on the salience of the stronger stimulus in the pair. Overall, our results suggest that important nonlinear mechanisms contribute to sensory aggregation. The mind aggregates component inputs into a coherent and synthetic perceptual experience in a salience-weighted fashion that is not based on simple summation of inputs.
The prevalence of frailty among acute stroke patients, and evaluation of method of assessment

Objective: We aimed to determine prevalence of pre-stroke frailty in acute stroke and describe validity of a Frailty Index–based assessment. Design: Cross-sectional. Setting: Single UK urban teaching hospital. Subjects: Consecutive acute stroke unit admissions, recruited in four waves (May 2016–August 2018). We performed the assessments within first week and attempted to include all admissions. Main measures: Our primary measure was a Frailty Index, based on cumulative disorders. A proportion of participants were also assessed with the ‘Frail non-disabled’ questionnaire. We evaluated concurrent validity of Frailty Index against variables associated with frailty in non-stroke populations. We described predictive validity of Frailty Index for stroke severity and delirium. We described convergent validity, quantifying agreement between frailty assessments and a measure of pre-stroke disability (modified Rankin Scale) using kappa statistics and correlations. Results: We included 546 patients. A Frailty Index–defined frailty syndrome was observed in 427 of 545 patients (78%), of whom, 151 (28%) had frank frailty and 276 (51%) were pre-frail. Phenotypic frailty was observed in 72 of 258 patients (28%). We demonstrated concurrent validity via significant associations with all variables (all p < 0.01). We demonstrated predictive validity for stroke severity and delirium (p < 0.01). Agreement between the frailty measures was poor (kappa = –0.06) and convergent validity was moderate (Frail non-disabled ‘Cramer’s V’ = 0.25; modified Rankin Scale ‘Cramer’s V’ = 0.47). Conclusion: Frailty is present in around one in four patients with acute stroke; if pre-frailty is included, then a frailty syndrome is seen in three out of four patients. The Frailty Index is a valid measure of frailty in stroke; however, there is little agreement between this scale and other measurements of frailty.
Evaluation of the ELITe InGenius PCR Platform for Detection of Mycoplasma pneumoniae

Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia in persons of all ages. Due to the fastidious nature of this bacterium and the necessary specialized growth media, nucleic acid amplification testing is currently the most reliable means for patient diagnostics. ABSTRACT Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia in persons of all ages. Due to the fastidious nature of this bacterium and the necessary specialized growth media, nucleic acid amplification testing is currently the most reliable means for patient diagnostics. Analytical sensitivity, specificity, reproducibility, and clinical performance of the ELITe InGenius automated PCR platform with its MGB Alert M. pneumoniae real-time PCR research use only reagents (ELITechGroup, Inc., Bothell, WA) were compared with those of a laboratory-developed real-time PCR assay targeting repMp1 for detection of M. pneumoniae. The ELITe InGenius PCR assay successfully detected 31 distinct M. pneumoniae clinical isolates and reference strains, and there was no cross-reactivity with other mollicutes, Gram-positive bacteria, or Gram-negative bacteria. In testing 223 clinical samples, the ELITe InGenius PCR showed 95.79% and 99.22% positive and negative agreement with the repMp1 assay, respectively. Additionally, the ELITech platform showed 98.91% positive and 96.95% negative predictive values, and there was no significant difference detected between the two assays (McNemar’s test, P = 0.375). The ELITe InGenius PCR assay limit of detection was 0.16 CFU/PCR test or 4.16 genome copies (GCs)/test. Accuracy, instrument ease-of-use, and decreased hands-on time make the ELITe InGenius platform suitable for detection of M. pneumoniae directly from clinical specimens.
Gcorn Plant: A Database for Retrieving Functional and Evolutionary Traits of Plant Genes1[OPEN]

The Gcorn plant database was designed for the retrieval of information on homology and evolution of a plant gene of interest based on 2, 682, 261 amino acid sequences of 73 species. Gene homology helps us understand gene function and speciation. The number of plant genes and species registered in public databanks is continuously increasing. It is useful to associate homologous genes of various plants to better understand plant speciation. We designed the Gcorn plant database for the retrieval of information on homology and evolution of a plant gene of interest. Amino acid sequences of 73 species (62 land plants and 11 green algae), containing 2,682,261 sequences, were obtained from the National Center for Biotechnology Information (NCBI) Reference Sequence database. Based on NCBI BLAST searches between these sequences, homologous genes were grouped at various thresholds of homology indices devised by the authors. To show functional and evolutionary traits of a gene of interest, a phylogenetic tree, connecting genes with high homology indices, and line charts of the numbers of genes with various homology indices, are depicted. In addition, such indices are projected on a network graph in which species studied are connected based on the ratios of homologous genes, and on a phylogenetic tree for species based on NCBI Taxonomy. Gcorn plant provides information on homologous genes at various virtual time points along with speciation in plants.
Obstructive Sleep Apnea in Adults.

This CPB has been revised to state that the following are considered experimental and investigational: (i) measurement of central corneal thickness, intra-ocular pressure, and retinal nerve fiber layer thickness for grading severities of obstructive sleep apnea syndrome (OSAS); (ii) measurement of Fas-positive lymphocytes for evaluation of systemic inflammation in OSAS; (iii) upper gastro-intestinal endoscopy for diagnosis of OSAS; and (iv) use of serum level of advanced glycation end-products as a biomarker of obstructive sleep apnea-hypopnea syndrome.
Antioxidant Activity, and Volatile and Phytosterol Contents of Strobilanthes crispus Dehydrated Using Conventional and Vacuum Microwave Drying Methods

The preservation of active constituents in fresh herbs is affected by drying methods. An effective drying method for Strobilanthes crispus which is increasingly marketed as an important herbal tea remains to be reported. This study evaluated the effects of conventional and new drying technologies, namely vacuum microwave drying methods, on the antioxidant activity and yield of essential oil volatiles and phytosterols. These drying methods included convective drying (CD) at 40 °C, 50 °C, and 60 °C; vacuum microwave drying (VMD) at 6, 9, and 12 W/g; convective pre-drying and vacuum microwave finish drying (CPD-VMFD) at 50 °C and 9 W/g; and freeze-drying (FD). GC–MS revealed 33 volatiles, and 2-hexen-1-ol, 2-hexenal, 1-octen-3-ol, linalool, and benzaldehyde were major constituents. The compounds β-sitosterol and α-linolenic acid were the most abundant phytosterol and fatty acid, respectively, in fresh S. crispus. The highest phenolic content was achieved with CD at 60 °C. The highest antioxidant activity was obtained with CD at 40 °C and VMD at 9 W/g. On the contrary, the highest total volatiles and phytosterols were detected with CD at 50 °C and VMD at 9 W/g, respectively. This study showed that CD and VMD were effective in producing highly bioactive S. crispus. A suitable drying parameter level, irrespective of the drying method used, was an important influencing factor.
Structural basis for auxiliary subunit KCTD16 regulation of the GABAB receptor

Significance Human GABAB receptor inhibits the activity of neurons in the brain. Malfunction of the receptor is associated with various neurological and mood disorders, including spasticity, epilepsy, addiction, and anxiety. GABAB receptor consists of principal and auxiliary subunits. The principal subunits form the receptor core that responds to neurotransmitters, while the auxiliary subunits modify the receptor output upon stimulation. The crystal structure of an auxiliary subunit bound to a peptide fragment of the principal subunit reveals their interaction and sheds light on the assembly of GABAB receptor signaling complex. Furthermore, the binding interface of GABAB receptor and KCTD presents a potential site for the design of compounds for regulating receptor function and treating GABAB-associated diseases. Metabotropic GABAB receptors mediate a significant fraction of inhibitory neurotransmission in the brain. Native GABAB receptor complexes contain the principal subunits GABAB1 and GABAB2, which form an obligate heterodimer, and auxiliary subunits, known as potassium channel tetramerization domain-containing proteins (KCTDs). KCTDs interact with GABAB receptors and modify the kinetics of GABAB receptor signaling. Little is known about the molecular mechanism governing the direct association and functional coupling of GABAB receptors with these auxiliary proteins. Here, we describe the high-resolution structure of the KCTD16 oligomerization domain in complex with part of the GABAB2 receptor. A single GABAB2 C-terminal peptide is bound to the interior of an open pentamer formed by the oligomerization domain of five KCTD16 subunits. Mutation of specific amino acids identified in the structure of the GABAB2–KCTD16 interface disrupted both the biochemical association and functional modulation of GABAB receptors and G protein-activated inwardly rectifying K+ channel (GIRK) channels. These interfacial residues are conserved among KCTDs, suggesting a common mode of KCTD interaction with GABAB receptors. Defining the binding interface of GABAB receptor and KCTD reveals a potential regulatory site for modulating GABAB-receptor function in the brain.
Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.