Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors that predict good Active Support in services for people with intellectual disabilities: A multilevel model

Abstract Background Active Support, now widely adopted by disability support organizations, is difficult to implement. The study aim was to identify the factors associated with good Active Support. Methods Data on service user and staff characteristics, quality of Active Support and practice leadership were collected from a sample of services from 14 organizations annually for between 2 and 7 years, using questionnaires, structured observations and interviews. Data were analysed using multilevel modelling (MLM). Results Predictors of good Active Support were adaptive behaviour, practice leadership, Active Support training, and time since its implementation. Heterogeneity, having more than six people in a service and larger organizations were associated with lower quality of Active Support. Conclusions In order to ensure that Active Support is consistently implemented, and thus, quality of life outcomes improved, organizations need to pay attention to both service design and support for staff through training and practice leadership.
NoiseFlow: Learning Optical Flow from Low SNR Cryo-EM Movie

Cryo-EM movie in single particle analysis has extremely low SNR and requires aligning multiple frames to achieve signal enhancement. Currently, signal processing technique is adopted to estimate the motion vector between a pair of cryo-EM movie frames at patch-level, and the estimated motion vector is used as the reference for frame alignment, whose accuracy will determine the resolution of the reconstructed 3D structure of the particle. The patch-level motion may not well represent the beam-induced motion of particles since particles in a patch move towards different directions due to beam striking. However, the low SNR of cryo-EM movie makes it difficult to estimate the motion of particles at pixel-level. Meanwhile, existing optical flow estimation models only consider the ideal case where high-quality videos are provided, which fail to obtain optical flow from cryo-EM movie. In this paper, we diminish this limitation by proposing a model called NoiseFlow, a deep learning network for optical flow estimation from low SNR cryo-EM movie. NoiseFlow makes use of the multi-frame stacking module and the denoising module to extract noise-invariant features, and then computes the correlation volume from noise-invariant features to learn optical flow. For evaluation, we train our model on two synthetic cryo-EM movie datasets and infer on real cryo-EM data. The experimental results illustrate that NoiseFlow achieves state-of-the-art performance on both synthetic and real cryo-EM datasets.
Adenoma miss rate of polypectomy-referring hospitals is high in Korea

Background/Aims We evaluated the miss rates of polyps, adenomas, and advanced neoplasia of polypectomy-referring hospitals and risk factors for missed adenomas. Methods We compared medical records and electronic images of initial colonoscopies from polypectomy-referring hospitals with those of corresponding therapeutic colonoscopies from Seoul St. Mary’s Hospital obtained from May 2014 to February 2016. Results A total of 147 patients (56.6 ± 12.1 years, 37 females) were included. The mean number of polyps and adenomas detected on initial colonoscopy was 2.4 ± 1.7 and 1.7 ± 1.4, respectively. The mean number of additionally detected polyps and adenomas per patient during therapeutic colonoscopy was 1.4 ± 1.8 and 1.0 ± 1.5, respectively. Pooled miss rate for polyps, adenomas, and advanced neoplasia was 36%, 37%, and 11%, respectively. Pooled miss rate for adenomas was significantly higher for right-sided, non-pedunculated, and small (< 1 cm) adenomas (p = 0.031, p = 0.000, and p = 0.000, respectively). The miss rate of polyps, adenomas, and advanced neoplasia per patient was 60%, 49%, and 7%, respectively. Multivariate analysis revealed age and number of adenoma on initial colonoscopy were significantly related with risk for adenoma-missing (p = 0.005 and p = 0.023, respectively). Conclusions Among patients referred for polypectomy, adenoma is missed in one of two patients and advanced neoplasm is missed in one of 13. Patients with advanced age or multiple adenoma on initial colonoscopy have a higher possibility of missed adenoma. Total colon exploration should be performed carefully during therapeutic colonoscopy.
Modulation of brain tumor risk by genetic SNPs in PARP1gene: Hospital based case control study

PARP-1 gene plays an essential part in base excision repair pathway and its functional variations result in several types of cancer. In this study we have explored the effect of genetic variations in PARP-1 gene in brain tumorigenesis. This case control study comprised of 500 brain tumor cases along with 500 healthy controls. Three polymorphisms of PARP-1 gene, rs1136410 (Val762Ala), rs1805404 (Asp81Asp) and rs1805414 (Ala284Ala) were analyzed using AS-PCR method followed by DNA sequencing. Joint effect model, haplotype analysis and linkage disequilibrium of these polymorphisms was assessed using Haploview 4.2. In rs1136410 (Val762Ala) heterozygous mutant genotype (CT) was observed notably lower (OR: 0.44., 95% CI: 0.33–0.57., p<0.0001) in brain tumor patients compared to controls and ~2 fold increased frequency of homozygous mutant genotype (CC) was observed in brain tumor patients versus controls (OR: 1.51., 95%CI: 1.16–1.96, p = 0.001). In rs1805414 (Ala284Ala), frequency of heterozygous mutant genotype (CT) was observed lower (OR: 0.77., 95% CI: 0.60–0.99., p = 0.05) in patients versus controls. In rs1805404 (Asp81Asp), heterozygous mutant genotyping (CT) was observed lower in brain tumor patients compared with the healthy controls (OR: 0.63., 95% CI: 0.48–0.83., p = 0.001). However, homozygous mutant genotype (TT) was observed increased in patients compared to controls (OR: 1.41., 95% CI:1.07–1.85., p = 0.01). We assessed the fact that in combination the PARP-1 gene SNPs, rs1136410 (Val762Ala), rs1805414 (Ala284Ala) and rs1805404 (Asp81Asp) may increase the brain pathogenesis at least in Pakistani population.
C4 and crassulacean acid metabolism within a single leaf: deciphering key components behind a rare photosynthetic adaptation.

Though biochemically related, C4 and crassulacean acid metabolism (CAM) systems are expected to be incompatible. However, Portulaca species, including P. oleracea, operate C4 and CAM within a single leaf, and the mechanisms behind this unique photosynthetic arrangement remain largely unknown. Here, we employed RNA-seq to identify candidate genes involved exclusively or shared by C4 or CAM, and provided an in-depth characterization of their transcript abundance patterns during the drought-induced photosynthetic transitions in P. oleracea. Data revealed fewer candidate CAM-specific genes than those recruited to function in C4 . The putative CAM-specific genes were predominantly involved in nighttime primary carboxylation reactions and malate movement across the tonoplast. Analysis of gene transcript-level regulation and photosynthetic physiology indicated that C4 and CAM co-exist within a single P. oleracea leaf under mild drought conditions. Developmental and environmental cues were shown to regulate CAM expression in stems, whereas the shift from C4 to C4 -CAM hybrid photosynthesis in leaves was strictly under environmental control. Moreover, efficient starch turnover was identified as part of the metabolic adjustments required for CAM operation in both organs. These findings provide insights into C4 /CAM connectivity and compatibility, contributing to a deeper understanding of alternative ways to engineer CAM into C4 crop species.
Reports of the benefits of drug use from individuals with substance use disorders

Abstract Background: The perceived benefits of drug use are not currently integrated into the treatment of substance use disorder. This omission appears paradoxical and is unsubstantiated by empirical research. As the perceived benefits of drug use are catalysts for drug initiation, relapse and continuous use, increased knowledge about these benefits seems crucial to efficacious treatment. Aims: To investigate the perceived benefits of drug use in substance use disorder. Method: The study is a phenomenological-hermeneutical investigation using thematic analysis of interviews with 30 long-term recovered adult service users. Results: Our thematic analysis resulted in three themes and several sub-themes: (1) Benefits of drug use; (2) Necessity of intense experiences; and (3) Importance of being unconventional. Conclusions: Findings indicate that the benefits of non-problematic and problematic drug use are motivated by similar individual and social needs. An absolute distinction between problematic and non-problematic drug use thus seems arbitrary and potentially counterproductive for clinical practice. The benefits of drug use should be researched as a possible add-on treatment module, as this knowledge may be of significant clinical value in treatment frameworks.
Improved Sensitivity in Low-Input Proteomics Using Micropillar Array-Based Chromatography

Capitalizing on the massive increase in sample concentrations which are produced by extremely low elution volumes, nano-LC-ESI-MS/MS is currently one of the most sensitive analytical technologies for the comprehensive characterization of complex protein samples. However, despite tremendous technological improvements made in the production and the packing of monodisperse spherical particles for nano-flow HPLC, current state-of-the-art systems still suffer from limits in operation at the maximum potential of the technology. With the recent introduction of the µPAC system, which provides perfectly ordered micro-pillar array based chromatographic support materials, completely new chromatographic concepts for optimization towards the needs of ultra-sensitive proteomics become available. Here we report on a series of benchmarking experiments comparing the performance of a commercially available 50 cm micro-pillar array column to a widely used nano-flow HPLC column for the proteomics analysis of 10 ng tryptic HeLa cell digest. Comparative analysis of LC-MS/MS-data corroborated that micro-pillar array cartridges provide outstanding chromatographic performance, excellent retention time stability, increase sensitivity in the analysis of low-input proteomics samples, and thus repeatedly yielded almost twice as many unique peptide and unique protein group identifications when compared to conventional nano-flow HPLC columns.
Recurrent Neural Networks for Early Detection of Heart Failure From Longitudinal Electronic Health Record Data: Implications for Temporal Modeling With Respect to Time Before Diagnosis, Data Density, Data Quantity, and Data Type.

BACKGROUND We determined the impact of data volume and diversity and training conditions on recurrent neural network methods compared with traditional machine learning methods. METHODS AND RESULTS Using longitudinal electronic health record data, we assessed the relative performance of machine learning models trained to detect a future diagnosis of heart failure in primary care patients. Model performance was assessed in relation to data parameters defined by the combination of different data domains (data diversity), the number of patient records in the training data set (data quantity), the number of encounters per patient (data density), the prediction window length, and the observation window length (ie, the time period before the prediction window that is the source of features for prediction). Data on 4370 incident heart failure cases and 30 132 group-matched controls were used. Recurrent neural network model performance was superior under a variety of conditions that included (1) when data were less diverse (eg, a single data domain like medication or vital signs) given the same training size; (2) as data quantity increased; (3) as density increased; (4) as the observation window length increased; and (5) as the prediction window length decreased. When all data domains were used, the performance of recurrent neural network models increased in relation to the quantity of data used (ie, up to 100% of the data). When data are sparse (ie, fewer features or low dimension), model performance is lower, but a much smaller training set size is required to achieve optimal performance compared with conditions where data are more diverse and includes more features. CONCLUSIONS Recurrent neural networks are effective for predicting a future diagnosis of heart failure given sufficient training set size. Model performance appears to continue to improve in direct relation to training set size.
Gymnemic Acid Ameliorate Hyperglycemia Through PI3K/AKT and AMPK Mediated Signaling Pathway in T2DM Rats.

Gymnemic acid (GA) isolated from gymnema sylvestre (Retz.) Schult has been shown to display anti-diabetic activity, however the molecular mechanisms governing these effects are unclear. In this study, GA (40, 80 mg/kg/day) was evaluated by type 2 diabetes mellitus (T2DM) rats to explore its hypoglycemic activity and underlying mechanisms of action. The results indicated that GA decreased fasting blood glucose (FBG) concentrations by 26.7 %, and lowered insulin concentrations by 16.1 % after oral administration of GA at a dose of 80 mg/kg/day for 6 weeks in T2DM rats. Our data showed that RT-PCR and Western blot analysis indicated that GA up-regulated the expression of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS), promoted the phosphorylation of protein kinase B (Akt), while down-regulated the expression of glycogen synthesis kinase-3β (GSK-3β) in T2DM rats. In addition, key proteins involved in AMPK-mediated gluconeogenesis (such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase)) were down-regulated in GA-treated T2DM rats. In summary, the hypoglycemic mechanisms of GA may be related to promoting insulin signal transduction and activating PI3K/Akt and AMPK-mediated signaling pathway in T2DM rats.
Left atrial anteroposterior diameter in dogs: reference interval, allometric scaling, and agreement with the left atrial-to-aortic root ratio

Left atrial enlargement (LAE) is a well-known negative prognostic factor in dogs with myxomatous mitral valve disease (MMVD). Left atrial-to-aortic root ratio (LA/Ao) is the most commonly used method to evaluate left atrial (LA) size in dogs, while the left atrial anteroposterior diameter (LAD) has been proposed as an additional measurement of LA size in different species. The aim of this study was to establish a normal reference range of LAD normalized to body weight (LADn) in dogs using allometric scales, and to evaluate the agreement between LADn and LA/Ao in the detection of LAE in dogs with MMVD. This was a retrospective, multicenter, observational study. We included 330 healthy dogs, 30 dogs with MMVD in ACVIM stage B1, 30 dogs in ACVIM stage B2, and 30 dogs in ACVIM stage C. The reference range for the LAD, depending on body weight, was between 16.91 mm and 49.68 mm. The reference range for the LADn in healthy dogs was between 10.49 and 15.72. LADn was significantly greater in dogs with MMVD compared to healthy dogs, and a significant difference in LADn was noted between different ACVIM stages (P<0.001). The most accurate cut-off value of LADn to differentiate between dogs in groups B2 and C was 20.3 (sensitivity, 83.3%; specificity, 83.3%). There was a misclassification rate of 37% between LADn and LA/Ao in the detection of LAE in group B1. This study provides a normal reference range for LAD in dogs, which can be used as an additional tool to assess LAE in dogs with MMVD.
Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

Significance The cryo-electron microscopy high-resolution structures of the wild-type ribosome of the human pathogen Pseudomonas aeruginosa and its uL6 rProtein mutant, isolated from a cystic fibrosis (CF) patient, shed light on the link between a distorted initiation factor 2 (IF2) binding site, a deletion in uL6, and a 50-Å distal H69–h44 B2a&b intersubunit bridges. These cumulative structural alterations interfere with the initiation of proper protein synthesis. Here, via efforts at understanding a specific and so-far-unknown aminoglycoside (AG)-resistant mechanism, we widen the concept of diversity of resistance mechanisms. Thus, we reveal a defective ribosome obtained by a conformational change of essential ribosomal intersubunit bridges and an alteration of the secondary AG binding site. Resistance to antibiotics has become a major threat to modern medicine. The ribosome plays a fundamental role in cell vitality by the translation of the genetic code into proteins; hence, it is a major target for clinically useful antibiotics. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well as of a nonresistance strain isolated from a cystic fibrosis patient. The structural studies disclosed defective ribosome complex formation due to a conformational change of rRNA helix H69, an essential intersubunit bridge, and a secondary binding site of the AGs. In addition, a stable conformation of nucleotides A1486 and A1487, pointing into helix h44, is created compared to a non-AG-bound ribosome. We suggest that altering the conformations of ribosomal protein uL6 and rRNA helix H69, which interact with initiation-factor IF2, interferes with proper protein synthesis initiation.
Clinical Reasoning: Mechanical thrombectomy for acute ischemic stroke in the setting of atrial myxoma

A 23-year-old woman with a medical history of migraines and tobacco use was brought to the emergency department with a 2-hour history of acute onset, right-sided hemiplegia and expressive aphasia. The patient had never experienced similar symptoms in the past. Her migraines occurred 3 times weekly, lasted 1–2 days, and were characterized by photophobia along with bilateral headache of a right-sided predominance. She took acetaminophen and ibuprofen for pain relief. Her family history was significant for a sister with glucose-6-phosphate dehydrogenase deficiency.
Suicidality Disparities Between Transgender and Cisgender Adolescents

Suicidality subgroup differences among TGAs remain underexplored, and our results examine subgroup differences using comprehensive measures of gender identity. BACKGROUND AND OBJECTIVES: Emerging evidence indicates transgender adolescents (TGAs) exhibit elevated rates of suicidal ideation and attempt compared with cisgender adolescents (CGAs). Less is known about risk among subgroups of TGAs because of limited measures of gender identity in previous studies. We examined disparities in suicidality across the full spectrum of suicidality between TGAs and CGAs and examined risk for suicidality within TGA subgroups. METHODS: Adolescents aged 14 to 18 completed a cross-sectional online survey (N = 2020, including 1148 TGAs). Participants reported gender assigned at birth and current gender identity (categorized as cisgender males, cisgender females, transgender males, transgender females, nonbinary adolescents assigned female at birth, nonbinary adolescents assigned male at birth, and questioning gender identity). Lifetime suicidality (passive death wish, suicidal ideation, suicide plan, suicide attempt, and attempt requiring medical care) and nonsuicidal self-injury were assessed. RESULTS: Aggregated into 1 group, TGAs had higher odds of all outcomes as compared with CGAs. Within TGA subgroups, transgender males and transgender females had higher odds of suicidal ideation and attempt than CGA groups. CONCLUSIONS: In this study, we used comprehensive measures of gender assigned at birth and current gender identity within a large nationwide survey of adolescents in the United States to examine suicidality among TGAs and CGAs. TGAs had higher odds of all suicidality outcomes, and transgender males and transgender females had high risk for suicidal ideation and attempt. Authors of future adolescent suicidality research must assess both gender assigned at birth and current gender identity to accurately identify and categorize TGAs.
Global Trends in Bumble Bee Health.

Bumble bees (Bombus) are unusually important pollinators, with approximately 260 wild species native to all biogeographic regions except Africa, Australia, and New Zealand. As they are vitally important in natural ecosystems and to agricultural food production globally, the increase in reports of declining distribution and abundance over the past decade has led to an explosion of interest in bumble bee population decline. We summarize data on the threat status of wild bumble bee species across biogeographic regions, underscoring regions lacking assessment data. Focusing on data-rich studies, we also synthesize recent research on potential causes of population declines. There is evidence that habitat loss, changing climate, pathogen transmission, invasion of nonnative species, and pesticides, operating individually and in combination, negatively impact bumble bee health, and that effects may depend on species and locality. We distinguish between correlational and causal results, underscoring the importance of expanding experimental research beyond the study of two commercially available species to identify causal factors affecting the diversity of wild species. Expected final online publication date for the Annual Review of Entomology, Volume 65 is January 7, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Identification of circulating MOG-specific B cells in patients with MOG antibodies

Objective To identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs. Methods We compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell–based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG. Results MOG-Ab–positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity. Conclusions This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell–directed therapy.