Miracle-dz/UniFAR-FTUs huggingface dataset:
The interaction between CASK and the tumour suppressor Dlg1 regulates mitotic spindle orientation in mammalian epithelia

ABSTRACT Oriented cell divisions are important for the formation of normal epithelial structures. Dlg1, a tumour suppressor, is required for mitotic spindle orientation in Drosophila epithelia and chick neuroepithelia, but how Dlg1 is localised to the membrane and its importance in mammalian epithelia are unknown. We show that Dlg1 is required in non-transformed mammalian epithelial cells for oriented cell divisions and normal lumen formation. We demonstrate that the MAGUK protein CASK, a membrane-associated scaffold, is the factor responsible for Dlg1 membrane localisation during spindle orientation, thereby identifying a new cellular function for CASK. Depletion of CASK leads to misoriented divisions in 3D, and to the formation of multilumen structures in cultured kidney and breast epithelial cells. Blocking the CASK–Dlg1 interaction with an interfering peptide, or by deletion of the CASK-interaction domain of Dlg1, disrupts spindle orientation and causes multilumen formation. We show that the CASK–Dlg1 interaction is important for localisation of the canonical LGN–NuMA complex known to be required for spindle orientation. These results establish the importance of the CASK–Dlg1 interaction in oriented cell division and epithelial integrity. This article has an associated First Person interview with the first author of the paper. Highlighted Article: For mammalian epithelial cells to divide in the correct orientation and form normal luminal structures, Dlg1 must localise to the cell cortex, which is dependent on binding to CASK.
Longitudinal Changes in Physical Caregiving for Parents of Children with Cerebral Palsy

Abstract Aims: To determine changes in physical caregiving for parents of children with cerebral palsy (CP) over a two-year period based on children’s gross motor function level and age. Methods: 153 parents of children with CP rated their physical caregiving using the Ease of Caregiving for Children three times over two years. Parents and assessors classified children’s gross motor function using the Gross Motor Function Classification System (GMFCS). Physical caregiving was compared at three test times among parents of children grouped by GMFCS level (I, II–III, and IV–V) and age (1.7–5.9 and 6–11 years) using a three-way mixed ANOVA. Results: Among all analyses, a two-way interaction was found between children’s GMFCS level and test time on ease of caregiving, p < 0.01. Change over two-year period was found for parents of children in level I and II–III, p < 0.01, but not parents of children in levels IV–V. At each test time, parents of children in level I reported the greatest ease of caregiving followed by parents of children in levels II–III, and levels IV–V, who reported the lowest ease of caregiving, p < 0.001. Conclusions: Findings support evaluation and monitoring of physical caregiving for parents of children with CP over time.
Combining Inter-Subject Modeling with a Subject-Based Data Transformation to Improve Affect Recognition from EEG Signals

Existing correlations between features extracted from Electroencephalography (EEG) signals and emotional aspects have motivated the development of a diversity of EEG-based affect detection methods. Both intra-subject and inter-subject approaches have been used in this context. Intra-subject approaches generally suffer from the small sample problem, and require the collection of exhaustive data for each new user before the detection system is usable. On the contrary, inter-subject models do not account for the personality and physiological influence of how the individual is feeling and expressing emotions. In this paper, we analyze both modeling approaches, using three public repositories. The results show that the subject’s influence on the EEG signals is substantially higher than that of the emotion and hence it is necessary to account for the subject’s influence on the EEG signals. To do this, we propose a data transformation that seamlessly integrates individual traits into an inter-subject approach, improving classification results.
Medication Beliefs, HIV-Related Stigmatization, and Adherence to Antiretroviral Therapy: An Examination of Alternative Models

Abstract HIV-related stigma and beliefs about medication necessity and concerns have separately demonstrated significant associations with antiretroviral adherence in people with HIV. However, no work has examined both of these associations in the same model. Based on the necessity-concerns framework, this study examined four alternative models of relationships among HIV-related stigma, medication beliefs, and adherence. Cross-sectional analyses were used to test the four alternative models to best depict associations among HIV-related stigma, medication beliefs, and medication adherence. Models tested included two indirect effects models, an interaction model, and a simple predictors model with no interaction or indirect effects. The outcome variable was HIV medication adherence, and model fit was determined by variance accounted for, Akaike information criterion (AIC), and Bayesian information criterion (BIC) values. An interaction model between internalized stigma and medication concerns accounted for the most variance in adherence. There was also a significant indirect effect of internalized stigma on adherence via medication concerns. Medication concerns are a promising target for interventions focusing on increasing adherence among people with HIV.
Tail Fiber Protein-immobilized Magnetic Nanoparticle-based Affinity Approaches for Detection of Acinetobacter baumannii.

Acinetobacter baumannii strains are common nosocomial pathogens that can cause infections and can easily become resistant to antibiotics. Thus, analytical methods that can be used to rapidly identify A. baumannii from complex samples should be developed. Tail fiber proteins derived from the tail fibers of bacteriophages can recognize specific bacterial surface polysaccharides. For example, recombinant tail proteins, such as TF2 and TF6 derived from the tail fibers of bacteriophages ϕAB2 and ϕAB6, can recognize A. baumannii clinical isolates M3237 and 54149, respectively. Thus, TF2 and TF6 can be used as probes to target specific A. baumannii strains. Generally, TF2 and TF6 are tagged with a hexa-histidine (His6) for ease of purification. Given that His6 possesses specific affinity toward alumina through His6-Al chelation, TF2 and TF6 immobilized alumina coated magnetic nanoparticles (Fe3O4@Al2O3 MNPs) were generated through chelation under microwave-heating (power: 900 W) for 60 s in this study. The as-prepared TF2-Fe3O4@Al2O3 and TF6-Fe3O4@Al2O3 MNPs were used as affinity probes to trap trace A. baumannii M3237 and 54149, respectively, from sample solutions. Matrix-assisted laser desorption/ionization mass spectrometry capable of identifying bacteria based on the obtained fingerprint mass spectra of intact bacteria was used as the detection tool. Results demonstrated that the current approach can be used to distinguish A. baumannii M3237 from A. baumannii 54149 by using TF2-Fe3O4@Al2O3 and TF6-Fe3O4@Al2O3 MNPs as affinity probes. Furthermore, the limits of detection of the current method for A. baumannii M3237 and 54149 are ~105 cells mL-1 and ~ 104 cells mL-1, respectively. The feasibility of using the developed method to selectively detect A. baumannii M3237 and 54149 from complex serum samples was demonstrated.
The (not very) typical protonymphons of Pycnogonum litorale

Sea spiders are unique and poorly known marine chelicerates. Their larvae are even less studied, especially at the ultrastructural level. Here, we examined the hatchlings of Pycnogonum litorale (Strøm, 1,762) using histology, SEM and TEM. Existing classifications place these larvae among “typical” protonymphons, together with Nymphon brevirostre. Our results, however, revealed major differences between the two species. Hatchlings of P. litorale are endotrophic for 1–2 weeks, with yolk deposits in the body wall and a reduced secretory apparatus. They lack a body cavity, demonstrate an unusual modification of the midgut sheath cells and a complex subesophageal ganglion, which includes neuromeres of the prospective walking legs 1. These larvae also possess well‐developed glia and complex sensory structures: eyes, V‐shaped mechanoreceptive bristles, integrated chemo‐ and mechanoreceptors, and three types of concealed mechanoreceptors embedded into the body wall and only seen on the sections. In this paper we also propose a new interpretation of the pycnogonid larval types: we present a set of traits useful for diagnosis and a preliminary classification. Finally, we discuss the complexity of glial types in sea spiders and other arthropods.
Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study.

SCOPE The relationship between red wine (RW) consumption and metabolism is poorly understood. We aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS Cross-sectional analysis of 1,157 participants. Subjects were divided as non-RW consumers versus RW consumers (> 1 glass/day RW (100 mL/day)). Plasma metabolomics analysis was performed using LC-MS. Associations between 386 identified metabolites and RW consumption were assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) was performed and receiver operating characteristic curves were constructed in each of the validation datasets based on weighted models. A subset of 13 metabolites was consistently selected and discriminated RW consumers versus non-consumers. Based on the multi-metabolite model weighted with the regression coefficients of metabolites, the area under the curve was 0.83 (95% CI: 0.80-0.86). These metabolites mainly consisted of lipid species (e.g. triglycerides and phosphatidylcholines), some organic acids and alkaloids. CONCLUSIONS A multi-metabolite model identified in a Mediterranean population appeared useful to discriminate between frequent RW consumers and non-consumers. Further studies are needed to assess the contribution of these metabolites in health and disease. This article is protected by copyright. All rights reserved.
Calibration of the Relative Orientation between Multiple Depth Cameras Based on a Three-Dimensional Target

Depth cameras play a vital role in three-dimensional (3D) shape reconstruction, machine vision, augmented/virtual reality and other visual information-related fields. However, a single depth camera cannot obtain complete information about an object by itself due to the limitation of the camera’s field of view. Multiple depth cameras can solve this problem by acquiring depth information from different viewpoints. In order to do so, they need to be calibrated to be able to accurately obtain the complete 3D information. However, traditional chessboard-based planar targets are not well suited for calibrating the relative orientations between multiple depth cameras, because the coordinates of different depth cameras need to be unified into a single coordinate system, and the multiple camera systems with a specific angle have a very small overlapping field of view. In this paper, we propose a 3D target-based multiple depth camera calibration method. Each plane of the 3D target is used to calibrate an independent depth camera. All planes of the 3D target are unified into a single coordinate system, which means the feature points on the calibration plane are also in one unified coordinate system. Using this 3D target, multiple depth cameras can be calibrated simultaneously. In this paper, a method of precise calibration using lidar is proposed. This method is not only applicable to the 3D target designed for the purposes of this paper, but it can also be applied to all 3D calibration objects consisting of planar chessboards. This method can significantly reduce the calibration error compared with traditional camera calibration methods. In addition, in order to reduce the influence of the infrared transmitter of the depth camera and improve its calibration accuracy, the calibration process of the depth camera is optimized. A series of calibration experiments were carried out, and the experimental results demonstrated the reliability and effectiveness of the proposed method.
Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor Efficacy

Folate-dependent one-carbon (C1) metabolism is compartmentalized into the mitochondria and cytosol and supports cell growth through nucleotide and amino acid biosynthesis. Mitochondrial C1 metabolism, including serine hydroxymethyltransferase (SHMT) 2, provides glycine, NAD(P)H, ATP, and C1 units for cytosolic biosynthetic reactions, and is implicated in the oncogenic phenotype across a wide range of cancers. Whereas multitargeted inhibitors of cytosolic C1 metabolism, such as pemetrexed, are used clinically, there are currently no anticancer drugs that specifically target mitochondrial C1 metabolism. We used molecular modeling to design novel small-molecule pyrrolo[3,2-d]pyrimidine inhibitors targeting mitochondrial C1 metabolism at SHMT2. In vitro antitumor efficacy was established with the lead compounds (AGF291, AGF320, AGF347) toward lung, colon, and pancreatic cancer cells. Intracellular targets were identified by metabolic rescue with glycine and nucleosides, and by targeted metabolomics using a stable isotope tracer, with confirmation by in vitro assays with purified enzymes. In addition to targeting SHMT2, inhibition of the cytosolic purine biosynthetic enzymes, β-glycinamide ribonucleotide formyltransferase and/or 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase, and SHMT1 was also established. AGF347 generated significant in vivo antitumor efficacy with potential for complete responses against both early-stage and upstage MIA PaCa-2 pancreatic tumor xenografts, providing compelling proof-of-concept for therapeutic targeting of SHMT2 and cytosolic C1 enzymes by this series. Our results establish structure–activity relationships and identify exciting new drug prototypes for further development as multitargeted antitumor agents.
WITER: a powerful method for estimation of cancer-driver genes using a weighted iterative regression modelling background mutation counts

Abstract Genomic identification of driver mutations and genes in cancer cells are critical for precision medicine. Due to difficulty in modelling distribution of background mutation counts, existing statistical methods are often underpowered to discriminate cancer-driver genes from passenger genes. Here we propose a novel statistical approach, weighted iterative zero-truncated negative-binomial regression (WITER, http://grass.cgs.hku.hk/limx/witer or KGGSeq,http://grass.cgs.hku.hk/limx/kggseq/), to detect cancer-driver genes showing an excess of somatic mutations. By fitting the distribution of background mutation counts properly, this approach works well even in small or moderate samples. Compared to alternative methods, it detected more significant and cancer-consensus genes in most tested cancers. Applying this approach, we estimated 229 driver genes in 26 different types of cancers. In silico validation confirmed 78% of predicted genes as likely known drivers and many other genes as very likely new drivers for corresponding cancers. The technical advances of WITER enable the detection of driver genes in TCGA datasets as small as 30 subjects and rescue of more genes missed by alternative tools in moderate or small samples.
Mothers’ Perceptions of the Internet and Social Media as Sources of Parenting and Health Information: Qualitative Study

Background Traditionally, guidance and support to new parents have come from family, friends, and health care providers. However, the internet and social media are growing sources of guidance and support for parents. Little is known about how the internet and social media are used by parents of young infants and specifically about parental perceptions of the internet and social media as sources of parenting and infant health information. Objective The aim of this study was to explore, using qualitative methods, parental perceptions of the advantages and disadvantages of the internet and social media as sources of parenting and health information regarding their infant. Methods A total of 28 mothers participated in focus groups or individual interviews. Probing questions concerning parenting and health information sources were asked. Themes were developed in an iterative manner from coded data. Results The central themes were (1) reasons that mothers turn to the internet for parenting and health information, (2) cautionary advice about the internet, and (3) reasons that mothers turn to social media for parenting and health information. Mothers appreciated the ability to gather unlimited information and multiple opinions quickly and anonymously, but recognized the need to use reputable sources of information. Mothers also appreciated the immediacy of affirmation, support, and tailored information available through social media. Conclusions The internet and social media are rapidly becoming important and trusted sources of parenting and health information that mothers turn to when making infant care decisions.
Longitudinal phenotypes of type 1 diabetes in youth based on weight and glycemia and their association with complications.

CONTEXT Subclinical and clinical complications emerge early in type 1 diabetes and may be associated with obesity and hyperglycemia. OBJECTIVE Test how longitudinal 'weight-glycemia' phenotypes increase susceptibility to different patterns of early/subclinical complications among youth with type 1 diabetes. DESIGN SEARCH for Diabetes in Youth observational study. SETTING Population-based cohort. PARTICIPANTS Youth with type 1 diabetes (n=570) diagnosed 2002-2006 or 2008. MAIN OUTCOME MEASURES Participants were clustered based on longitudinal BMI z-score and hemoglobin A1c from a baseline visit and 5+ year follow-up visit (mean diabetes duration: 1.4±0.4 years and 8.2±1.9 years, respectively). Logistic regression modeling tested cluster associations with seven early/ subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and duration. RESULTS Four longitudinal weight-glycemia clusters were identified: The Referent Cluster (n=195, 34.3%), the Hyperglycemia Only Cluster (n=53, 9.3%), the Elevated Weight Only Cluster (n=206, 36.1%), and the Elevated Weight with Increasing Hyperglycemia "EWH" Cluster (n=115, 20.2%). Compared to the Referent Cluster, the Hyperglycemia Only Cluster had elevated odds of dyslipidemia (adjusted odds ratio (aOR) 2.22, 95% CI 1.15-4.29), retinopathy (aOR 9.98, 95% CI 2.49-40.0) and diabetic kidney disease (DKD) (aOR 4.16, 95% CI 1.37-12.62). The EWH Cluster had elevated odds of hypertension (aOR 2.18, 95% CI 1.19-4.00), dyslipidemia (aOR 2.36, 95% CI 1.41-3.95), arterial stiffness (aOR 2.46, 95% CI 1.09-5.53), retinopathy (aOR 5.11, 95% CI 1.34-19.46), and DKD (aOR 3.43, 95% CI 1.29-9.11). CONCLUSIONS Weight-glycemia phenotypes show different patterns of complications, particularly markers of subclinical macrovascular disease, even in the first decade of type 1 diabetes.
Examination of a Group Entry Model into Alcohol and other Drug (AOD) Treatment: Improvements in Attendance, Retention, and Clinical Capacity

Background Nonattendance in alcohol and other drug (AOD) treatment has been a persistent issue for service provision. The study reports on the outcomes of implementing a group intervention, titled Getting Ready for Change (GRFC), as the default entry pathway into an AOD counseling service that aimed to improve initial attendance and retention through reduced wait days and improved clinical capacity. Methods Clients of the service (N = 274) were offered either an individual appointment (baseline) between September 2015 and February 2016 or a group-based appointment (intervention) between September 2016 and February 2017. The samples were compared in terms of demographics, principal drug of concern, wait days to initial and follow-up appointments, and attendance. Results The implementation of GRFC reduced wait days to initial appointment from 15 to 5 days and improved initial attendance rates by 24%. Wait days to follow-up were reduced from 10 to 8, retention rates improved by 24%. Further, there was an increased service capacity to meet community demand. Conclusions A group entry model into AOD treatment is a novel intervention, is easy to implement, improves attendance and retention in treatment, reduces wait days, and enhances clinical capacity.
Autonomic complexity and emotion (dys-)regulation in early childhood across high- and low-risk contexts

Abstract Developing the ability to regulate one's emotions in accordance with contextual demands (i.e., emotion regulation) is a central developmental task of early childhood. These processes are supported by the engagement of the autonomic nervous system (ANS), a physiological hub of a vast network tasked with dynamically integrating real-time experiential inputs with internal motivational and goal states. To date, much of what is known about the ANS and emotion regulation has been based on measures of respiratory sinus arrhythmia, a cardiac indicator of parasympathetic activity. In the present study, we draw from dynamical systems models to introduce two nonlinear indices of cardiac complexity (fractality and sample entropy) as potential indicators of these broader ANS dynamics. Using data from a stratified sample of preschoolers living in high- (i.e., emergency homeless shelter) and low-risk contexts (N = 115), we show that, in conjunction with respiratory sinus arrhythmia, these nonlinear indices may help to clarify important differences in the behavioral manifestations of emotion regulation. In particular, our results suggest that cardiac complexity may be especially useful for discerning active, effortful emotion regulation from less effortful regulation and dysregulation.
Telemedicine-Assisted Self-Management Program for Type 2 Diabetes Patients.

Background: Lifestyle interventions with personalized self-management programs have shown benefits for patients with type 2 diabetes mellitus (T2DM), a devastating highly prevalent disease worldwide. Despite advances in drug therapy and nonpharmacological strategies achieved in the past recent years, self-management programs to be implemented in everyday life are needed. The aim of the present prospective study was to evaluate the effects, in terms of glycated hemoglobin (HbA1c) values and self-management behavior, of a telemedicine-assisted self-management program offered to T2DM patients by a large private health insurance company. Methods: Participants with T2DM included 60 adults in the intervention group (M = 59.4 years) and 55 adults in the control group (M = 58.4 years). In the beginning of the study, the intervention group was provided with a tablet computer, a glucometer, and a step counter. Additionally, they received an individual need-based telephone coaching to address and improve motivation and diabetes self-management in daily life. The control group received care as usual and were not offered additional treatment. The study examined the results of a diabetes lifestyle program after 3 months. Results: The intervention resulted in significantly greater declines in HbA1c compared with the control group. In addition, tele-assisted participants showed significant improvements in Diabetes Self-Management scale score and body mass index compared with usual care participants. Conclusions: Patients with T2DM can benefit from telemedicine-assisted self-management programs, which may offer new options for treatment and prevention of disease progression. More follow-up and research is needed to assess feasibility and effectiveness on a larger scale.