Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of rest–activity and light exposure rhythms with sleep quality in insomnia patients

ABSTRACT The relevance of altered rest-activity rhythm (RAR) and light exposure rhythm (LER) in insomnia patients under natural conditions remains unclear. The aim of this study was to compare the parametric and nonparametric circadian variables of RAR and those of LER under natural conditions between insomnia patients and normal controls (NC) in a community-dwelling setting. The relationship of the nonparametric variables with sleep quality was also explored in both groups. Participants above 18 years old were recruited from three Public Health Centers in a rural area of Korea. Actigraphy (Actiwatch 2; Philips Respironics, Murrysville PA, USA) recording was conducted for 7 days. Subjects were eligible for our study if they had an insomnia disorder (ID) for at least 1 month. Actigraphy data of 78 normal control (NC) subjects (Age, 55.95 ± 13.22 years) and 104 patients with insomnia disorder (ID) (Age, 62.14 ± 12.34 years) were included for the analysis. Acrophases and amplitudes of RAR and LER were estimated using cosinor analysis. Interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA) of these rhythms were determined using nonparametric methods. Parametric cosinor and nonparametric variables of RAR and LER were compared between the NC and ID groups. Generalized linear models (GLMs) were applied to evaluate the main effects of group and each nonparametric variable as well as a group by each variable interaction on the sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO) reflecting sleep quality. Among sleep parameters, the ID group showed significantly lower SE and greater WASO than the NC group. There were no significant differences in the acrophase and amplitude of RAR and LER between the two groups. There were no significant differences in IV, IS, and RA of RAR and LER between the two groups either. GLMs for RAR revealed a significant interaction between the group and IS on the SOL (β = −46.39, p < 0.01), indicating a negative relationship of the IS with SOL in ID unlike its positive relationship in NC. There were no significant main effects of IV on the SOL, SE, and WASO, but significant main effects of RA on the SE and WASO (β = 63.65 and β = −221.43, respectively, p < 0.01). GLMs for LER revealed no significant main effects of IS, IV or RA on the SOL, SE, and WASO, but significant interactions between group and RA on the SE and WASO (β = 56.17 and β = −171.93, respectively, p < 0.05), indicating a stronger positive relationship of the RA with SE in ID compared to NC, and a negative relationship of the RA with WASO in ID, unlike its positive relationship in NC. Although our study did not reveal group differences in circadian variables of RAR and LER, it suggested that the regularity of RAR could be positively associated with sleep initiation, while the robustness of LER could be positively associated with sleep maintenance in insomnia patients.
Dissecting erm(41)-Mediated Macrolide-Inducible Resistance in Mycobacterium abscessus

Macrolides are the cornerstone of Mycobacterium abscessus multidrug therapy, despite that most patients respond poorly to this class of antibiotics due to the inducible resistance phenotype that occurs during drug treatment. This mechanism is driven by the macrolide-inducible ribosomal methylase encoded by erm(41), whose expression is activated by the transcriptional regulator WhiB7. ABSTRACT Macrolides are the cornerstone of Mycobacterium abscessus multidrug therapy, despite that most patients respond poorly to this class of antibiotics due to the inducible resistance phenotype that occurs during drug treatment. This mechanism is driven by the macrolide-inducible ribosomal methylase encoded by erm(41), whose expression is activated by the transcriptional regulator WhiB7. However, it has been debated whether clarithromycin and azithromycin differ in the extent to which they induce erm(41)-mediated macrolide resistance. Herein, we show that macrolide resistance is induced more rapidly in various M. abscessus isolates upon exposure to azithromycin than to clarithromycin, based on MIC determination. Macrolide-induced expression of erm(41) was assessed in vivo using a strain carrying tdTomato placed under the control of the erm(41) promoter. Visualization of fluorescent bacilli in infected zebrafish demonstrates that azithromycin and clarithromycin activate erm(41) expression in vivo. That azithromycin induces a more rapid expression of erm(41) was confirmed by measuring the β-galactosidase activity of a reporter strain in which lacZ was placed under the control of the erm(41) promoter. Shortening the promoter region in the lacZ reporter plasmid identified DNA elements involved in the regulation of erm(41) expression, particularly an AT-rich motif sharing partial conservation with the WhiB7-binding site. Mutation of this motif abrogated the macrolide-induced and WhiB7-dependent expression of erm(41). This study provides new mechanistic information on the adaptive response to macrolide treatment in M. abscessus.
CBNA: A control theory based method for identifying coding and non-coding cancer drivers

A key task in cancer genomics research is to identify cancer driver genes. As these genes initialise and progress cancer, understanding them is critical in designing effective cancer interventions. Although there are several methods developed to discover cancer drivers, most of them only identify coding drivers. However, non-coding RNAs can regulate driver mutations to develop cancer. Hence, novel methods are required to reveal both coding and non-coding cancer drivers. In this paper, we develop a novel framework named Controllability based Biological Network Analysis (CBNA) to uncover coding and non-coding cancer drivers (i.e. miRNA cancer drivers). CBNA integrates different genomic data types, including gene expression, gene network, mutation data, and contains a two-stage process: (1) Building a network for a condition (e.g. cancer condition) and (2) Identifying drivers. The application of CBNA to the BRCA dataset demonstrates that it is more effective than the existing methods in detecting coding cancer drivers. In addition, CBNA also predicts 17 miRNA drivers for breast cancer. Some of these predicted miRNA drivers have been validated by literature and the rest can be good candidates for wet-lab validation. We further use CBNA to detect subtype-specific cancer drivers and several predicted drivers have been confirmed to be related to breast cancer subtypes. Another application of CBNA is to discover epithelial-mesenchymal transition (EMT) drivers. Of the predicted EMT drivers, 7 coding and 6 miRNA drivers are in the known EMT gene lists.
Finding the best fit: examining the decision-making of augmentative and alternative communication professionals in the UK using a discrete choice experiment

Objectives Many children with varied disabilities, for example, cerebral palsy, autism, can benefit from augmentative and alternative communication (AAC) systems. However, little is known about professionals’ decision-making when recommending symbol based AAC systems for children. This study examines AAC professionals’ preferences for attributes of AAC systems and how they interact with child characteristics. Design AAC professionals answered a discrete choice experiment survey with AAC system and child-related attributes, where participants chose an AAC system for a child vignette. Setting The survey was administered online in the UK. Participants 155 UK-based AAC professionals were recruited between 20 October 2017 and 4 March 2018. Outcomes The study outcomes were the preferences of AAC professionals’ as quantified using a mixed logit model, with model selection performed using a step-wise procedure and the Bayesian Information Criterion. Results Significant differences were observed in preferences for AAC system attributes, and large interactions were seen between child attributes included in the child vignettes, for example, participants made more ambitious choices for children who were motivated to communicate using AAC, and predicted to progress in skills and abilities. These characteristics were perceived as relatively more important than language ability and previous AAC experience. Conclusions AAC professionals make trade-offs between attributes of AAC systems, and these trade-offs change depending on the characteristics of the child for whom the system is being provided.
Stearoyl-CoA desaturase (scd1a) is epigenetically regulated by broodstock nutrition in gilthead sea bream (Sparus aurata)

ABSTRACT The aim of this study was to generate new knowledge on fish epigenetics, assessing the effects of linolenic acid (ALA) conditioning of broodstock in the offspring of the marine fish Sparus aurata. Attention was focused on gene organization, methylation signatures and gene expression patterns of fatty acid desaturase 2 (fads2) and stearoyl-CoA desaturase 1a (scd1a). Blat searches in the genomic IATS-CSIC database (www.nutrigroup-iats.org/seabreamdb) highlighted a conserved exon-intron organization, a conserved PUFA response region, and CG islands at the promoter regions of each gene. The analysed CpG positions in the fads2 promoter were mostly hypomethylated and refractory to broodstock nutrition. The same response was achieved after conditioning of juvenile fish to low water oxygen concentrations, thus methylation susceptibility at individual CpG sites seems to be stringently regulated in fish of different origin and growth trajectories. Conversely, the scd1a promoter was responsive to broodstock nutrition and the offspring of parents fed the ALA-rich diet shared an increased DNA-methylation, mainly in CpG sites neighbouring SP1 and HNF4α binding sites. Cytosine methylation at these sites correlated inversely with the hepatic scd1a expression of the offspring. Co-expression analyses supported that the HNF4α-dependent regulation of scd1a is affected by DNA methylation. The phenotypic output is a regulated liver fat deposition through changes in scd1 expression, which would also allow the preservation of fatty acid unsaturation levels in fish fed reduced levels of n-3 LC-PUFA. Collectively, these findings reveal a reliable mechanism by which parent’s nutrition can shape scd1a gene expression in the fish offspring.
Deep Reinforcement Learning applied to the game Bubble Shooter

In 2013 Google Deepmind invented a new algorithm, deep reinforcement learning, which led to revolutionary results. The algorithm was able to play on 46 diﬀerent Atari games and beat a human expert in some of the games. In this research deep reinforcement learning will be applied to the game Bubble Shooter in order to create the self-learning agent AlphaBubble. A diﬀerent game state representation is used than in the original algorithm, also experiments have been conducted with bigger action spaces. The performance of AlphaBubble has clearly become better than a random Bubble Shooter agent, although it has not been able to exceed human play yet. However, AlphaBubble should be able to invent superhuman behaviour in the future.
Pubertal timing and adult fracture risk in men: A population-based cohort study

Background Puberty is a critical period for bone mass accrual, and late puberty in boys is associated with reduced bone mass in adult men. The role of variations in pubertal timing within the normal range for adult fracture risk in men is, however, unknown. We, therefore, assessed the association between age at peak height velocity (PHV), an objective measure of pubertal timing, and fracture risk in adult men. Methods and findings In the BMI Epidemiology Study Gothenburg, 31,971 Swedish men born between January 1, 1945, and December 31, 1961, with detailed growth data (height and weight) available from centrally archived school healthcare records and the conscription register were followed until December 31, 2016. Age at PHV was calculated according to a modified infancy–childhood–puberty model, and fracture information was retrieved from the Swedish National Patient Register. The mean ± SD age at PHV was 14.1 ± 1.1 years. In total, 5,872 men (18.4%) sustained at least 1 fracture after 20 years of age and 5,731 men (17.9%) sustained a non-vertebral fracture after 20 years of age during a mean ± SD follow-up of 37.3 ± 11.7 years. Cox proportional hazards models adjusted for birth year and country of origin revealed that age at PHV was associated with the risk of any fracture and non-vertebral fracture. Participants with age at PHV in the highest tertile (after 14.5 years of age) were at greater risk of any fracture (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08–1.22, P < 0.001) and non-vertebral fracture (HR 1.16, 95% CI 1.09–1.24, P < 0.001) compared with those with age at PHV in the lowest tertile (at 13.6 years of age or younger). Additional adjustments for birthweight, childhood BMI, adult educational level, and young adult height did not attenuate the associations between age at PHV and adult fracture risk. Limitations of this study include the inability to adjust for important risk factors for fracture, inadequate power to assess the relation between pubertal timing and specific fracture types, and the limited generalizability to other populations. Conclusions In this study, we observed that late pubertal timing was associated with increased adult fracture risk in men. These findings suggest that information on pubertal timing might aid in the identification of those men at greatest risk of fracture.
GeneXpert Mycobacterium tuberculosis/rifampicin assay for molecular epidemiology of rifampicin-Resistant Mycobacterium tuberculosis in an Urban Setting of Banten province, Indonesia

Background: Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2017, the World Health Organization (WHO) estimated that only 2% of the TB patients in Indonesia had only been tested with rapid diagnostics at the time of diagnosis, resulting in largely underdetected rifampicin-resistant TB (RR-TB). Utilization of GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay as a point-of-care molecular assay to detect TB and RR-TB and serving its purpose in accordance with the first pillar of the WHO End-TB Strategy. Objective: This study investigated the use of GeneXpert MTB/RIF assay to determine the molecular epidemiology of RR-TB in an urban setting of Indonesia. Methods: All molecular epidemiological and microbiological databases were retrospectively examined from GeneXpert MTB/RIF assay results in Siloam Hospital Lippo Village. The sociodemographic characteristics and results of microbiological examinations consisting of Ziehl–Neelsen staining and GeneXpert MTB/RIF assay were analyzed. Results: During the study period, 600 cases were registered, and GeneXpert MTB/RIF tests were done in which the tests yielded 597 (99.5%) valid results; 62.0% were male and adult of age category; of whom 29 samples (4.9%) were found to be RR-TB, 186 samples (31.2%) were RIF sensitive, and remainders were negative. Conclusions: The results of GeneXpert MTB/RIF to be a fundamental diagnosis of RR-TB and subsequently to notify MDR-TB were satisfying and valuable in this study. This further increased and reinforced TB surveillance and national TB program to finally bring about WHO end-TB strategy one step closer in Indonesia.
Fine-Tuning Semiconducting Polymer Self-Aggregation and Crystallinity Enables Optimal Morphology and High-Performance Printed All-Polymer Solar Cells.

Polymer aggregation and crystallization behavior play a crucial role in the performance of all-polymer solar cells (all-PSCs). Gaining control over polymer self-assembly via molecular design to influence bulk-heterojunction active-layer morphology, however, remains challenging. Herein, we show a simple yet effective way to modulate the self-aggregation of the commonly used naphthalene diimide (NDI)-based acceptor polymer (N2200), by systematically replacing a certain amount of alkyl side-chains with compact bulky side-chains (CBS). Specifically, we have synthesized a series of random co-polymer (PNDI-CBSx) with different molar fractions (x = 0-1) of the CBS units and have found that both solution-phase aggregation and solid-state crystallinity of these acceptor polymers are progressively suppressed with increasing x as evidenced by UV-Vis absorption, photoluminescence (PL) spectroscopies, thermal analysis and grazing incidence X-ray scattering (GIWAXS) techniques. Importantly, compared to the highly self-aggregating N2200, photovoltaic results show that blending of more amorphous acceptor polymers with donor polymer (PBDB-T) can enable all-PSCs with significantly increased PCE (up to 8.5%). The higher short-circuit current density (Jsc) results from the smaller polymer phase-separation domain sizes as evidenced by PL quenching and resonant soft X-ray scattering (R-SoXS) analyses. Additionally, we show that the lower crystallinity of the active layer is less sensitive to the film deposition methods. Thus, the transition from spin-coating to solution coating can be easily achieved with no performance losses. On the other hand, decreasing aggregation and crystallinity of the acceptor polymer too much, reduces the photovoltaic performance as the donor phase-separation domain sizes increases. The highly amorphous acceptor polymers appear to induce formation of larger donor polymer crystallites. These results highlight the importance of a balanced aggregation strength between the donor and acceptor polymers to achieve high-performance all-PSCs with optimal active layer film-morphology.
Comparison of automated crystallographic model-building pipelines.

A comparison of four protein model-building pipelines (ARP/wARP, Buccaneer, PHENIX AutoBuild and SHELXE) was performed using data sets from 202 experimentally phased cases, both with the data as observed and truncated to simulate lower resolutions. All pipelines were run using default parameters. Additionally, an ARP/wARP run was completed using models from Buccaneer. All pipelines achieved nearly complete protein structures and low Rwork/Rfree at resolutions between 1.2 and 1.9 Å, with PHENIX AutoBuild and ARP/wARP producing slightly lower R factors. At lower resolutions, Buccaneer leads to significantly more complete models.
Exploring Anxiety at Home, School, and in the Community Through Self‐Report From Children on the Autism Spectrum

Research investigating anxiety in children on the autism spectrum usually reports caregiver rather than self‐report perspectives. This study aimed to document children's own descriptions of their anxiety symptomatology by combining profiles on a standardized autism‐specific self‐report measure of anxiety (ASC‐ASD‐C) with the answers from closed‐ and open‐answer questions about anxiety across home, school, and community settings. Across the sample of 113 children on the spectrum aged 6–14 years, the two most frequently endorsed items on the ASC‐ASD‐C were from the Uncertainty and Performance Anxiety subscales, and the least endorsed were both from the Anxious Arousal subscale. Almost all (96.5%) of the children on the spectrum reported experiencing anxiety in at least one setting, with 40.7% reporting anxiety in all three contexts (home, school, and community). Approximately half of the sample felt their anxiety goes unrecognized by others at school and almost 60% felt it was unrecognized by others when out in the community. The proportion of children reporting having someone to help reduce their anxiety differed across home (86%), school (76%), and community (45%) settings. This highlights the importance of understanding anxiety and its impact, not only within the context of autism but also for each particular child. Autism Res 2020, 13: 603–614. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Oral Leukoerythroplakia- A Case Report

Objective: The objective of this study was to report a case of oral leukoerythroplakia, which is a potentially malignant disorder and has a high malignant transformation rate. Method: A 58 year old male patient reported with the chief complaint of burning sensation on his right inner cheek region. On clinical examination he was diagnosed as a case of oral leukoerythroplakia and excisional biopsy was performed. Results: Excisional biopsy revealed a highly dysplastic atrophic parakeratinized epithelium with dense inflammatory infiltrate, confirming the clinical diagnosis of oral leukoerythroplakia. Conclusion: All mixed red lesions should be examined carefully since many of these could turn out to be oral leukoerythroplakia.
END RESULTS OF FRACTURES OF THE PROXIMAL HUMERAL EPIPHYSIS

All of the eleven cases of fracture of the proximal humeral epiphysis presented in this series were torsion fractures occurring between the cartilage plate and the shaft proper (Type-1 fracture) No compression fractures of the epiphysis were seen. This type of epiphyseal injury, which is common in the ankle, the writer believes to be rare in this epiphysis, due to the mobility of the humeral head. In no case is there deformity, although accurate reduction was not obtained in six of the cases. Malposition is, therefore, not a cause of deformity. Premature ossification does occur, as does retardation of growth. Shortening was not only much more common in this epiphysis than in the distal radial and tibial epiphyses, but was also more marked. The fact that this shortening could not be detected clinically in any case is due to the fact that the arm is non-weight-bearing and consists of but one bone. In general, the end results obtained in all of the cases in this series were good.
The quality of life in type I diabetic patients with end‐stage kidney disease before and after simultaneous pancreas‐kidney transplantation: a single‐center prospective study

Simultaneous pancreas‐kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end‐stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life—Short‐Form Health Survey (KDQOL‐SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1–3, and >3 years). Mean KDQOL‐SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients’ stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.