Takshan/R1 huggingface dataset:
The Society of European Robotic Gynaecological Surgery (SERGS) Pilot Curriculum for robot assisted gynecological surgery.

PURPOSE: To set forth experiences in the context of the SERGS Pilot Curriculum-the first standardized educational program for robotic use in gynecological surgery-in terms of feasibility, effectiveness and potential for certification. METHODS: The Society of European Robotic Gynecological Surgery (SERGS) outlined a Pilot Curriculum for standardized education in robot-assisted laparoscopic gynecological surgery. Its feasibility and acceptance were checked in the form of a fellowship pilot program conducted at four European Centers of Excellence for robot-assisted surgery. Results and conclusions derived from this pilot program are presented. RESULTS: The SERGS Pilot Curriculum defines criteria for a standardized training and assessment of performance, boosts the learning curve of the candidate and increases contentment at work. Regarding face validity, it proves valuable as finally all candidates could perform the outlined procedure safely and efficiently without supervision. CONCLUSION: Due to the immense increase of robotic procedures in gynecology standardized training curricula are indispensable. This seems highly necessary to ensure patients' safety and surgical outcome. The SERGS Pilot Curriculum sets standards for a stepwise theoretical and practical training in gynecological robotic procedures. It seems feasible as instrument for accreditation as gynecologic robotic surgeon. Though as a general applicable guideline for systematic training in robot-assisted surgery, a definite curriculum should have a more definite timeline and implementation of a structured assessment of performance.
Investigation of variants in estrogen receptor genes and perinatal depression.

Objectives: Depressive symptoms are common during pregnancy and after childbirth. Estrogen levels fluctuate greatly during the course of pregnancy and may contribute to mood instability. The first aim of this case-control study was to investigate whether variants in the two estrogen receptor genes might contribute to the genetic susceptibility to pregnancy-related depression using controls that were screened for postnatal depression. The second aim was to uncover new variants in the two estrogen receptor genes. Patients and methods: Our study sample comprised 554 control subjects who had Edinburgh Postnatal Depression Scale (EPDS) scores below 7 at postnatal screening, and 159 patients with clinically diagnosed pregnancy-related depression. They were genotyped for four single-nucleotide polymorphisms (SNPs) and a dinucleotide repeat in the two genes: estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Fifty-six cases with personal and/or family history of depression of psychiatric disorders were selected for resequencing of the two genes. Results: There was no statistically significant association with perinatal depression for all five variants. However, there was a trend toward higher frequencies of the genotypes associated with higher risk of depression for rs2077647 and rs4986938 in the case group. From resequencing, two novel ESR1 variants were identified from two different patients. Conclusion: Our study that used screened controls with low EPDS scores and cases with clinically diagnosed pregnancy-related depression could not replicate the association with depression for any of the SNPs for both genotype and allele frequencies. Two novel SNPs were identified and could be further investigated in a larger sample set.
Evaluating DSM-5 Insomnia Disorder and the Treatment of Sleep Problems in a Psychiatric Population.

STUDY OBJECTIVES: With the introduction of insomnia disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), greater emphasis has been placed on the diagnosis and treatment of sleep disorder even in the presence of a coexisting mental disorder. The current study seeks to explore the clinical picture of insomnia in the context of psychiatric disorders commonly associated with sleep complaints by assessing the prevalence and correlates of DSM-5 insomnia disorder, and examining the extent to which insomnia symptoms have been addressed in this population. METHODS: Four hundred treatment-seeking outpatients suffering from depressive, bipolar affective, anxiety, and schizophrenia spectrum disorders were recruited. DSM-5 insomnia was established using the modified Brief Insomnia Questionnaire. Differences in sociodemographic factors, clinical status, impairment outcomes, and mental health services utilization were compared. Information on patients' help-seeking experiences for insomnia-related symptoms was collected to determine the treatment received and treatment effectiveness. RESULTS: Almost one-third of our sample (31.8%) had DSM-5 insomnia disorder. Those with insomnia disorder had significantly higher impairment outcomes than their counterparts but no group difference was observed for mental health services utilization. Findings based on past treatment contact for sleep problems suggest that diagnosis and treatment of insomnia is lacking in this population. CONCLUSIONS: With the new calling from DSM-5, clinicians treating psychiatric patients should view insomnia less as a symptom of their mental illnesses and treat clinical insomnia as a primary disorder. Patients should also be educated on the importance of reporting and treating their sleep complaints. Nonmedical (cognitive and behavioral) interventions for insomnia need to be further explored given their proven clinical effectiveness.
Self-competence in death work among health and social care workers: a region-wide survey in Hong Kong.

BACKGROUND: According to the Quality of Death Index, Hong Kong is lagging behind many other Western and Asian countries in the category of palliative and healthcare. To ensure the provision of high-quality palliative care, it is important to explore the self-competence of health and social care workers in coping with death work including palliative care. This region-wide study aims to assess the level of self-competence with a validated Self-Competence in Death Work Scale (SC-DWS) and examine its correlates. METHODS: The SC-DWS was administered to a cross-sectional convenience sample of health and social care workers across eight healthcare institutions between January and October 2016. Total scores for the 16-item SC-DWS and its Existential and Emotional subscales were calculated. We then examined sociodemographic variables (e.g., age, profession, place of employment) in relation to the total and subscale scores using multiple linear regression. Coding was conducted on responses to a final open-ended question asking about the personal views of the workers towards their self-competence in death work. RESULT: We collected data from 885 health and social care workers. Mean score of the SC-DWS was 60.16 (range: 16 - 80), while its Existential and Emotional subscales scored 37.90 (range: 10 - 50) and 14.46 (range: 4 - 20) respectively. Four categories of personal view towards self-competence in death work including (1) personal resources; (2) existential challenges and coping; (3) emotional challenges and coping; and (4) personal recommendations on improving self-competence were identified. In multivariate analyses, workers aged 50 or above, divorced, working in Hospice A, Rehabilitation Hospital B (where a quality improvement initiative in end-of-life care was implemented) and Acute Hospital B (a Christian institution with strong caring culture) and with personal bereavement experience had significantly higher scores, whereas nurses scored significantly lower than less-educated personal care assistants. CONCLUSION: There is still room for improvement in self-competence in death work among health and social care workers, particularly the young, nurses and those working in acute hospitals. Future initiatives should involve identifying barriers in individual healthcare institutions. Training of the provision of palliative care is necessary.
Stepping volume and intensity patterns in a multi-ethnic urban Asian population.

BACKGROUND: Accelerometer measured physical activity (PA) studies particularly in non-western populations are lacking. Therefore, this study investigated stepping activity in a multi-ethnic urban Asian population. METHODS: Adult participants from the Singapore Health Study 2 consented to accelerometer activity monitoring for 7-consecutive days. Mean daily step count, peak stepping intensity (i.e. cadence) over 1-min, 30-min and 60-min and time spent in each cadence band: 0 (non-movement), 1-19, 20-39, 40-59, 60-79, 80-99 and ≥ 100 steps/minute (moderate to vigorous PA) were calculated. RESULTS: A total of 713 participants (42% male, mean age 47.8 years) were included. Overall, the mean daily step count was 7549. Mean daily step count was significantly lower in Indians (7083 adjusted p = 0.02) but not Malays 7140 (adjusted p = 0.052) compared to Chinese (7745 steps). The proportion of Malays, Indians, and Chinese achieving < 5000 daily steps was 26%, 23% and 14%, respectively (p < 0.01). Regardless of ethnicity, approximately half of the recorded time was spent undertaking 0-steps/minute (7.9 h). CONCLUSIONS: Greater promotion of brisk walking is required in light of the low step volume and pace observed in this multi-ethnic Asian population. Ethnic differences in stepping activity were also identified which indicates a need for targeted ethnic specific health promotion interventions.
Correlation of cord blood telomere length with birth weight.

BACKGROUND: Intrauterine growth restriction affects 3% of newborns; and the lightest 10% of whom are classified as small for gestational age (SGA). These low-birth weight newborns are at increased risk of neonatal morbidity such as hypoxia and hypoglycaemia. In later life, they are at higher risk of several age-related diseases such as cardiovascular and metabolic disorders and dementia. As having short telomeres is also associated with these diseases, we tested if these newborns might already start with shorter telomeres at birth. FINDINGS: Relative telomere lengths were determined using quantitative real-time PCR in cord blood samples from 195 newborns of Chinese ancestry. Based on the telomere length normalised to a single copy gene and a reference DNA sample as internal control, we found statistically significant correlations between relative telomere length and both unadjusted and gestational age-adjusted birth weight, with the lighter newborns having shorter telomeres. The SGA birth weight group comprising the bottom 10% of the samples also had the shortest telomeres compared to the medium and heaviest birth weight groups. CONCLUSIONS: Our results indicate that there is reduction of cord blood telomere length for newborns with lower birth weight.
Novel Insights into Staphylococcus aureus Deep Bone Infections: the Involvement of Osteocytes.

Periprosthetic joint infection (PJI) is a potentially devastating complication of orthopedic joint replacement surgery. PJI with associated osteomyelitis is particularly problematic and difficult to cure. Whether viable osteocytes, the predominant cell type in mineralized bone tissue, have a role in these infections is not clear, although their involvement might contribute to the difficulty in detecting and clearing PJI. Here, using Staphylococcus aureus, the most common pathogen in PJI, we demonstrate intracellular infection of human-osteocyte-like cells in vitro and S. aureus adaptation by forming quasi-dormant small-colony variants (SCVs). Consistent patterns of host gene expression were observed between in vitro-infected osteocyte-like cultures, an ex vivo human bone infection model, and bone samples obtained from PJI patients. Finally, we confirm S. aureus infection of osteocytes in clinical cases of PJI. Our findings are consistent with osteocyte infection being a feature of human PJI and suggest that this cell type may provide a reservoir for silent or persistent infection. We suggest that elucidating the molecular/cellular mechanism(s) of osteocyte-bacterium interactions will contribute to better understanding of PJI and osteomyelitis, improved pathogen detection, and treatment. IMPORTANCE Periprosthetic joint infections (PJIs) are increasing and are recognized as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat and difficult to cure and increases patient mortality 5-fold. Staphylococcus aureus is the most common pathogen causing PJI. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Osteocytes, the major bone cell type, reside in bony caves and tunnels, the lacuno-canalicular system. We report here that S. aureus can infect and reside in human osteocytes without causing cell death both experimentally and in bone samples from patients with PJI. We demonstrate that osteocytes respond to infection by the differential regulation of a large number of genes. S. aureus adapts during intracellular infection of osteocytes by adopting the quasi-dormant small-colony variant (SCV) lifestyle, which might contribute to persistent or silent infection. Our findings shed new light on the etiology of PJI and osteomyelitis in general.
PEA: an integrated R toolkit for plant epitranscriptome analysis.

Motivation: The epitranscriptome, also known as chemical modifications of RNA (CMRs), is a newly discovered layer of gene regulation, the biological importance of which emerged through analysis of only a small fraction of CMRs detected by high-throughput sequencing technologies. Understanding of the epitranscriptome is hampered by the absence of computational tools for the systematic analysis of epitranscriptome sequencing data. In addition, no tools have yet been designed for accurate prediction of CMRs in plants, or to extend epitranscriptome analysis from a fraction of the transcriptome to its entirety. Results: Here, we introduce PEA, an integrated R toolkit to facilitate the analysis of plant epitranscriptome data. The PEA toolkit contains a comprehensive collection of functions required for read mapping, CMR calling, motif scanning and discovery and gene functional enrichment analysis. PEA also takes advantage of machine learning (ML) technologies for transcriptome-scale CMR prediction, with high prediction accuracy, using the Positive Samples Only Learning algorithm, which addresses the two-class classification problem by using only positive samples (CMRs), in the absence of negative samples (non-CMRs). Hence PEA is a versatile epitranscriptome analysis pipeline covering CMR calling, prediction and annotation and we describe its application to predict N6-methyladenosine (m6A) modifications in Arabidopsis thaliana. Experimental results demonstrate that the toolkit achieved 71.6% sensitivity and 73.7% specificity, which is superior to existing m6A predictors. PEA is potentially broadly applicable to the in-depth study of epitranscriptomics. Availability and implementation: PEA Docker image is available at https://hub.docker.com/r/malab/pea, source codes and user manual are available at https://github.com/cma2015/PEA. Supplementary information: Supplementary data are available at Bioinformatics online.
Prophylactic Cranial Irradiation in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed the literature for trials addressing the efficacy of prophylactic cranial irradiation (PCI) in patients with non-small-cell lung cancer (NSCLC) treated with a curative intent. Methods: Randomized controlled trials (RCT) comparing PCI to no PCI in patients with NSCLC treated with a curative intent were eligible for inclusion. We searched EMBASE, MEDLINE, PubMed, and CENTRAL between 1946 and July 2016. We also received continual search alerts from PubMed through September 2017. Search terms included "non-small-cell lung carcinoma," "cranial irradiation," and "randomized controlled trials." We conducted meta-analyses using random-effects models for relative measures of treatment effect for the incidence of brain metastasis, overall survival (OS), and disease-free survival (DFS). We used Parmar's methodology to derive hazard ratios (HR) when not explicitly stated in RCTs. We narratively synthesized data for the impact of PCI on quality of life (QoL) and neurocognitive function (NCF). We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. Results: Out of 3,548 citations captured by the search strategy, we retained 8 papers and 1 abstract, reporting on 6 eligible trials. Patients who received PCI had a significant reduction in the risk of developing brain metastases as compared with patients who did not [relative risk (RR) = 0.37; 95% confidence interval (CI): 0.26-0.52; moderate quality evidence]. However, there was no OS benefit (HR = 1.08, 95% CI: 0.90-1.31; moderate quality evidence). Sensitivity analysis excluding older studies did not show substantively different findings. DFS was reported in the two most recent trials that included only stage III patients. There was significant improvement in DFS with PCI (HR = 0.67; 95% CI: 0.46-0.98; high quality evidence). Two studies that reported on QoL reported no statistically significant differences. There was no significant difference in NCF decline in the only study that reported on this outcome, except in immediate and delayed recall, as assessed by the Hopkins Verbal Learning Test. Conclusion: There is moderate quality evidence that the use of PCI in patients with NSCLC decreases the risk of brain metastases, but does not provide an OS benefit. However, data limited to stage III patients suggests that PCI improves DFS, with no effect on QoL.
Blocking serotonin but not dopamine reuptake alters neural processing during perceptual decision making.

Dopamine and serotonin have opponent interactions on aspects of impulsivity. Therefore we wanted to test the hypothesis that dopamine and serotonin would have opposing effects on speed-accuracy trade offs in a perceptual decision making task. Unlike other behavioral measures of impulsivity, perceptual decision making allows us to determine whether decreasing premature responses, often interpreted as decreased impulsivity, corresponds to increased behavioral performance. We administered GBR-12909 (a dopamine transporter blocker), escitalopram (a serotonin transporter blocker), or saline in separate sessions to 3 rhesus macaques. We found that animals had slower reaction times (RTs) on escitalopram than on GBR-12909 or saline. However, they were also least accurate on escitalopram. Animals were faster, although nonsignificantly, on GBR than saline and had equivalent accuracy. Administration of GBR-12909 did cause animals to be faster in error trials than correct trials. Therefore, from the point of view of RTs the animals were less impulsive on escitalopram. However, the decreased accuracy of the monkeys shows that they were not able to make use of their slower response times to make more accurate decisions. Therefore, impulsivity was reduced on escitalopram, but at the expense of a slower information-processing rate in the perceptual inference task. ( PsycINFO Database Record
The Role of Frontal Cortical and Medial-Temporal Lobe Brain Areas in Learning a Bayesian Prior Belief on Reversals.

UNLABELLED: Reversal learning has been extensively studied across species as a task that indexes the ability to flexibly make and reverse deterministic stimulus-reward associations. Although various brain lesions have been found to affect performance on this task, the behavioral processes affected by these lesions have not yet been determined. This task includes at least two kinds of learning. First, subjects have to learn and reverse stimulus-reward associations in each block of trials. Second, subjects become more proficient at reversing choice preferences as they experience more reversals. We have developed a Bayesian approach to separately characterize these two learning processes. Reversal of choice behavior within each block is driven by a combination of evidence that a reversal has occurred, and a prior belief in reversals that evolves with experience across blocks. We applied the approach to behavior obtained from 89 macaques, comprising 12 lesion groups and a control group. We found that animals from all of the groups reversed more quickly as they experienced more reversals, and correspondingly they updated their prior beliefs about reversals at the same rate. However, the initial values of the priors that the various groups of animals brought to the task differed significantly, and it was these initial priors that led to the differences in behavior. Thus, by taking a Bayesian approach we find that variability in reversal-learning performance attributable to different neural systems is primarily driven by different prior beliefs about reversals that each group brings to the task. SIGNIFICANCE STATEMENT: The ability to use prior knowledge to adapt choice behavior is critical for flexible decision making. Reversal learning is often studied as a form of flexible decision making. However, prior studies have not identified which brain regions are important for the formation and use of prior beliefs to guide choice behavior. Here we develop a Bayesian approach that formally characterizes learning set as a concept, and we show that, in macaque monkeys, the amygdala and medial prefrontal cortex have a role in establishing an initial belief about the stability of the reward environment.
Incidentalome from Genomic Sequencing: A Barrier to Personalized Medicine?

BACKGROUND: In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated to the patient's primary condition, is between 0.86% and 8.8%. However, data on prevalence and type of IFs in Asian population is lacking. METHODS: In 2 cohorts of individuals with genomic sequencing performed in Singapore (total n = 377), we extracted and annotated variants in the 56 ACMG-recommended genes and filtered these variants based on the level of pathogenicity. We then analyzed the precise distribution of IFs, class of genes, related medical conditions, and potential clinical impact. RESULTS: We found a total of 41,607 variants in the 56 genes in our cohort of 377 individuals. After filtering for rare and coding variants, we identified 14 potential variants. After reviewing primary literature, only 4 out of the 14 variants were classified to be pathogenic, while an additional two variants were classified as likely pathogenic. Overall, the cumulative prevalence of IFs (pathogenic and likely pathogenic variants) in our cohort was 1.6%. CONCLUSION: The cumulative prevalence of IFs through genomic sequencing is low and the incidentalome may not be a significant barrier to implementation of genomics for personalized medicine.