Miracle-dz/UniFAR-FTUs huggingface dataset:
Prehabilitation is better than cure

Purpose of review With a continuously growing number of older patients undergoing major surgical procedures, reliable parameters practicable in perioperative routine revealing those patients at risk are urgently needed. Recently, the concept of ‘prehabilitation’ with its key elements exercise, nutrition and psychological stress reduction especially in frail patients is attracting increasing attention. Recent findings Literature search revealed a huge amount of publications in particular within the last 12 months. Although a single definition of both frailty and prehabilitation is still to be made, various players in the perioperative setting obviously are becoming increasingly convinced about a possible benefit of the program – referring to different components and measures performed. Although physiologically advantages seem obvious, there is hardly any reliable data on clinical outcomes resulting from properly performed studies. This applies especially to octogenarians; thus those at risk for adverse events the concept originally addresses. Summary Identifying high-risk patients at the earliest possible stage and increasing their physiological reserve prior to surgery is a promising approach that seems to result in remarkable improvements for older patients. However, further studies on effectiveness in a highly heterogeneous population and agreement on a common concept are mandatory before a final judgement can be given.
SplicePie: a novel analytical approach for the detection of alternative, non-sequential and recursive splicing

Alternative splicing is a powerful mechanism present in eukaryotic cells to obtain a wide range of transcripts and protein isoforms from a relatively small number of genes. The mechanisms regulating (alternative) splicing and the paradigm of consecutive splicing have recently been challenged, especially for genes with a large number of introns. RNA-Seq, a powerful technology using deep sequencing in order to determine transcript structure and expression levels, is usually performed on mature mRNA, therefore not allowing detailed analysis of splicing progression. Sequencing pre-mRNA at different stages of splicing potentially provides insight into mRNA maturation. Although the number of tools that analyze total and cytoplasmic RNA in order to elucidate the transcriptome composition is rapidly growing, there are no tools specifically designed for the analysis of nuclear RNA (which contains mixtures of pre- and mature mRNA). We developed dedicated algorithms to investigate the splicing process. In this paper, we present a new classification of RNA-Seq reads based on three major stages of splicing: pre-, intermediate- and post-splicing. Applying this novel classification we demonstrate the possibility to analyze the order of splicing. Furthermore, we uncover the potential to investigate the multi-step nature of splicing, assessing various types of recursive splicing events. We provide the data that gives biological insight into the order of splicing, show that non-sequential splicing of certain introns is reproducible and coinciding in multiple cell lines. We validated our observations with independent experimental technologies and showed the reliability of our method. The pipeline, named SplicePie, is freely available at: https://github.com/pulyakhina/splicing_analysis_pipeline. The example data can be found at: https://barmsijs.lumc. nl/HG/irina/example_data. tar.gz.
Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Pharmacological Treatments” is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. Results: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. Conclusions: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.
An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer

ABSTRACT After a case report of profound clinical response in a melanoma patient following treatment with an immune checkpoint inhibitor (ICI) and RANK-ligand inhibitor denosumab, we identified similar patients from electronic health records (EHR) and described patient characteristics and outcomes. This 2017 observational study used Flatiron Health’s EHR database from ~255 US cancer clinics. Included were advanced melanoma or non-small-cell lung cancer (NSCLC) patients who received denosumab within 30 days of CTLA-4 (ipilimumab) or PD1 (pembrolizumab, nivolumab) inhibitors start with a minimum of 6 months of follow up. Real-world tumor response (rwTR) was analyzed for scans available up to 30 days after concomitant therapy. Preclinical experiments evaluated sequencing of ICI, denosumab vs monotherapy or control. Melanoma (n = 66) patients received concomitant denosumab/ICI for a mean 4.0 months, 3.1 months for NSCLC (n = 241). Two-thirds of patients had best rwTR evaluable (complete [CR], partial response [PR], stable disease [SD], or disease progression [PD]). Longer mean duration of concomitant exposure was associated with overall response rate (ORR; CR+PR) in melanoma (p = 0.0172), NSCLC (p < .0001), and combined cohorts (p < .0001). The disease control rate (ORR plus SD) was 56% amongst melanoma patients and 58% amongst NSCLC patients. Longer concomitant therapy was associated with increased overall survival, primarily in NSCLC (p < .0001). Preclinical data suggest that ICI initiated before or at same time as denosumab was optimal. Results provide proof-of-concept that rwTR is associated with concomitant denosumab/ICI. Crude survival analyses supported the association of concomitant therapy and improved outcomes outside of clinical trials and warrant comparative study.
Spiteful and Contemptuous: A New Look at the Emotional Experiences Related to Psychopathy

Psychopathy has long been conceptualized in terms of an absence of emotion. Yet, recent studies have suggested that the experience of other-directed negative emotions may be more intimately linked to psychopathy than previously acknowledged, although there is limited knowledge concerning the experience of such emotions. The present study examined the disposition to experience two other-directed emotions, spitefulness and contempt, that are conceptually linked with psychopathy but currently are limited in empirical support. Across 2 studies with 3 nonclinical samples (Ns = 1,237, 239, 521), we found evidence that psychopathic traits—as assessed via the Self-Report Psychopathy Scale (SRP; Paulhus, Neumann, & Hare, 2016; Study 1 and Study 2) and the Triarchic Psychopathy Measure (TriPM; Patrick, 2010; Study 2)—were positively associated with spitefulness (Study 1) and contempt (Study 2). These associations were consistent across psychopathy instruments (SRP and TriPM) and dimensions (i.e., the SRP Interpersonal, Affective, Lifestyle, and Antisocial facets, and the TriPM Meanness and Disinhibition dimensions), were stronger for the interpersonal and affective traits of psychopathy, and held when accounting for several theoretically relevant covariates. The only exception concerned the TriPM Boldness scale, which had less consistent associations with contempt. The present findings further our understanding of the emotional experiences related to psychopathy, highlighting the relevance of focusing on other-directed negative emotions, especially those that are interpersonal in nature and share an antagonistic component.
Uniportal vs. triportal video-assisted thoracic surgery in the treatment of primary pneumothorax-a propensity matched bicentric study.

Background The role of triportal video-assisted thoracoscopic surgery (VATS) is widely recognized for the treatment of primary spontaneous pneumothorax (PSP). The aim of this study was to assess the effectiveness and the potential advantages of uniportal VATS (U-VATS) for the treatment of PSP compared with triportal VATS. Methods A total of 104 triportal (n=39) and uniportal (n=65) VATS procedures where performed for the treatment of PSP in two University hospitals. The prospectively collected data of postoperative outcomes were retrospectively reviewed and a 1:1 propensity score matching analysis was performed to compare the two VATS approaches. Results No major adverse events occurred after operation. Compared with triportal-VATS, Uniportal-VATS showed the same effectiveness in terms of risk of recurrence (null in both groups), post-operative complications (P=1.000) and operating time (66.04±16.92 vs. 74.57±21.38 min, P=0.141). However, there was a statistically significant difference in favor of uniportal-VATS in terms of necessity of further access [0 vs. 7 (30.4%), P=0.004], chest tube duration (4.39±1.41 vs. 6.32±0.94 days, P<<0.001), postoperative hospital stay (4.78±1.31 vs. 6.61±1.67 days, P<<0.001), visual analogue pain score (VAS) at 24 hours (3.45±1.41 vs. 6.44±2.45, P<<0.001), number of patients who had pain after chest drain removal [1 (4.3%) vs. 16 (69.6%), P<<0.001], VAS after drainage removal (0.11±0.47 vs. 2.74±2.25, P<<0.001), postoperative pain duration (2.50±1.20 vs. 14.82±37.41 days, P<<0.001), pain killers intake (0.75±1.06 vs. 7.53±3.96 days, P=0.001), chronic paresthesia (level scale: 0 to 2; 0 vs. 0.52±0.66, P<<0.001), chronic neuralgia (0 vs. 0.43±0.59, P<<0.001) and cosmetic results (level scale: 0 to 3; 2.91±0.28 vs. 2.00±0.77, P<<0.001). Conclusions U-VATS is feasible and safe and may be a less invasive alternative to triportal VATS for the treatment of PSP because of its effectiveness in reducing postoperative pain, paresthesia, hospital stay and in improving cosmetic results.
Interventions to promote adherence to endocrine therapy among breast cancer survivors: A meta‐analysis

Adjuvant endocrine therapy (AET) significantly reduces risk of breast cancer recurrence in those patients whose tumor tests hormone (estrogen and/or progesterone) receptor positive. Many who are prescribed AET do not adhere adequately. Studies have sought to examine the effects of interventions to enhance patients' AET adherence, with strikingly mixed results. In order to reconcile a disparate literature, this paper aims to (1) quantitatively review the aggregate effect of interventions designed to optimize AET adherence within the current literature and (2) meta‐analyze these effects across studies' by intervention design.
Impulsivity as an Endophenotype in ADHD: Negative Findings

Impulsivity has a strong genetic component and is considered an endophenotype in many psychiatric disorders. Impulsivity in adult ADHD has become a focus of interest more recently because of its suggested prominence in this age. Objective: This study aimed to access self-reported impulsivity levels in biological parents of ADHD offspring, according to their status: non-ADHD (controls), remitted, nonremitted. Method: Impulsivity levels of 155 parents of ADHD children were compared according to their status using the Barratt Impulsiveness Scale (BIS-11). Results: The ADHD group presented the highest levels of impulsivity compared with all other groups. The remitted ADHD and control groups showed no significant differences in impulsivity levels. Conclusion: Impulsivity tended to remit alongside ADHD symptoms in remitters and to persist in those presenting with the residual form of adult ADHD suggesting it should not be considered as an endophenotype. Only the attentional dimension was impaired, cautioning against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) impulsivity proposed criteria.
Examination of Differential Validity of MMPI-2-RF Scores by Gender and Ethnicity in Predicting Future Suicidal and Violent Behaviors in a Forensic Sample

Given the diversity of individuals who undergo psychological assessment, examining whether cultural bias exists in psychological assessment instruments (i.e., differential validity) is crucial. This issue occurs when a measure systematically over- or underpredicts a criterion across demographic groups or is associated with the criterion unequally across the groups. We tested the differential validity of a widely used psychological test, the Minnesota Multiphasic Personality Inventory (MMPI)-2-Restructured Form (MMPI-2-RF), as a function of gender (male, female) and ethnicity (Caucasian, African American, and Hispanic/Latino American) in large samples of forensic psychiatric inpatients. Regression models were estimated in a multigroup framework. The analyses yielded negligible to small statistical evidence of differential validity in MMPI-2-RF scores predicting the number of future suicidal behaviors and violent behaviors in the samples. This evidence supports use of the MMPI-2-RF as a generally unbiased instrument for predicting key criteria across genders and ethnicities in a forensic psychiatric population.
The influence of national culture on the practice of project management: a study of information and communication technology projects in Saudi Arabia

In an ever-shrinking world with advancing technology many organizations have expanded their operations internationally and experienced challenges of how to manage projects in areas with different cultural backgrounds. In a culturally unique country, like the Kingdom of Saudi Arabia (KSA), the influence of national culture on project management has to be considered, and there is additional complexity in that most project teams are themselves diverse and multi-cultural. KSA has become one of the wealthiest countries in the world, however, many of its projects, especially in the Information and Communication Technology (ICT) sector, still fail dramatically for financial, managerial, political, social and cultural reasons. In KSA, culture is a crucial factor in business, and the management of projects is no exception. The aim of this research is to contribute to more successful delivery of ICT projects in KSA. The overall commonly-held belief is that there are elements of national culture in KSA that impact the implementation of project management processes on ICT projects. Using Hofstede’s cultural model as a basis, a conceptual framework has been created that explores and explains the impact of KSA national culture on ICT project management as characterised by the Project Management Body of Knowledge (PMBoK)1 principles. A qualitative research approach was used to collect data from four private and public sector ICT projects, in their natural settings, using a multiple case study approach. Data were collected using semi-structured interviews and examination of project documentation and a cross-case analysis was performed. The conceptual framework is a very useful planning tool for human resourcing purposes is best used for the ICT project management professionals in understanding how project management practices, procedures, tools and techniques are implemented and how they are impacted by cultural factors. The findings in this study have confirmed that the dimensions of Power Distance Index (PDI), Individualism (IDV) and Uncertainty Avoidance (UAI) have a significant impact on project management in KSA, but that Long–Term Orientation (LTO), Masculinity (MAS) and Indulgence (IND) have a lesser impact.
Chromatin assembly factor-1 (CAF-1) chaperone regulates Cse4 deposition into chromatin in budding yeast

Abstract Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast. yCAF-1 interacts with Cse4 and can assemble Cse4 nucleosomes in vitro. Loss of yCAF-1 dramatically reduces the amount of Cse4 deposited into chromatin genome-wide when Cse4 is overexpressed. The incorporation of Cse4 genome-wide may have multifactorial effects on growth and gene expression. Loss of yCAF-1 can rescue growth defects and some changes in gene expression associated with Cse4 deposition that occur in the absence of Psh1-mediated proteolysis. Incorporation of Cse4 into promoter nucleosomes at transcriptionally active genes depends on yCAF-1. Overall our findings suggest CAF-1 can act as a CenH3 chaperone, regulating levels and incorporation of CenH3 in chromatin.
Combination of Posaconazole and Amphotericin B in the Treatment of Candida glabrata Biofilms

Candidemia cases have been increasing, especially among immunosuppressed patients. Candida glabrata is one of the most resistant Candida species, especially to the azole drugs, resulting in a high demand for therapeutic alternatives. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum biofilm eradication concentration (MBEC) were determined for posaconazole (Pcz) and amphotericin B (AmB). The drug combinations of both drugs were evaluated on pre-formed biofilms of C. glabrata ATCC 2001, through XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay, colony forming units (CFU), crystal violet, and the fractional inhibitory concentration index (FICI). C. glabrata revealed higher susceptibility and biofilm reduction in the presence of AmB alone, but both drugs revealed a good capacity in the biomass elimination. In the majority of the tested combinations, the interactions were defined as indifferent (FICI ≤ 4). The combination of the two drugs does not seem to bring a clear advantage in the treatment of biofilms of C. glabrata.
Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus)

Lassa fever (LF) survivors develop various clinical manifestations including polyserositis, myalgia, epididymitis, and hearing loss weeks to months after recovery from acute infection. We demonstrate a systemic lymphoplasmacytic and histiocytic arteritis and periarteritis in guinea pigs more than 2 months after recovery from acute Lassa virus (LASV) infection. LASV was detected in the arterial tunica media smooth muscle cells by immunohistochemistry, in situ hybridization, and transmission electron microscopy. Our results suggest that the sequelae of LASV infection may be due to virus persistence resulting in systemic vascular damage. These findings shed light on the pathogenesis of LASV sequelae in convalescent human survivors.
Identifying temporal patterns in trauma admissions: Informing resource allocation

Background Increased knowledge of the temporal patterns in the distribution of trauma admissions could be beneficial to staffing and resource allocation efforts. However, little work has been done to understand how this distribution varies based on patient acuity, trauma mechanism or need for intervention. We hypothesize that temporal patterns exist in the distribution of trauma admissions, and that deep patterns exist when traumas are analyzed by their type and severity. Study design We conducted a cross-sectional observational study of adult patient flow at a level one trauma center over three years, 7/1/2013–6/30/2016. Primary thermal injuries were excluded. Frequency analysis was performed for patients grouped by ED disposition and mechanism against timing of admission; in subgroup analysis additional exclusion criteria were imposed. Results 10,684 trauma contacts were analyzed. Trauma contacts were more frequent on Saturdays and Sundays than on weekdays (p<0.001). Peak arrival time was centered around evening shift change (6-7pm), but differed based on ED disposition: OR and ICU or Step-Down admissions (p = 0.0007), OR and floor admissions (p<0.0001), and ICU or Step-Down and floor admissions (p<0.0001). Step-Down and ICU arrival times (p = 0.42) were not different. Penetrating injuries peaked later than blunt (p<0.0001). Trauma varies throughout the year; we establish a high incidence trauma season (April to late October). Different mechanisms have varying dependence upon season; Motorcycle crashes (MCCs) have the greatest dependence. Conclusion We identify new patterns in the temporal and seasonal variation of trauma and of specific mechanisms of injury, including the novel findings that 1) penetrating trauma tends to present at later times than blunt, and 2) critically ill patients requiring an OR tend to present later than those who are less acute and require an ICU or Step-Down unit. These patients present later than those who are admitted to the floor. Penetrating trauma patients arriving later than blunt may be the underlying reason why operative patients arrive later than other patients.