Miracle-dz/UniFAR-FTUs huggingface dataset:
Empowering Patients and Health Professionals to Address Sexual Health in the Context of Anorectal Malformations and Hirschsprung’s Disease

The aim of this study is to develop a tool that is aligned with patients’ and health professionals’ needs to address sexual health in the context of anorectal malformations and Hirschsprung’s disease. A multiphased participatory action–research was conducted. First, an inventory of needs was made through interviews (11 patients, 11 professionals), three online focus groups (4 patients, 20 professionals), and a questionnaire (38 patients). Subsequently, four cocreation sessions with in total four patients and nine professionals were organized to translate the needs into a tool (in the form of a website). The websites’ functionality was assessed via a questionnaire (n = 34). The website, directed to patients, their parents, and professionals, stimulates awareness, fills knowledge gaps, and shows possibilities for support. The website is expected to change restrictive attitudes toward sexual health and improve the legitimization of the topic needed for the allocation of resources and sexologists’ involvement in current care pathways.
[Comparison of the CONUT method with SGA and NSA for the prediction of complications, hospital stay, readmissions, and mortality].

INTRODUCTION disease-related malnutrition (DRM) is a specific type of malnutrition caused by the inflammatory response to the underlying disease. Its prevalence worldwide varies from 30 % to 50 %, being similar in Spanish hospitals. DRE is not commonly recognized but is usually misdiagnosed and generally not treated. It is associated with an increased risk of morbidity, mortality, and costs. Nutritional societies recommend that screening be performed within the first 24 to 48 hours after admission for the early detection of malnutrition. No screening tool is universally accepted. OBJECTIVES to evaluate the predictive validity (hospital stay, complications, readmissions and mortality) of the CONUT method as compared to SGA and NSA. MATERIAL AND METHOD a retrospective study included in a prospective observational study of 365 hospitalized patients from July to December 2012. RESULTS the most frequent admission services were Internal Medicine and Oncology (30.7 % and 29.3 %). Moderate and severe risk of malnutrition: CONUT, 42.2 % and 12.1 %, SGA 25.8 % and 10.1 %, and NSA 13.7 % and 14.5 %. Malnutrition evaluated using the CONUT method was significantly related to complications (p = 0.036), readmissions (p = 0.041) and mortality (p = 0.007). The ROC curves for mortality, for all the methods evaluated, showed that CONUT is the best tool. CONCLUSIONS CONUT is an automatic detection tool that can be used as a first step in the diagnosis risk of malnutrition. CONUT offers the advantage of being a prognostic factor for complications, readmission, and mortality.
Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder

Abstract Background Substance use occurs at a high rate in persons with a psychiatric disorder. Genetically informative studies have the potential to elucidate the etiology of these phenomena. Recent developments in genome-wide association studies (GWAS) allow new avenues of investigation. Method Using results of GWAS meta-analyses, we performed a factor analysis of the genetic correlation structure, a genome-wide search of shared loci, and causally informative tests for six substance use phenotypes (four smoking, one alcohol, and one cannabis use) and five psychiatric disorders (ADHD, anorexia, depression, bipolar disorder, and schizophrenia). Results Two correlated externalizing and internalizing/psychosis factor were found, although model fit was beneath conventional standards. Of 458 loci reported in previous univariate GWAS of substance use and psychiatric disorders, about 50% (230 loci) were pleiotropic with additional 111 pleiotropic loci not reported from past GWAS. Of the 341 pleiotropic loci, 152 were associated with both substance use and psychiatric disorders, implicating neurodevelopment, cell morphogenesis, biological adhesion pathways, and enrichment in 13 different brain tissues. Seventy-five and 114 pleiotropic loci were specific to either psychiatric disorders or substance use phenotypes, implicating neuronal signaling pathway and clathrin-binding functions/structures, respectively. No consistent evidence for phenotypic causation was found across different Mendelian randomization methods. Conclusions Genetic etiology of substance use and psychiatric disorders is highly pleiotropic and involves shared neurodevelopmental path, neurotransmission, and intracellular trafficking. In aggregate, the patterns are not consistent with vertical pleiotropy, more likely reflecting horizontal pleiotropy or more complex forms of phenotypic causation.
Resistance to anti-tubulin agents: From vinca alkaloids to epothilones

This review describes the mechanism of action - inhibition of microtubules - and the most important mechanisms of resistance for vinca alkaloids, taxanes and epothilones. Resistance is a major problem in vinca and taxane chemotherapy and arises in most cases from overexpression of efflux pumps that transport the drugs out of the cancer cells and from modifications of the target, the microtubules, by overexpression of tubulin isotypes or by attachment of proteins to the ends of the microtubules so that the target is no longer recognized by the drugs. In some cases, however, this process can have the opposite effect, leading to sensitization, e.g., for vinca alkaloids in cases where taxanes are not or no longer effective. The link between resistance due to efflux pumps and the pharmacokinetics and metabolism of the drugs is also covered. Other types of resistance that are addressed include detoxification of drugs within the cancer cell and blockade of apoptosis, post-translational modifications of microtubules and other protein pathways, micro-RNAs, induction of oncogenes, and cancer stem cells, which, taken together, offer particularly multifold possibilities for preventing drug activity. The use of biomarkers for the prediction of clinical outcome and for the direction of future therapy is also addressed.
The effects of acute cannabidiol on cerebral blood flow and its relationship to memory: An arterial spin labelling magnetic resonance imaging study

Background: Cannabidiol (CBD) is being investigated as a potential treatment for several medical indications, many of which are characterised by altered memory processing. However, the mechanisms underlying these effects are unclear. Aims: Our primary aim was to investigate how CBD influences cerebral blood flow (CBF) in regions involved in memory processing. Our secondary aim was to determine if the effects of CBD on CBF were associated with differences in working and episodic memory task performance. Methods: We used a randomised, crossover, double-blind design in which 15 healthy participants were administered 600 mg oral CBD or placebo on separate days. We measured regional CBF at rest using arterial spin labelling 3 h after drug ingestion. We assessed working memory with the digit span (forward, backward) and n-back (0-back, 1-back, 2-back) tasks, and we used a prose recall task (immediate and delayed) to assess episodic memory. Results: CBD increased CBF in the hippocampus (mean (95% confidence intervals) = 15.00 (5.78–24.21) mL/100 g/min, t14 = 3.489, Cohen’s d = 0.75, p = 0.004). There were no differences in memory task performance, but there was a significant correlation whereby greater CBD-induced increases in orbitofrontal CBF were associated with reduced reaction time on the 2-back working memory task ( r= −0.73, p = 0.005). Conclusions: These findings suggest that CBD increases CBF to key regions involved in memory processing, particularly the hippocampus. These results identify potential mechanisms of CBD for a range of conditions associated with altered memory processing, including Alzheimer’s disease, schizophrenia, post-traumatic stress disorder and cannabis-use disorders.
A 140 GHz area-and-power-efficient VCO using frequency doubler in 65 nm CMOS

This paper presents a compact, low-phase-noise and lowpower D-band VCO with the tuning range from 140.1 to 143.5 GHz. To improve the area and power efficiency, we avoid using signal amplification and matching circuits in the VCO, where a 70 GHz LC oscillator is directly coupled to a frequency doubler. The layout of the transistors is optimized so that the signal loss and reflection are minimized. The proposed VCO fabricated in a 65 nm CMOS technology occupies the core area of 0.05 mm2. It achieves the output power of −8 dBm and the phase noise of −108.2 dBc/Hz at 10 MHz offset with the power consumption of 24 mW from 1 V supply, which leads to the figure-of-merit (FoM) of −177.4 dBc/Hz. key words: CMOS, D-band, frequency doubler, millimeterwave silicon RFICs, voltage-controlled oscillator (VCO). Classification: Microwave and millimeter wave devices, circuits, and hardware
Immunoradiotherapy as an Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent

Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy.
Psychosocial and Clinical Risk Factors Associated with Substance Use in Observational Cohort of Patients with Sickle Cell Disease

Abstract Background Patients with sickle cell disease (SCD) experience high rates of chronic pain, and have a high burden of mental health comorbidities shown to negatively influence health. There is limited research on substance use among individuals with SCD. Objective: The aim of this study is to measure the prevalence of substance use in patients with SCD and determine whether psychosocial or clinical risk factors are associated with substance use. Methods: This study was conducted as part of an observational study of patients with SCD at two academic medical centers. We asked participants (ages 15 and older) about the lifetime use of heroin, cocaine, amphetamines, and marijuana/cannabis. We measured stigma, depression, urban life stress, pain catastrophizing, and asked about a brief pain inventory. Results: Of 258 participants, 24.9% (n = 71) reported substance use. Marijuana was the most common substance used (22.5%; n = 65). The mean depressive score met criteria for positive screen amongst individuals who reported a history of substance use (mean 10.7(5.76)). Adjusting for age, sex, yearly family income, and education level, odds of substance use increased with higher levels of internalized stigma (aOR: 1.38; 95% CI: 1.07, 1.77; p = 0.012); higher urban life stress scores (aOR 1.06; 95% CI: 1.01, 1.12; p = 0.017) and higher pain catastrophizing scores (aOR: 1.03; 95% CI: 1.01, 1.06; p = 0.008). Conclusions: Among individuals with SCD who endorse substance use, there was markedly more stress and distress with higher rates of depression and poorer quality of life. Interventions focusing on improving distress tolerance and coping to not only pain, but also social stressors, might reduce substance use.
Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis

The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual’s risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25–22.0), IgG burden (3.79, 1.78–8.08), LPS (2.19, 1.38–3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10–18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.
Letter to the Editor: Interferon Is Not an Optimal Treatment for Chronic Hepatitis Delta but Needs “Fair Treatment” by Us

Kamal et al. assessed the impact of hepatitis D virus (HDV) viremia on liver related outcomes (1). The study reveals the real world situation of the management of chronic hepatitis D (CHD) in a country where the disease is rare. Active viral replication was associated with liver related events in CHD. In their study, 108 patients received interferon (IFN) therapy, and 19 became HDV RNA negative at 24/48 week after IFN treatment. Viral response was not associated with lower risk of liver related events.
Mechanism of aortic injury in nearside left lateral automotive crashes: A finite element accident injury reconstruction approach

Traumatic rupture of the aorta (TRA) remains the second most common cause of death associated with motor vehicle crashes (MVC), only less prevalent than brain injury. On an average, nearly 8,000 people die annually in the United States due to blunt injury to the aorta. It is observed that over 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest cavity. There have been numerous hypotheses for aortic injury in the literature but it is imperative to draw a distinction between the injury mechanisms in different directions of impact. Eight real world crashes were reconstructed in two stages using a combination of accident investigation data from the Crash Injury Research and Engineering Network (CIREN) database, finite element (FE) vehicle models, and Wayne State Human Body Model (WSHBM). Further, 16 design of computer experiments (DOCE) simulations were carried out to understand the effect of key factors (Principle Direction of Force (PDOF), impact position, impact angle, velocity of impact, and the bumper profile of striking vehicle) on average maximum principal strain (AMPS) and maximum pressure in the aorta. In order to get a better understanding of the mechanism of TRA, a sensitivity study was performed using a combination of WSHBM and a variation of PDOF. The AMPS and maximum pressure due to longitudinal stretch of the thoracic aorta was the highest at a PDOF of 270 degrees of impact and the occupant seated adjacent to the B-pillar. As the PDOF increased from 250 degrees to 310 degrees, the aortic arch transitioned from a caudomedial motion of the thoracic spine relative to the sternum (owing to thoracic deformation from the intruding B-pillar) to posterior-anterior motion of the thoracic aorta relative to the ascending aorta due to thoracic compression (greater than 300-degree impact).
Major bleeding risk and mortality associated with antiplatelet drugs in real-world clinical practice. A prospective cohort study

Background Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. Methods and findings A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013–2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. Conclusion The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. Trial registration NCT02886533.
An evaluation of gabapentin and pregabalin usage in the treatment of neuropathic pain related to spinal cord injury

Aim: In the present study, we aimed to systematically evaluate the effects of gabapentin and pregabalin, which are believed to be safe and well-tolerated and have analgesic, anticonvulsant, and anxiolytic effects, in the treatment of neuropathic pain after spinal cord injury despite their high side effect profiles.Material and Methods: A literature search of numerous electronic databases was performed. A combination of key words was used to retrieve studies published until November 1, 2018 correlated with the point of interest. The key words used were as follows: Â“spinal cord injury,Â” Â“neuropathic pain,Â” Â“gabapentin,Â” and Â“pregabalin. Â” Studies that met the inclusion criteria and were Level of I clinical trials were included in the study. The included studies were statistically evaluated. Results: In total, 125,515 publications were retrieved using the aforementioned key words. 19 studies on the use of gabapentin and pregabalin for the treatment of neuropathic pain associated with spinal cord injury were retrieved through. Conclusion: Studies suggested that available treatment modalities did not provide satisfactory outcomes for patients with neuropathic pain related to spinal cord injury. However, gabapentin and pregabalin were preferred as the first-line drugs in the treatment of neuropathic pain. The efficacy of gabapentin in the treatment of neuropathic pain after spinal cord injury has only been investigated in a few recent studies; data in these studies are not sufficiently clear and will need further clarification.
Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

Nitrogen mustard (NM) and sulfur mustard are cytotoxic alkylating agents that cause severe and progressive damage to the respiratory tract. Evidence indicates that macrophages play a key role in the acute inflammatory phase and the later resolution/profibrotic phase of the pathogenic response. These diverse roles are mediated by inflammatory macrophages broadly classified as M1 proinflammatory and M2 anti‐inflammatory that sequentially accumulate in the lung in response to injury. The goal of the present study was to identify signaling mechanisms contributing to macrophage activation in response to mustards. To accomplish this, we used RNA sequencing to analyze the gene expression profiles of lung macrophages isolated 1 and 28 days after intratracheal exposure of rats to NM (0.125 mg/kg) or phosphate‐buffered saline control. We identified 641 and 792 differentially expressed genes 1 and 28 days post‐NM exposure, respectively. These genes are primarily involved in processes related to cell movement and are regulated by cytokines, including tumor necrosis factor‐α, interferon‐γ, and interleukin‐1β. Some of the most significantly enriched canonical pathways included STAT3 and NF‐κB signaling. These cytokines and pathways may represent potential targets for therapeutic intervention to mitigate mustard‐induced lung toxicity.
The Logic of Evaluation Independence and Its Relevance to International Financial Institutions

This chapter is about the role of independent evaluation in organizations, in particular in international organizations. Evaluation must be free from external pressure if it is to produce meaningful evidence in support of institutional learning and effective and accountable decision making. Thus, a critical aspect of independent evaluation is that evaluators do not report to those in charge of the programs or practices that are being evaluated. But how does independent evaluation strengthen organizational effectiveness and facilitate organizational reform? Why is it needed to generate objective scrutiny of policies, programs, and processes? Why is attesting to the validity of self-evaluation processes important to achieve accountability and learning in public organizations? These questions are especially relevant for international financial institutions (IFIs). 1 To learn from experience and keep up with the rapid changes taking place in their operating environment, IFIs need objective evidence regarding the effectiveness of their operations. Further, they need to nurture public trust in the integrity of their decision making. An independent evaluation function can contribute to these goals by providing a credible assessment of their performance. The chapter is organized as follows. The first section makes the case for evaluation independence and outlines its essential features. The second section shows that independent evaluation is a powerful instrument of organizational learning. The third section identifies the complementary roles of independent and selfevaluation. The fourth section addresses the size of the evaluation function. The