Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncertainty Aware AI ML: Why and How

This paper argues the need for research to realize uncertainty-aware artificial intelligence and machine learning (AI\&ML) systems for decision support by describing a number of motivating scenarios. Furthermore, the paper defines uncertainty-awareness and lays out the challenges along with surveying some promising research directions. A theoretical demonstration illustrates how two emerging uncertainty-aware ML and AI technologies could be integrated and be of value for a route planning operation.
Anti‐desmoglein‐1 levels as predictor of prednisolone tapering in pemphigus vulgaris patients treated with rituximab

Dear Editor, Pemphigus vulgaris (PV) is a rare, but potentially fatal autoimmune disease, which could affect both skin and mucous membranes. During this disease, autoantibodies are mainly directed against the adhesion molecules desmoglein (Dsg)1 and Dsg3, which result in acantholysis (Furue & Kadono, 2017). Although both anti-Dsg1 and anti-Dsg3 seem to be correlated with disease activity in patients with pemphigus, it was suggested that anti-Dsg1 is more representative of the disease severity (Abasq et al., 2009). During the recent decade, rituximab has been presented as an alternative treatment in pemphigus patients and also has been suggested as potential first-line therapy in moderate to severe patients (Joly et al., 2017; Tavakolpour, Mahmoudi, Balighi, Abedini, & Daneshpazhooh, 2018). In addition to relatively long-lasting remission, it can accelerate safe steroid tapering. Although some studies have suggested different (bio)markers to predict response to rituximab (Albers, Liu, Bo, Swerlick, & Feldman, 2017), two major recognized autoantibodies in pemphigus, including anti-Dsg1 and anti-Dsg3 have remained the most popular markers. Recently, it has shown that high baseline anti-Dsg1 could be associated with earlier relapse after rituximab therapy (Saleh, 2018). The association of anti-Dsg1 values and clinical response after rituximab therapy was also suggested previously (Mouquet et al., 2008). The identification of biomarkers capable of predicting responsiveness to rituximab as well as an optimum tapering schedule of steroid in rituximab-exposed patients might significantly help in better management of pemphigus patients. During a retrospective study conducted between 2015 and 2017, 90 PV patients with positive anti-Dsg1 (>20 IU/ml) or anti-Dsg3 (>20 IU/ml) being treated with rituximab (either rheumatoid arthritis protocol or lymphoma protocol) have been included (Table 1). At the baseline of rituximab treatment (T0), both anti-Dsg1 and anti-Dsg3 had been determined by using the ELISA (Euroimmun, Lübeck, Germany). According to the results of tests, patients were categorized into four groups (Table 2). The percentages of
Comparative toxicity of selected PAHs in rainbow trout hepatocytes: genotoxicity, oxidative stress and cytotoxicity

Abstract Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aquatic ecosystems, which may have potentially toxic effects on organisms. In this study occurrence of DNA strand breaks, oxidative stress, and cytotoxicity were investigated in rainbow trout hepatocytes following in vitro exposure for 24 h to four PAHs (0.01–10 µM): naphthalene, fluoranthene, pyrene, and benzo[a]pyrene (B[a]P). The exposed hepatocytes were analyzed for DNA strand breaks using the comet assay and for antioxidant status by measuring intracellular glutathione (GSH) content using the fluorescent probe mBCl. The cytotoxicity of PAHs was assessed using the fluorescent probe CFDA-AM. The results showed that fluoranthene, pyrene, and B[a]P were genotoxic at all exposure concentrations, whereas naphthalene was genotoxic at concentrations ≥0.1 µM. All treatments reduced the intracellular concentrations of GSH for all four PAHs, except 10 µM of B[a]P, suggesting that some level of oxidative stress was present. The cytotoxic effect was observed for naphthalene at concentrations ≥0.1 µM and pyrene at all exposure concentrations, whereas fluoranthene and B[a]P were not cytotoxic at the tested concentrations. The study shows that low-molecular-weight PAHs may cause DNA strand breaks as high-molecular-weight PAHs do in fish tissue. In addition, two- to five-ring PAHs can induce oxidative stress and cytotoxicity.
Stress and verbal memory in patients with Alzheimer’s disease: different role of cortisol and anxiety

Abstract Objectives: Chronic stress has shown to have marked effects on learning and memory. A broader understanding of these effects has special interest in the context of Alzheimer’s disease (AD). This study aims to analyze the moderating effect of cognitive impairment in the relationships between stress and verbal memory performance by considering biological and psychological measures of stress. Method: The sample consisted of 80 AD patients and 104 healthy controls. Salivary cortisol and state anxiety was measured as stress markers. Memory Alteration test (M@T) and Hopkins verbal learning test (HVLT-R) were used to measure verbal memory. Results: In controls, cortisol level was negatively associated with HVLT-R total, learning and delayed recall scores as well as M@T free recall scores, while in patients, such associations were not significant. In this group, cortisol negative effects were limited to HVLT-R learning and M@T semantic memory scores. In both groups, anxiety was associated with better M@T encoding and free recall scores. Besides, inverted U-shaped relationships were observed between anxiety and HVLT-R total recall and learning scores as well as M@T orientation scores. Conclusion: Cortisol levels and anxiety are differentially associated with memory performance in older adults. In general, the negative relationship between cortisol levels and memory observed in healthy elderly weakens in AD. However, moderate state anxiety levels seem to be associated with a better memory performance in AD patients and in healthy elderly.
The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies

BACKGROUND: Several authors have hypothesized that adverse drug events (ADEs) upon switching from reference biologics to biosimilar products are related to the nocebo effect. However, a thorough and current review of the existing literature has not been conducted. OBJECTIVE: To evaluate if patient and/or physician knowledge of a switch from a reference biologic product to a biosimilar product was associated with an increase in ADEs likely to be susceptible to the nocebo effect. METHODS: Studies reporting efficacy and safety outcomes of a switch from a reference product to a biosimilar product were reviewed. Biologics with FDA-approved biosimilars in the United States were considered for review, including adalimumab, bevacizumab, etanercept, and infliximab. Studies were identified by searching controlled vocabulary (e.g., MeSH terms) and keywords within MEDLINE (via PubMed) and Embase. Descriptive statistics were used to quantify subjective and objective complications in double-blinded and single-blinded or open-label studies. RESULTS: Thirty-one trials including 3,271 patients were reviewed in the full analysis. Median discontinuation rates for any reason were 14.3% (range = 0.0-33.3) in open-label studies compared with 6.95% (range = 5.2-11.0) in double-blinded studies. Discontinuation rates for ADEs were 5.6% (range = 0.0-24.2) in open-label studies versus 3.1% (range = 2.0-5.2) in double-blinded studies, suggesting the nocebo effect does affect biosimilar adoption. Subgroup analyses of antidrug antibody (ADA) development and infusion reactions were similar between infliximab open-label and double-blinded studies. Discontinuation rates for any reason, for ADEs, and for lack of efficacy were generally higher in infliximab open-label trials compared with double-blinded trials. Etanercept biosimilar discontinuation rates for any reason were similar between study designs; however, incidences of injection site reactions and discontinuation rates for ADEs were higher in double-blinded compared with open-label study designs. CONCLUSIONS: Current evidence is insufficient to confirm a biosimilar nocebo effect, although higher discontinuation rates in infliximab biosimilar open-label studies support this theory. Further studies are needed to evaluate the existence of a biosimilar nocebo effect.
C-reactive Protein Level on Postoperative Day One is Associated with Chronic Postsurgical Pain After Mastectomy

Background C-reactive protein (CRP) is an acute phase reactant released in response to inflammation or tissue injury. Inflammation is one of the pathogenic factors related to transition from acute postsurgical pain (APSP) to chronic postsurgical pain (CPSP). Although several risk factors are reportedly associated with CPSP, the effects of CRP levels on CPSP have not been examined. Objectives The present study investigated the relationship between perioperative risk factors, including CRP levels on postoperative day one and CPSP, in patients undergoing mastectomy. Methods Preoperative anxiety and depression levels were evaluated in female patients undergoing mastectomy under general anesthesia, with or without peripheral nerve block. Patients with chronic preoperative pain and/or preoperative breast pain were excluded. The intensity of postoperative pain was prospectively examined one and six days, and three and twelve months after surgery using a numerical rating scale (NRS). Results The current researchers conducted univariate and multivariate linear regression analyses to explore risk factors for CPSP in 36 patients. Patient demographics, preoperative psychological states, and anesthetic managements showed no relationship with CPSP. On the other hand, pain intensity of APSP and CRP levels on postoperative day one was significantly associated with the pain intensity of CPSP. Conclusions Postoperative CRP level is likely to be associated with the development of CPSP after mastectomy.
How Do Professionals Assess Sexual Recidivism Risk? An Updated Survey of Practices

Forensic evaluators may be assisted by comparing their use of instruments with that of their peers. This article reports the results of a 2017 survey of instrument use by forensic evaluators carrying out sexual recidivism risk assessments. Results are compared with a similar survey carried out in 2013. Analysis focuses primarily on adoption of more recently developed instruments and norms, and on assessment of criminogenic needs and protective factors, and secondarily, on exploring factors related to differences in evaluator practice. Findings indicate that most evaluators have now adopted modern actuarial instruments, with the Static-99R and Static-2002R being the most commonly used. Assessment of criminogenic needs is now common, with the STABLE-2007 being the most frequently used instrument. Evaluators are also increasingly likely to consider protective factors. While a majority of evaluators uses actuarial instruments, a substantial minority employs Structured Professional Judgment (SPJ) instruments. Few factors discriminated patterns of instrument use.
Population genomics reveals evolution and variation of Saccharomyces cerevisiae in the human and insects gut

The quest to discover the variety of ecological niches inhabited by Saccharomyces cerevisiae has led to research in areas as diverse as wineries, oak trees and insect guts. The discovery of fungal communities in the human gastrointestinal tract suggested the host's gut as a potential reservoir for yeast adaptation. Here, we report the existence of yeast populations associated with the human gut (HG) that differ from those isolated from other human body sites. Phylogenetic analysis on 12 microsatellite loci and 1715 combined CDSs from whole-genome sequencing revealed three subclusters of HG strains with further evidence of clonal colonization within the host's gut. The presence of such subclusters was supported by other genomic features, such as copy number variation, absence/introgressions of CDSs and relative polymorphism frequency. Functional analysis of CDSs specific of the different subclusters suggested possible alterations in cell wall composition and sporulation features. The phenotypic analysis combined with immunological profiling of these strains further showed that sporulation was related with strain-specific genomic characteristics in the immune recognition pattern. We conclude that both genetic and environmental factors involved in cell wall remodelling and sporulation are the main drivers of adaptation in S. cerevisiae populations in the human gut.
Over-optimization of academic publishing metrics: observing Goodhart’s Law in action

Abstract Background The academic publishing world is changing significantly, with ever-growing numbers of publications each year and shifting publishing patterns. However, the metrics used to measure academic success, such as the number of publications, citation number, and impact factor, have not changed for decades. Moreover, recent studies indicate that these metrics have become targets and follow Goodhart’s Law, according to which, “when a measure becomes a target, it ceases to be a good measure. ” Results In this study, we analyzed >120 million papers to examine how the academic publishing world has evolved over the last century, with a deeper look into the specific field of biology. Our study shows that the validity of citation-based measures is being compromised and their usefulness is lessening. In particular, the number of publications has ceased to be a good metric as a result of longer author lists, shorter papers, and surging publication numbers. Citation-based metrics, such citation number and h-index, are likewise affected by the flood of papers, self-citations, and lengthy reference lists. Measures such as a journal’s impact factor have also ceased to be good metrics due to the soaring numbers of papers that are published in top journals, particularly from the same pool of authors. Moreover, by analyzing properties of >2,600 research fields, we observed that citation-based metrics are not beneficial for comparing researchers in different fields, or even in the same department. Conclusions Academic publishing has changed considerably; now we need to reconsider how we measure success.
Canopy structure and topography jointly constrain the microclimate of human‐modified tropical landscapes

Local‐scale microclimatic conditions in forest understoreys play a key role in shaping the composition, diversity and function of these ecosystems. Consequently, understanding what drives variation in forest microclimate is critical to forecasting ecosystem responses to global change, particularly in the tropics where many species already operate close to their thermal limits and rapid land‐use transformation is profoundly altering local environments. Yet our ability to characterize forest microclimate at ecologically meaningful scales remains limited, as understorey conditions cannot be directly measured from outside the canopy. To address this challenge, we established a network of microclimate sensors across a land‐use intensity gradient spanning from old‐growth forests to oil‐palm plantations in Borneo. We then combined these observations with high‐resolution airborne laser scanning data to characterize how topography and canopy structure shape variation in microclimate both locally and across the landscape. In the processes, we generated high‐resolution microclimate surfaces spanning over 350 km2, which we used to explore the potential impacts of habitat degradation on forest regeneration under both current and future climate scenarios. We found that topography and vegetation structure were strong predictors of local microclimate, with elevation and terrain curvature primarily constraining daily mean temperatures and vapour pressure deficit (VPD), whereas canopy height had a clear dampening effect on microclimate extremes. This buffering effect was particularly pronounced on wind‐exposed slopes but tended to saturate once canopy height exceeded 20 m—suggesting that despite intensive logging, secondary forests remain largely thermally buffered. Nonetheless, at a landscape‐scale microclimate was highly heterogeneous, with maximum daily temperatures ranging between 24.2 and 37.2°C and VPD spanning two orders of magnitude. Based on this, we estimate that by the end of the century forest regeneration could be hampered in degraded secondary forests that characterize much of Borneo's lowlands if temperatures continue to rise following projected trends.
Re-experiencing 9/11-Related PTSD Symptoms Following Exposure to Hurricane Sandy.

Background Understanding Pre-Existing Posttraumatic Stress Disorder (PTSD) symptoms and risk of PTSD following Hurricane Sandy (Sandy) has important implications for PTSD screening of persons exposed to multiple traumas. This study assessed the association between Sandy exposure and a subset of PTSD symptoms related to re-experiencing trauma from the events of the September 11, 2001 (9/11). Methods We studied 4,220 respondents from a random 8,870 person sample of adult World Trade Center Health Registry enrollees who completed a post-Sandy survey between March 28 and November 7, 2013. The symptom cluster of re-experiencing 9/11 was defined using 3 out of 5 questions in the intrusion domain of the PTSD Checklist. Multivariable logistic regression, adjusting for socio-demographics, social support and any post-9/11 life threatening events prior to Sandy, was performed separately in those symptomatic and non-symptomatic of re-experiencing 9/11 prior to Sandy. Results A total of 688 enrollees (16.3%) reported re-experiencing 9/11 symptoms after Sandy (58.8% in those symptomatic prior to Sandy, and 8.7% in those non-symptomatic). A significant association between Sandy exposure and re-experiencing 9/11 was observed only among those non symptomatic prior to Sandy (adjusted odds ratio (AOR)=1.7, 95% confidence interval=1.2-2.3 for moderate Sandy exposure; AOR=2.8, 2.0-4.0 for high Sandy exposure). Conclusions Individuals with a history of trauma should be considered for early screening and counseling for mental health after a subsequent traumatic event, regardless of PTSD status, especially in 9/11 exposed populations.
Spawning behavior of Arctic charr (Salvelinus alpinus): Spawning synchrony, vibrational communication, and mate guarding

Abstract A mismatch in synchrony between male and female gamete release in external fertilizers can result in reduced or failed fertilization, sperm competition, and reduced paternity. In Arctic charr (Salvelinus alpinus), males can adopt either a guard or sneak tactic resulting in both pre‐ and postcopulatory competition between males with alternative reproduction tactics. Here, spawning behavior of free‐living Arctic charr was video‐recorded, and their reproductive behavior was analyzed. From evaluating 157 spawning events, we observed that females mainly spawned with a guarding male and that the female and the guarding male synchronized timing of gamete release under sperm competition. Although sneakers spawned with higher synchrony than the guarding male in single‐male spawning events, the average sneaker released his milt less synchronized with the female than the guarding male under sperm competition. Approximately 50% of the recorded spawning events occurred under sperm competition, where each event included an average of 2.7 males. Additionally, sneakers were more exposed to sperm competition than guarding males. An influx of males, in close proximity to the female, occurred during the behavioral sequences leading up to egg release, but this influx seemed not dependent on egg release, suggesting that something else than gonadal product attracts sneaker males to the spawning female. Just before and during the actual release of gametes, the spawning couple vibrates their bodies in close contact and it seems likely that this vibrational communication between the spawning couple, which results in a larger amplitude sound wave than seen under regular courting, reveals time of gamete release to sneaker males. Thus, vibrational communication may enable synchrony between the guarding male and the female, and this might be traded against the cost of higher detectability from surrounding sneaker males, eavesdropping in close proximity.
Relationship Between Antidepressant Therapy and Risk for Cardiovascular Events in Patients With and Without Cardiovascular Disease

Objective: The American Heart Association has endorsed depression as a cardiac risk factor and recommends screening as part of routine practice. This has been met with controversy due to inconsistencies in the data linking depression treatment to better cardiovascular outcomes. Our objective was to prospectively assess the association between depression treatment (defined as being prescribed antidepressant medication) and major adverse cardiovascular events (MACE) in patients referred for exercise stress tests. Method: Two thousand three hundred eighty-five consecutive patients presenting for myocardial perfusion exercise stress tests underwent a sociodemographic, medical, and psychiatric interview (Primary Care Evaluation of Mental Disorders [PRIME-MD]) and completed the Beck Depression Inventory (BDI). History of cardiovascular disease (CVD) and antidepressant use was self-reported and verified via chart review. Participants followed over an 8.8-year follow up, and information regarding MACE incidence (including cardiac mortality, nonfatal myocardial infarction, revascularization procedures, cerebrovascular events) was obtained from provincial administrative databases. Results: 8% (n = 190) of the sample were taking antidepressants at baseline, 41% (n = 916) had a history of CVD, and 38.7% (n = 921) had depression according to the PRIME-MD or BDI. Antidepressant treatment was associated with a 30% reduced risk of MACE (Hazard ratio [HR] = 0.697; 95% confidence interval [CI] = [0.504, 0.964]; p = .029). A 46% reduction in risk was associated with antidepressant treatment among those without CVD (HR = 0.542; 95% CI [0.299, 0.981]; p = .043). In depressed patients, a 33% reduction in risk of MACE associated with antidepressant use was seen (adjusted HR = 0.674; 95% CI [0.440, 1.033]; p = .07). Conclusions: Antidepressants may be cardio-protective among patients presenting for stress testing independent of risk factors including CVD and depression. Results support treating depression with antidepressants in this population to reduce risk of MACE.