Miracle-dz/UniFAR-FTUs huggingface dataset:
Why the Failure? How Adversarial Examples Can Provide Insights for Interpretable Machine Learning

Recent advances in Machine Learning (ML) have profoundly changed many detection, classification, recognition and inference tasks. Given the complexity of the battlespace, ML has the potential to revolutionise how Coalition Situation Understanding is synthesised and revised. However, many issues must be overcome before its widespread adoption. In this paper we consider two - interpretability and adversarial attacks. Interpretability is needed because military decision-makers must be able to justify their decisions. Adversarial attacks arise because many ML algorithms are very sensitive to certain kinds of input perturbations. In this paper, we argue that these two issues are conceptually linked, and insights in one can provide insights in the other. We illustrate these ideas with relevant examples from the literature and our own experiments.
Advances in the use of reflectance confocal microscopy in melanoma

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of melanoma. RCM generates a horizontal view of the skin, whereby cellular and subcellular (e.g., nuclei, melanophages, collagen) structures, to the level of the upper dermis, are projected onto a screen at near-histological resolution. Morphologic descriptors, standardized terminology, and diagnostic algorithms are well established for the RCM assessment of melanoma, melanocytic, and nonmelanocytic lesions. Clinical applications of RCM in melanoma are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. This review will provide an overview of RCM technology, findings by melanoma subtype, clinical applications, as well as explore the accuracy of RCM for melanoma diagnosis, pitfalls and emerging uses of this technology ex vivo.
Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway inflammation

Epithelial cells (ECs)‐derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type‐2‐cell‐mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata. We found that toll‐like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C‐C chemokine ligand‐2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin (TSLP) production through the NF‐κB and JNK signaling pathways to extend the survival of recruited basophils and resident DCs in the lung, predisposing a type‐2‐cell‐mediated airway inflammation. Conversely, TLR2 deficiency impaired secretion of TSLP and CCL2, decreased infiltration of lung basophils, and increased resistance to Th2 response. Blocking TSLP also phenocopied these phenomena. Our findings reveal a pro‐inflammatory role of airway ECs through a TLR2‐dependent TSLP production, which may have implication for treating allergic asthma.
Structural Variants and Selective Sweep Foci Contribute to Insecticide Resistance in the Drosophila Genetic Reference Panel

Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.
Bone marrow–derived mesenchymal stem cells–derived exosomes prevent oligodendrocyte apoptosis through exosomal miR‐134 by targeting caspase‐8

Ischemic stroke causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. The microRNA‐134 (miR‐134) is involved in regulating the process of ischemia injury in neural cells and brain with ischemia stroke. The role of miR‐134 in ischemic stroke remains poorly understood. The purpose of the current study was to investigate the effect of bone marrow–derived mesenchymal stem cells (BMSCs)‐derived exosomal miR‐134 on rat oligodendrocytes (OLs) apoptosis and its underlying mechanism of action. The results demonstrated that levels of miR‐134 in BMSCs‐exosome decreased but increased incaspase‐8 after oxygen‐glucose deprivation (OGD) treatment. Exosomal miR‐134 significantly inhibited apoptosis by decreasing caspase‐8 expression and activity in OGD‐treated group cultured with BMSCs‐exosome and OLs. In addition, the miR‐134 mimics decreased caspase‐8 expression in OGD‐treated OLs, whereas miR‐134 inhibitors exacerbated the changes in the expression of the procaspase‐8 and caspase‐8 cleaved product proteins caused by OGD. The caspase‐8 knockdown using caspase‐8 small interfering RNA decreased OLs apoptosis, reversing the improvements that the miR‐134 inhibited cells apoptosis by targeting caspase‐8. Taken together, these results demonstrated that BMSCs‐derived exosomes suppressed OLs apoptosis through exosomal miR‐134 by negatively regulating the caspase‐8‐dependent apoptosis pathway and may, therefore, be a novel potential therapeutic target for ischemic stroke treatment.
Neutrophil-to-lymphocyte ratio and mean platelet volume can be useful markers to predict sepsis in children

Objectives: Neutrophil-to-Lymphocyte Ratio (NLR) and Mean Platelet Volume (MPV) have been found to be useful indexes for the diagnosis of sepsis in adults. However, the knowledge of their roles and cut-off values in pediatric patients is limited. The primary objective of this study was to assess the ability of NLR and MPV to predict sepsis in children. A secondary aim was to evaluate the comparison of these parameters with C-reactive Protein (CRP). Methods: The study was conducted on pediatric patients, who had two or more of the following criteria were included in the study: tachycardia, tachypnea, temperature change, leukocytosis, or leukopenia for age. Patients were classified into sepsis and non-sepsis groups. The sepsis group was defined as the presence of two or more age specific Systemic Inflammatory Response Syndrome (SIRS) criteria and increased Procalcitonin (PCT) level (>0.5 ng/ml) Result: The median age of the study population was 18 (6-169) months. Two hundred-sixty four episodes of sepsis were recorded in 125 patients. Eighty two were classified as sepsis and 182 as non-sepsis. CRP level and MPV value were significantly higher in the sepsis group compared to non-sepsis group. The median CRP level was 47.8 mg/dl (10.2-119.5) in the sepsis group and 18.6 mg/dl (4.9-66.1) in the non-sepsis group (p=0.006). In the sepsis group, the median MPV value was 8.4 (7.6-9.5) and it was 7.8 (7.1-8.5) in the non-sepsis group (p=0.001). Significant correlations were found between the procalcitonin (PCT) and CRP level (p<0.001; r = 0.279), NLR (p=0.02; r = 0.186) and MPV (p<0.001; r = 0.243). MPV had the highest specificity for predicting sepsis (75.8%). The largest AUC was 0.629 with a cut-off value 8.5 for MPV, while the AUC was 0.557 with a cut-off value 1.97 for NLR and 0.606 with a cut-off value 38.9 for CRP. Conclusions: NLR and MPV values should alert clinicians to the possibility of sepsis and to initiate or change antibiotic treatment.
Surface Light Field Fusion

We present an approach for interactively scanning highly reflective objects with a commodity RGBD sensor. In addition to shape, our approach models the surface light field, encoding scene appearance from all directions. By factoring the surface light field into view-independent and wavelength-independent components, we arrive at a representation that can be robustly estimated with IR-equipped commodity depth sensors, and achieves high quality results.
Biofeedback for Everyday Stress Management: A Systematic Review

Background Mainly due to an increase in stress-related health problems and driven by recent technological advances in biosensors, microelectronics, computing platform, and human-computer interaction, ubiquitous physiological information will potentially transform the role of biofeedback in clinical treatment. Such technology is also likely to provide a useful tool for stress management in everyday life. The aim of this systematic review is to: 1) Classify biofeedback systems for stress management, with a special focus on biosensing techniques, bio-data computing approaches, biofeedback protocol, and feedback modality. 2) Review ways of evaluating approaches to biofeedback applications in terms of their effectiveness in stress management. Method A systematic literature search was conducted using keywords for “Biofeedback” and “Stress” within the following databases: PubMed, IEEE Xplore, ACM, and Scopus. Two independent reviewers were involved in selecting articles. Results We identified 103 studies published between 1990 and 2016, 46 of which met our inclusion criteria and were further analyzed. Based on the evidence reviewed, HRV, multimodal biofeedback, RSP, HR, and GSR appear to be the most common techniques for alleviating stress. Traditional screen-based visual displays remain the most common devices used for biofeedback display. Biofeedback applications are usually assessed by making both physiological and psychological measurements. Conclusions This review reveals several challenges related to biofeedback for everyday stress management, such as the facilitating user’s perception and interpretating the biofeedback information, the demand of ubiquitous biosensing and display technologies, and field evaluation in order to understand the use of biofeedback in everyday environments. We expect that various emerging HCI technologies could be used to address these challenges. New interaction designs as well as biofeedback paradigms can be further explored in order to for improve the accessibility, usability, comfort, engagement with, and user experience of biofeedback in everyday use.
Does Late Maturity Alpha-Amylase Impact Wheat Baking Quality?

Late maturity α-amylase (LMA) and pre-harvest sprouting (PHS) are both recognized as environmentally induced grain quality defects resulting from abnormally high levels of α-amylase. LMA is a more recently identified quality issue that is now receiving increasing attention worldwide and whose prevalence is now seen as impeding the development of superior quality wheat varieties. LMA is a genetic defect present in specific wheat genotypes and is characterized by elevated levels of the high pI TaAMY1 α-amylase, triggered by environmental stress during wheat grain development. TaAMY1 remains present in the aleurone through the harvest, lowering Falling Number (FN) at receival, causing a down-grading of the grain, often to feed grade, thus reducing the farmers’ income. This downgrading is based on the assumption within the grain industry that, as for PHS, a low FN represents poor quality grain. Consequently any wheat line possessing low FN or high α-amylase levels is automatically considered a poor bread wheat despite there being no published evidence to date, to show that LMA is detrimental to end product quality. To evaluate the validity of this assumption a comprehensive evaluation of baking properties was performed from LMA prone lines using a subset of tall non-Rht lines from a multi-parent advanced generation inter-cross (MAGIC) wheat population grown at three different sites. LMA levels were determined along with quality parameters including end product functionality such as oven spring, bread loaf volume and weight, slice area and brightness, gas cell number and crumb firmness. No consistent or significant phenotypic correlation was found between LMA related FN and any of the quality traits. This manuscript provides for the first time, compelling evidence that LMA has limited impact on bread baking end product functionality.
Molecular Recognition of Parallel G-quadruplex [d-(TTGGGGT)]4 Containing Tetrahymena Telomeric DNA Sequence by Anticancer Drug Daunomycin: NMR-Based Structure and Thermal Stability

The anticancer drug daunomycin exerts its influence by multiple strategies of action to interfere with gene functioning. Besides inhibiting DNA/RNA synthesis and topoisomerase-II, it affects the functional pathway of telomere maintenance by the telomerase enzyme. We present evidence of the binding of daunomycin to parallel-stranded tetramolecular [d-(TTGGGGT)]4 guanine (G)-quadruplex DNA comprising telomeric DNA from Tetrahymena thermophilia by surface plasmon resonance and Diffusion Ordered SpectroscopY (DOSY). Circular Dichroism (CD) spectra show the disruption of daunomycin dimers, suggesting the end-stacking and groove-binding of the daunomycin monomer. Proton and phosphorus-31 Nuclear Magnetic Resonance (NMR) spectroscopy show a sequence-specific interaction and a clear proof of absence of intercalation of the daunomycin chromophore between base quartets or stacking between G-quadruplexes. Restrained molecular dynamics simulations using observed short interproton distance contacts depict interaction at the molecular level. The interactions involving ring A and daunosamine protons, the stacking of an aromatic ring of daunomycin with a terminal G6 quartet by displacing the T7 base, and external groove-binding close to the T1–T2 bases lead to the thermal stabilization of 15 °C, which is likely to inhibit the association of telomerase with telomeres. The findings have implications in the structure-based designing of anthracycline drugs as potent telomerase inhibitors.
Stiff person syndrome with Anti‐GAD65 antibodies within the national veterans affairs health administration

Introduction: Stiff person syndrome (SPS) is a neurological disorder characterized by muscle rigidity primarily in the truncal muscles, commonly associated with autoantibodies to the glutamic acid‐decarboxylase 65 kD receptor (GAD65). There is limited epidemiological information on patients with SPS. Methods: We performed a retrospective case review using the National United States Veterans Affairs Health Administration electronic medical record system. We analyzed prevalence, demographics, disease characteristics, and treatment outcomes in SPS patients who were anti‐GAD65 antibody positive. Results: Fifteen patients met our criteria. Point prevalence was 2.06 per million, and period prevalence was 2.71 per million. Men to women ratio was 14:1. All patients benefitted from treatment with symptomatic antispasmodic agents. Ten of 15 patients received intravenous immunoglobulin, with a majority demonstrating stable or improved modified Rankin scores. Discussion: This investigation was a large North American epidemiological study of SPS with predominantly male patients. Symptomatic therapy was beneficial for most patients, with less clear sustained benefit of immunotherapy. Muscle Nerve 58:801–804, 2018
Improving motivation to change amongst individuals with eating disorders: A systematic review

OBJECTIVE People with eating disorders can have low motivation to change their eating disorder behaviors. Interventions aiming to enhance motivation to change have been increasingly advocated in their treatment. Questions remain regarding the strength of the evidence supporting the effectiveness of interventions that specifically focus on improving motivation. This review explored the evidence for improving motivation to change in eating disorders via clinical interventions. METHOD Searches of the published and unpublished literature were conducted by searching databases (PubMed, PsychInfo, Web of Science) and trial registries (WHO ICTRP), and by contacting authors. Studies were included if they investigated an intervention for eating disorder patients, included a pre-post outcome measure of motivation to change and were published in English. Risk of bias was also assessed. RESULTS Forty-two studies were included in the final review. Evidence was found to support the use of interventions to improve motivation to change, though it was unclear whether motivational interventions present a more effective option than approaches that do not exclusively or specifically focus on motivation. However, motivational interventions were identified as being more effective than low intensity treatments. Risk of bias in included studies was generally high. DISCUSSION Motivation was found to increase across treatments in general, whether or not the focus of the intervention was on enhancing motivation. It is unclear if interventions specifically targeting motivation to change provide additional benefit over and above established treatment approaches.
Inverted repeat structures are associated with essential and highly expressed genes on C. elegans autosome distal arms

Complementary sequences in cellular transcripts base-pair to form double-stranded RNA (dsRNA) structures. Because transposon-derived repeats often give rise to self-complementary sequences, dsRNA structures are prevalent in eukaryotic genomes, typically occurring in gene introns and untranslated regions (UTRs). However, the regulatory impact of double-stranded structures within genes is not fully understood. We used three independent methods to define loci in Caenorhabditis elegans predicted to form dsRNA and correlated these structures with patterns of gene expression, gene essentiality, and genome organization. As previously observed, dsRNA loci are enriched on distal arms of C. elegans autosomes, where genes typically show less conservation and lower overall expression. In contrast, we find that dsRNAs are associated with essential genes on autosome arms, and dsRNA-associated genes exhibit higher-than-expected expression and histone modification patterns associated with transcriptional elongation. Genes with significant repetitive sequence content are also highly expressed, and, thus, observed gene expression trends may relate either to dsRNA structures or to repeat content. Our results raise the possibility that as-yet-undescribed mechanisms promote expression of loci that produce dsRNAs, despite their well-characterized roles in gene silencing.
Peer Victimization in Children With ADHD: A Community-Based Longitudinal Study

Objectives: To investigate (a) whether children with ADHD experience higher levels of overt and relational peer victimization (PV) than children without ADHD and (b) child, family, and school predictors of PV in children with ADHD. Method: 173 children with ADHD and 199 non-ADHD controls were recruited through 43 Melbourne schools at mean age 7.3 years. Parent- and teacher-reported PV (Social Experience Questionnaire) data were collected at mean age 8.9 years. Potential child, family, and school predictors of PV were measured at baseline. Results: Children with ADHD experienced higher levels of PV than children without ADHD by both parent- and teacher-report. Child predictors accounted for the greatest variance in PV, and the strongest predictors of PV were teacher-reported conduct problems, and medication use. Conclusion: Children with ADHD are at higher risk of PV compared with non-ADHD controls. Recognizing and addressing PV is important to reduce additional impairment in children with ADHD.
Muscarinic M5 receptors trigger acetylcholine‐induced Ca2+ signals and nitric oxide release in human brain microvascular endothelial cells

Basal forebrain neurons control cerebral blood flow (CBF) by releasing acetylcholine (Ach), which binds to endothelial muscarinic receptors to induce nitric (NO) release and vasodilation in intraparenchymal arterioles. Nevertheless, the mechanism whereby Ach stimulates human brain microvascular endothelial cells to produce NO is still unknown. Herein, we sought to assess whether Ach stimulates NO production in a Ca2+‐dependent manner in hCMEC/D3 cells, a widespread model of human brain microvascular endothelial cells. Ach induced a dose‐dependent increase in intracellular Ca2+ concentration ([Ca2+]i) that was prevented by the genetic blockade of M5 muscarinic receptors (M5‐mAchRs), which was the only mAchR isoform coupled to phospholipase Cβ (PLCβ) present in hCMEC/D3 cells. A comprehensive real‐time polymerase chain reaction analysis revealed the expression of the transcripts encoding for type 3 inositol‐1,4,5‐trisphosphate receptors (InsP3R3), two‐pore channels 1 and 2 (TPC1–2), Stim2, Orai1–3. Pharmacological manipulation showed that the Ca2+ response to Ach was mediated by InsP3R3, TPC1–2, and store‐operated Ca2+ entry (SOCE). Ach‐induced NO release, in turn, was inhibited in cells deficient of M5‐mAchRs. Likewise, Ach failed to increase NO levels in the presence of l‐NAME, a selective NOS inhibitor, or BAPTA, a membrane‐permeant intracellular Ca2+ buffer. Moreover, the pharmacological blockade of the Ca2+ response to Ach also inhibited the accompanying NO production. These data demonstrate for the first time that synaptically released Ach may trigger NO release in human brain microvascular endothelial cells by stimulating a Ca2+ signal via M5‐mAchRs.
Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: a meta‐analysis

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second‐generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first‐generation antipsychotics, FGAs). As some reports questioned this notion, we meta‐analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head‐to‐head RCTs, including 32 FGA and 86 SGA arms, were meta‐analyzed, yielding 32 FGA‐SGA pairs and 35 SGA‐SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3‐7.8%) vs. 2.6% (95% CI: 2.0‐3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39‐0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28‐0.45, p<0.0001, number‐needed‐to‐treat, NNT=20). Meta‐regression showed no FGA dose effect on FGA‐SGA comparisons (Z=−1.03, p=0.30). FGA‐SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non‐clozapine SGAs in exploratory pairwise comparisons. SGA‐SGA comparisons confirmed the olanzapine advantage vs. non‐clozapine SGAs (RaR=0.66, 95% CI: 0.49‐0.88, p=0.006, k=17, NNT=100). This meta‐analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.