Miracle-dz/UniFAR-FTUs huggingface dataset:
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.
Rethinking Pose in 3D: Multi-stage Refinement and Recovery for Markerless Motion Capture

We propose a CNN-based approach for multi-camera markerless motion capture of the human body. Unlike existing methods that first perform pose estimation on individual cameras and generate 3D models as post-processing, our approach makes use of 3D reasoning throughout a multi-stage approach. This novelty allows us to use provisional 3D models of human pose to rethink where the joints should be located in the image and to recover from past mistakes. Our principled refinement of 3D human poses lets us make use of image cues, even from images where we previously misdetected joints, to refine our estimates as part of an end-to-end approach. Finally, we demonstrate how the high-quality output of our multi-camera setup can be used as an additional training source to improve the accuracy of existing single camera models.
Limited ERG11 Mutations Identified in Isolates of Candida auris Directly Contribute to Reduced Azole Susceptibility

Multiple Erg11 amino acid substitutions were identified in clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. auris ERG11 alleles that encoded for Y132F or K143R substitutions; however, expression of alleles encoding I466M, Y501H, or other clade-defined amino acid differences yielded susceptible MICs. ABSTRACT Multiple Erg11 amino acid substitutions were identified in clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. auris ERG11 alleles that encoded for Y132F or K143R substitutions; however, expression of alleles encoding I466M, Y501H, or other clade-defined amino acid differences yielded susceptible MICs. Similar to other Candida species, specific C. auris ERG11 mutations resulted directly in reduced azole susceptibility.
Beneficial Effects of Capparis Spinosa Honey on the Immune Response of Rats Infected with Toxoplasma Gundii

Objectives The Toxoplasma gondii (T. gondii) is an intracellular opportunistic protozoan parasite that infects approximately one-third of the human population worldwide. Honey has long been used for treatment of many diseases in folk medicine. Honey has exhibited significant anthelmintic, nematicidal and anti-protozoal activities. This study was conducted to investigate the immunological patterns in rats infected with T. gondii who were treated orally with supplemented 15% Capparis spinosa honey (Saudi Arabia) for a period of 28 days. Methods Immunoglobulin M, immunoglobulin G, and cytokines were detected by using enzyme-linked immunosorbent assays (ELISAs). In addition, the mortality and the morbidity rates were assessed. Results Oral administration of Capparis spinosa honey as a natural food additive was experimentally shown to increase the antibody titer; furthermore, compared with the rats in the control group, the levels of the sera cytokines (IFN-γ, IL-1 and IL-6) were consistently higher at day 7 post-infection in the infected rats treated with oral supplements of Capparis spinosa honey. Conclusion Orally administered supplements of Capparis spinosa honey increased both the antibody titer and the cytokines (IFN-γ, IL-1 and IL-6) levels in rats infected with T. gondii.
Inflammatory Determinants of Pregravid Obesity in Placenta and Peripheral Blood

Pre-pregnancy (pregravid) obesity has been linked to several adverse health outcomes for both mother and offspring. Complications during pregnancy include increased risk for gestational diabetes, hypertension, preeclampsia, placental abruption, and difficulties during delivery. Several studies suggest that these negative outcomes are mediated by heightened systemic inflammation as well as changes in placental development and function. However, the molecular mechanisms by which pregravid obesity affects these processes are poorly understood. In this study, we aimed to address this question by carrying out a comprehensive analysis of the systemic maternal immune system coupled with placental gene expression and microbial profiling at term delivery (11 lean and 14 obese). Specifically, we examined the impact of pregravid obesity on circulating cytokines, chemokine, adipokines, and growth factors using multiplex Luminex assay. Innate and adaptive immune cell frequencies and their cytokine production in response to stimuli were measured using flow cytometry. Finally, changes in placental transcriptome and microbiome were profiled using RNA- and 16S-sequencing, respectively. Pregravid obesity is characterized by insulin and leptin resistance, high levels of circulating inflammatory markers IL-6 and CRP, in addition to chemokine IL-8 (p < 0.01). Moreover, pregravid obesity was associated with lower frequency of naïve CD4+ T-cells (p < 0.05), increased frequency of memory CD4+ T-cells (p < 0.01), and a shift towards Th2 cytokine production (p = 0.05). Myeloid cells from the obese cohort produced higher levels of pro-inflammatory cytokines but lower levels of chemokines following TLR stimulation (p < 0.05). Lastly, pregravid obesity is associated with increased abundance of Bacteroides and changes in the expression of genes important for nutrient transport and immunity (FDR < 0.05). Collectively, these data indicate that pregravid obesity is associated with heightened systemic inflammation and of dysregulated nutrient transport in the placenta and provide insight into the basis of fetal reprogramming.
Defense Against Adversarial Attacks with Saak Transform

Deep neural networks (DNNs) are known to be vulnerable to adversarial perturbations, which imposes a serious threat to DNN-based decision systems. In this paper, we propose to apply the lossy Saak transform to adversarially perturbed images as a preprocessing tool to defend against adversarial attacks. Saak transform is a recently-proposed state-of-the-art for computing the spatial-spectral representations of input images. Empirically, we observe that outputs of the Saak transform are very discriminative in differentiating adversarial examples from clean ones. Therefore, we propose a Saak transform based preprocessing method with three steps: 1) transforming an input image to a joint spatial-spectral representation via the forward Saak transform, 2) apply filtering to its high-frequency components, and, 3) reconstructing the image via the inverse Saak transform. The processed image is found to be robust against adversarial perturbations. We conduct extensive experiments to investigate various settings of the Saak transform and filtering functions. Without harming the decision performance on clean images, our method outperforms state-of-the-art adversarial defense methods by a substantial margin on both the CIFAR-10 and ImageNet datasets. Importantly, our results suggest that adversarial perturbations can be effectively and efficiently defended using state-of-the-art frequency analysis.
Auditory Event-Related Potentials Associated With Music Perception in Cochlear Implant Users

A short review of the literature on auditory event-related potentials and mismatch negativities (MMN) in cochlear implant users engaged in music-related auditory perception tasks is presented. Behavioral studies that have measured the fundamental aspects of music perception in CI users have found that they usually experience poor perception of melody, pitch, harmony as well as timbre (Limb and Roy, 2014). This is thought to occur not only because of the technological and acoustic limitations of the device, but also because of the biological alterations that usually accompany deafness. In order to improve music perception and appreciation in individuals with cochlear implants, it is essential to better understand how they perceive music. As suggested by recent studies, several different electrophysiological paradigms can be used to reliably and objectively measure normal-hearing individuals' perception of fundamental musical features. These techniques, when used with individuals with cochlear implants, might contribute to determine how their peripheral and central auditory systems analyze musical excerpts. The investigation of these cortical activations can moreover give important information on other aspects related to music appreciation, such as pleasantness and emotional perception. The studies reviewed suggest that cochlear implantation alters most fundamental musical features, including pitch, timbre, melody perception, complex rhythm, and duration (e.g., Koelsch et al., 2004b; Timm et al., 2012, 2014; Zhang et al., 2013a,b; Limb and Roy, 2014). A better understanding of how individuals with cochlear implants perform on these tasks not only makes it possible to compare their performance to that of their normal-hearing peers, but can also lead to better clinical intervention and rehabilitation.
Detection of atrial fibrillation with a smartphone camera: first prospective, international, two-centre, clinical validation study (DETECT AF PRO)

Abstract Aims Early detection of atrial fibrillation (AF) is essential for stroke prevention. Emerging technologies such as smartphone cameras using photoplethysmography (PPG) and mobile, internet-enabled electrocardiography (iECG) are effective for AF screening. This study compared a PPG-based algorithm against a cardiologist’s iECG diagnosis to distinguish between AF and sinus rhythm (SR). Methods and results In this prospective, two-centre, international, clinical validation study, we recruited in-house patients with presumed AF and matched controls in SR at two university hospitals in Switzerland and Germany. In each patient, a PPG recording on the index fingertip using a regular smartphone camera followed by iECG was obtained. Photoplethysmography recordings were analysed using an automated algorithm and compared with the blinded cardiologist’s iECG diagnosis. Of 672 patients recruited, 80 were excluded mainly due to insufficient PPG/iECG quality, leaving 592 patients (SR: n = 344, AF: n = 248). Based on 5 min of PPG heart rhythm analysis, the algorithm detected AF with a sensitivity of 91.5% (95% confidence interval 85.9–95.4) and specificity of 99.6% (97.8–100). By reducing analysis time to 1 min, sensitivity was reduced to 89.9% (85.5–93.4) and specificity to 99.1% (97.5–99.8). Correctly classified rate was 88.8% for 1-min PPG analysis and dropped to 60.9% when the threshold for the analysed file was set to 5 min of good signal quality. Conclusion This is the first prospective clinical two-centre study to demonstrate that detection of AF by using a smartphone camera alone is feasible, with high specificity and sensitivity. Photoplethysmography signal analysis appears to be suitable for extended AF screening. Clinical trial registration ClinicalTrials.gov, number NCT02949180, https://clinicaltrials.gov/ct2/show/NCT02949180.
Exploring the role of context on the existing evidence for reconsolidation of episodic memory

ABSTRACT Recent research has provided evidence for memory modifications when a post-reactivation treatment (e.g., drugs, new learning) interferes with the memory re-stabilisation (reconsolidation) process. This finding contradicts the long-standing consolidation theory and has high practical and theoretical implications. With an object-learning paradigm, it was shown that episodic memory is highly susceptible to interfering material presented after its reactivation [Hupbach, A. , Gomez, R. , Hardt, O. , & Nadel, L. (2007). Reconsolidation of episodic memories: A subtle reminder triggers integration of new information. Learning & Memory, 14, 47–53. doi:10.1101/lm.365707]. The reactivation of a learned list (List 1) before a second learned list (List 2) led to intrusion errors from List 2 when trying to recall List 1, but not vice-versa. Their work has been widely cited and their findings have been explained according to reconsolidation theory. For the first time, we systematically explored the role of retrieval context as an alternative explanation for Hupbach’s results. Our results showed that the intrusion effect occurs independently of the retrieval context (Experiment 1). Additionally, even when the intrusion rate probability is increased (i.e., List 1 memory test is performed in the List 2 learning context), the groups that did not reactivate the original list did not commit intrusion errors (Experiment 2). In sum, we found that the intrusion effect critically depends on the presence of reactivation, discarding alternative interpretations of the results.
The Impact of Salpingectomy on Anti-Mullerian Hormone Levels and Ovarian Response of In Vitro Fertilization Patients.

BACKGROUND Laparoscopic salpingectomy is strongly related to successful in vitro fertilization (IVF) treatments. OBJECTIVES To compare the ovarian reserve, including anti-mullerian hormone (AMH) levels, in patients who underwent salpingectomy before IVF to IVF patients who had not been salpingectomized. METHODS In this retrospective study, medical records of women who were treated by the IVF unit at our institute were reviewed. We retrieved demographic data, surgical details, and data regarding the ovarian reserve. Details of 35 patients who were treated by IVF after salpingectomy were compared to 70 IVF patients with no history of salpingectomy treatment. Nine women underwent IVF treatment before and after having salpingectomy, and their details were included in both groups. RESULTS The levels of AMH, follicular stimulating hormone (FSH), estradiol, and progesterone were not significantly different in the groups. The antral follicular count (AFC), number of oocytes retrieved, amount of gonadotropin administered for ovarian stimulation, and number of embryos transferred (ET) were also not significantly different. CONCLUSIONS Salpingectomy does not seem to affect ovarian reserve in IVF patients.
Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome

ABSTRACT Background: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections. Objectives: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients. Methods: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively. Results: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described. Conclusion: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.
A new dynamic correlation algorithm reveals novel functional aspects in single cell and bulk RNA-seq data

Dynamic correlations are pervasive in high-throughput data. Large numbers of gene pairs can change their correlation patterns in response to observed/unobserved changes in physiological states. Finding changes in correlation patterns can reveal important regulatory mechanisms. Currently there is no method that can effectively detect global dynamic correlation patterns in a dataset. Given the challenging nature of the problem, the currently available methods use genes as surrogate measurements of physiological states, which cannot faithfully represent true underlying biological signals. In this study we develop a new method that directly identifies strong latent dynamic correlation signals from the data matrix, named DCA: Dynamic Correlation Analysis. At the center of the method is a new metric for the identification of pairs of variables that are highly likely to be dynamically correlated, without knowing the underlying physiological states that govern the dynamic correlation. We validate the performance of the method with extensive simulations. We applied the method to three real datasets: a single cell RNA-seq dataset, a bulk RNA-seq dataset, and a microarray gene expression dataset. In all three datasets, the method reveals novel latent factors with clear biological meaning, bringing new insights into the data.
Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein 180L Single-Nucleotide Polymorphism Is Associated With Susceptibility to Recurrent Pneumococcal Lower Respiratory Tract Infections in Children

Lower respiratory tract infections (LRTI) are often caused by Streptococcus pneumoniae (Spn) and can be recurrent in 8% of children older than 2 years of age. Spn is recognized by pattern-recognition receptors (PRRs) of the innate immune system, in particular toll-like receptors (TLRs) 2 and 4. To assess whether a defect somewhere along this TLR signaling pathway increases susceptibility to recurrent pneumococcal LRTI, we conducted a prospective case–control study with 88 healthy individuals and 45 children with recurrent LRTI aged 2–5 years old. We examined cell surface expression of TLR2 and TLR4, as well as eight genetic variants of these receptors or associated co-receptors TLR1 and TLR6. Interleukin-6 production was measured after whole blood stimulation assays with specific agonists and heat-killed Spn. Our findings reveal that single-nucleotide polymorphisms within toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) alone or in combination with TLR1 N248S, TLR1 I602S, or TLR6 S249P polymorphisms contributes to various degree of susceptibility to recurrent pneumococcal LRTI in children by modulating the inflammatory response. In that respect, carriage of the TIRAP S180L heterozygous trait increases the likelihood to protect against pneumococcal LRTI, whereas children carrying the mutant homozygous TIRAP 180L polymorphism might be more likely susceptible to recurrent pneumococcal LRTI.
code2seq: Generating Sequences from Structured Representations of Code

The ability to generate natural language sequences from source code snippets has a variety of applications such as code summarization, documentation, and retrieval. Sequence-to-sequence (seq2seq) models, adopted from neural machine translation (NMT), have achieved state-of-the-art performance on these tasks by treating source code as a sequence of tokens. We present ${\rm {\scriptsize CODE2SEQ}}$: an alternative approach that leverages the syntactic structure of programming languages to better encode source code. Our model represents a code snippet as the set of compositional paths in its abstract syntax tree (AST) and uses attention to select the relevant paths while decoding. We demonstrate the effectiveness of our approach for two tasks, two programming languages, and four datasets of up to $16$M examples. Our model significantly outperforms previous models that were specifically designed for programming languages, as well as state-of-the-art NMT models. An interactive online demo of our model is available at this http URL Our code, data and trained models are available at this http URL
Morphological and molecular identification of three new species of Tomentella from Finland

ABSTRACT Three new species of Tomentella (Thelephorales) from Finland, T. globosa, T. lammiensis, and T. longisterigmata, are described and illustrated with morphological characteristics and nuc rDNA ITS1-5.8S-ITS2 sequences. T. globosa is characterized by mucedinoid, pale to dark brown basidiocarps adherent to the substrate, generative hyphae with clamps and rarely with simple septa, and echinulate, globose basidiospores (echinuli up to 1.5 μm long). T. lammiensis is characterized by mucedinoid, oxide yellow to golden brown basidiocarps adherent to the substrate, generative hyphae with clamps and rarely with simple septa, and echinulate, ellipsoid, triangular, or lobbed basidiospores (echinuli up to 2 μm long). T. longisterigmata is characterized by mucedinoid, dark brown to chestnut basidiocarps separable from the substrate, generative hyphae clamped and rarely with simple septa, the long basidial sterigmata (7–11 μm long), and echinulate, globose basidiospores (echinuli up to 2 μm long). An absence of rhizomorphs and cystidia is their common morphological feature. Molecular analyses by maximum likelihood, maximum parsimony, and Bayesian analyses confirm the phylogenetic position of these three new species. The discriminating characters of these new species and their closely related species are discussed in this study, and a key to the species from Finland is provided.
Cancer-Specific Stress and Trajectories of Psychological and Physical Functioning in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia.

Background Chronic lymphocytic leukemia is the most prevalent adult leukemia. The disease is incurable with a cycling of treatment and relapse common. Little is known about the psychological and physical functioning of patients with relapsed/refractory chronic lymphocytic leukemia. Cancer-specific stress is an important individual difference variable that predicts psychological and physical outcomes. Purpose To examine cancer-specific stress at treatment initiation as a predictor of psychological and physical functioning trajectories in patients with relapsed/refractory chronic lymphocytic leukemia during the first 5 months of treatment. Methods Patients with relapsed/refractory chronic lymphocytic leukemia (N = 152) enrolled in a phase II clinical trial completed self-report measures at treatment initiation (baseline), 1, 2, and 5 months of treatment. Cancer-specific stress at baseline was examined as a predictor of psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems, physical health quality of life), controlling for demographic and treatment variables. Results Using multilevel modeling, higher baseline cancer-specific stress was related to worse psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems) at baseline and more rapid improvements during the next 5 months. Despite these improvements, higher baseline cancer-specific stress remained associated with poorer 5-month psychological, though not physical, functioning. Conclusions Findings suggest cancer-specific stress at treatment initiation may be a risk factor for poorer psychological functioning during treatment for patients with relapsed/refractory chronic lymphocytic leukemia.