Miracle-dz/UniFAR-FTUs huggingface dataset:
Short‐Term Memory Span and Cross‐Modality Integration in Younger and Older Adults With and Without Autism Spectrum Disorder

This study tested whether adults with autism spectrum disorder (ASD) show the same pattern of difficulties and absence of age‐related differences in short‐term memory (STM) as those that have been reported in episodic long‐term memory (LTM). Fifty‐three adults with ASD (age range: 25–65 years) were compared to 52 age‐, biological sex‐, and intelligence‐matched typically developing (TD; age range: 21–67 years) adults on three STM span tasks, which tested STM performance for letters (Verbal), grid locations (Visuospatial), or letters in grid locations (Multimodal). A subsample of 34 TD and 33 ASD participants ranging in age from 25 to 64 years completed a fourth Multimodal Integration task. We also administered the Color Trails Test as a measure of executive function. ASD participants' accuracy was lower than that of the TD participants on the three span tasks (Cohen's d: 0.26–0.50). The Integration task difference was marginally significant (p = .07) but had a moderate effect size (Cohen's d = 0.50). Regression analyses confirmed reduced STM performance only for older TD participants. Analyses also indicated that executive processes played a greater role in the ASD group's performance. The demonstration of similar difficulties and age‐related patterning of STM in ASD to those documented for LTM and the greater recruitment of executive processes by older ASD participants on the Integration task suggest a compensatory role of frontal processes both as a means of achieving undiminished task performance and as a possible protection against older age cognitive decline in ASD. Longitudinal research is needed to confirm this. Autism Res 2020, 13: 1970‐1984. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.
New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The intricate NAFLD pathogenesis is summarized by the multiple-hits hypothesis, which combines all the environmental and genetic factors that promote the development of NAFLD into a single scenario. Among these, bacterial lipopolysaccharides (LPS) are derived from the overgrowth of Gram-negative bacteria and translocated mainly as a consequence of enhanced intestinal permeability. Furthermore, oxidative stress is increased in NAFLD as a consequence of reactive oxygen species (ROS) overproduction and a shortage of endogenous antioxidant molecules, and it is promoted by the interaction between LPS and the Toll-like receptor 4 system. Interestingly, oxidative stress, which has previously been described as being overexpressed in cardiovascular disease, could represent the link between LPS and the increased cardiovascular risk in NAFLD subjects. To date, the only effective strategy for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH) is the loss of at least 5% body weight in overweight and/or obese subjects. However, the dose-dependent effects of multispecies probiotic supplementation on the serum LPS level and cardiometabolic profile in obese postmenopausal women were demonstrated. In addition, many antibiotics have regulatory effects on intestinal microbiota and were able to reduce serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor alpha (TNF-α) in NASH animal models. Regarding the oxidant status, a Mediterranean diet has been reported to reduce oxidant stress, while vitamin E at high daily dosages induced the resolution of NASH in 36% of treated patients. Silymarin had the positive effect of reducing transaminase levels in NAFLD patients and long-term treatment may also decrease fibrosis and slow liver disease progression in NASH. Finally, the influence of nutraceuticals on gut microbiota and oxidant stress in NAFLD patients has not yet been well elucidated and there are insufficient data either to support or refuse their use in these subjects.
Degeneration of gray and white matter differs between hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD: a longitudinal MRI − PET multimodal study

Abstract Objective [18F]-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) imaging and magnetic resonance imaging (MRI) of brain in ALS patients with frontotemporal lobe dementia (ALS-FTD) reveal hypometabolism and hypermetabolism, as well as gray matter (GM) and white matter (WM) abnormalities in different brain regions, respectively. Hypometabolism arising from neuronal dysfunction or loss is the most recognized pathophysiologic change in neurodegeneration, whereas mechanisms underlying hypermetabolism remain unclear. We hypothesize that hypometabolic and hypermetabolic brain regions in ALS-FTD represent differential degeneration of GM and WM structures, as revealed by co-registered MRI in a two time-point longitudinal multimodal study. Methods: A 69-year-old female with ALS-FTD underwent 18F-FDG PET, diffusion tensor imaging (DTI), and T1-weighted MRI at baseline (15 months after symptom onset), and 20.4 months later. Cerebral glucose metabolism rate, cortical thickness, cortical area, and WM network changes were measured longitudinally. Results and conclusion: The patient had symptoms and signs of bulbar-onset upper motor neuron (UMN)-predominant ALS with language and behavioral dysfunction. Evaluation at baseline showed bulbar dysfunction, and impaired language and executive function. At follow-up, worsened bulbar and other motor functions, and prominent FTD both reflected significant progression. Cortical thickness and surface area showed differential involvement in the hypometabolic and hypermetabolic regions. WM connections from frontal regions to other brain regions were completely absent by graph theory-based network analysis when compared to temporal regions indicating prominent frontal lobe degeneration. Structural neuroimaging reveals different patterns of GM and WM involvement in the hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD.
TMEM79/MATTRIN defines a pathway for Frizzled regulation and is required for Xenopus embryogenesis

Wnt signaling through the Frizzled (FZD) family of serpentine receptors is essential for embryogenesis and homeostasis, and stringent control of the FZD protein level is critical for stem cell regulation. Through CRISPR/Cas9 genome-wide screening in human cells, we identified TMEM79/MATTRIN, an orphan multi-span transmembrane protein, as a specific inhibitor of Wnt/FZD signaling. TMEM79 interacts with FZD during biogenesis and promotes FZD degradation independent of ZNRF3/RNF43 ubiquitin ligases (R-spondin receptors). TMEM79 interacts with ubiquitin-specific protease 8 (USP8), whose activating mutations underlie human tumorigenesis. TMEM79 specifically inhibits USP8 deubiquitination of FZD, thereby governing USP8 substrate specificity and promoting FZD degradation. Tmem79 and Usp8 genes have a pre-bilaterian origin, and Tmem79 inhibition of Usp8 and Wnt signaling is required for anterior neural development and gastrulation in Xenopus embryos. TMEM79 is a predisposition gene for Atopic dermatitis, suggesting deregulation of Wnt/FZD signaling a possible cause for this most common yet enigmatic inflammatory skin disease.
LDHB inhibition induces mitophagy and facilitates the progression of CSFV infection

ABSTRACT Cellular metabolism caters to the energy and metabolite needs of cells. Although the role of the terminal metabolic enzyme LDHB (lactate dehydrogenase B) in the glycolysis pathway has been widely studied in cancer cells, its role in viral infection is relatively unknown. In this study, we found that CSFV (classical swine fever virus) infection reduces pyruvate levels while promotes lactate release in pigs and in PK-15 cells. Moreover, using a yeast two-hybrid screening system, we identified LDHB as a novel interacting partner of CSFV non-structural protein NS3. These results were confirmed via co-immunoprecipitation, glutathione S-transferase and confocal assays. Furthermore, knockdown of LDHB via interfering RNA induced mitochondrial fission and mitophagy, as detected reduced mitochondrial mass. Upon inhibition of LDHB, expression of the mitophagy proteins TOMM20 and VDAC1 decreased and the ubiquitination of MFN2, a mitochondrial fusion mediator, was promoted. In addition, a sensitive dual ﬂuorescence reporter (mito-mRFP-EGFP) was utilized to analyze the delivery of autophagosomes to lysosomes in LDHB inhibition cells. Furthermore, LDHB inhibition promoted NFKB signaling, which was regulated by mitophagy; meanwhile, infection with CSFV negated these NFKB anti-viral responses. Inhibition of LDHB also inhibited apoptosis, providing an environment conducive to persistent viral infection. Finally, we demonstrated that LDHB inhibition promoted CSFV growth via mitophagy, whereas its overexpression decreased CSFV replication. Our data revealed a novel mechanism through which LDHB, a metabolic enzyme, mediates CSFV infection, and provides new avenues for the development of anti-viral strategies.Abbreviations: 3-MA:3-methyladenine; CCCP:carbonyl cyanide 3-chlorophenylhydrazone; CCK-8:cell counting kit-8; CSFV:classical swine fever virus; DAPI:4′,6-diamidino-2-phenylindole; DMSO:dimethyl sulfoxide; EGFP:enhanced green fluorescent protein; FBS:fetal bovine serum; FITC:fluorescein isothiocyanate; GST:glutathione-S-transferase; HCV:hepatitis C virus; IFN:interferon; LDH:lactate dehydrogenase; MAP1LC3/LC3:microtubule associated protein 1 light chain 3; MFN2:mitofusin 2; MOI:multiplicity of infection; NFKB:nuclear factor kappa B subunit 1; NFKBIA:nuclear factor inhibitor alpha; NS3:nonstructural protein 3; NKIRAS2:NFKB inhibitor interacting Ras like 2; PRKN:parkin E3 ubiquitin protein ligase; PBS:phosphate-buffered saline; qRT-PCR:real-time quantitative reverse transcriptase polymerase chain reaction; RELA:RELA proto-oncogene, NF-kB subunit; shRNA: short hairpin RNA; siRNA: small interfering RNA; TCID50:50% tissue culture infectious doses; TEM:transmission electron microscopy; TNF:tumor necrosis factor; TOMM20:translocase of outer mitochondrial membrane 20; VDAC1:voltage dependent anion channel 1.
Early-life adversities and adult attachment in depression and alexithymia

Abstract Alexithymia is a personality construct characterized by difficulties in identifying and verbalizing feelings, a restricted imagination, and an externally oriented thinking style. As alexithymia shows marked overlap with depression, its independent nature as a personality construct is still being debated. The etiology of alexithymia is unknown, although childhood emotional neglect and attachment formation are thought to play important roles. In the FinnBrain Birth Cohort Study, experiences of early-life adversities (EA) and childhood maltreatment (CM) were studied in a sample of 2,604 men and women. The overlap and differences between depression and alexithymia were investigated by comparing their associations with EA types and adult attachment style. Alexithymia was specifically associated with childhood emotional neglect (odds ratio (OR) 3.8, p < . 001), whereas depression was related to several types of EA. In depression co-occurring with alexithymia, there was a higher prevalence of emotional neglect (81.3% vs. 54.4%, p < .001), attachment anxiety (t = 2.38, p = .018), and attachment avoidance (t = 4.03, p < .001). Early-life adversities were markedly different in the alexithymia group compared to those suffering from depression, or healthy controls. Depression with concurrent alexithymia may represent a distinct subtype, specifically associated with childhood experiences of emotional neglect, and increased attachment insecurity compared to non-alexithymic depression.
NSAIDs as a Drug Repurposing Strategy for Biofilm Control

Persistent infections, usually associated with biofilm-producing bacteria, are challenging for both medical and scientific communities. The potential interest in drug repurposing for biofilm control is growing due to both disinvestment in antibiotic R&D and reduced efficacy of the available panel of antibiotics. In the present study, the antibacterial and antibiofilm activities of four non-steroidal anti-inflammatory drugs (NSAIDs), piroxicam (PXC), diclofenac sodium (DCF), acetylsalicylic acid (ASA) and naproxen sodium (NPX) were evaluated against Escherichia coli and Staphylococcus aureus. The minimum inhibitory/bactericidal concentrations (MICs and MBCs) and the dose–response curves from exposure to the selected NSAIDs were determined. MICs were found for PXC (800 μg/mL) and ASA (1750 μg/mL) against E. coli, and for DCF (2000 μg/mL) and ASA (2000 μg/mL) against S. aureus. No MBCs were found (>2000 μg/mL). The potential of NSAIDs to eradicate preformed biofilms was characterized in terms of biofilm mass, metabolic activity and cell culturability. Additionally, the NSAIDs were tested in combination with kanamycin (KAN) and tetracycline (TET). ASA, DCF and PXC promoted significant reductions in metabolic activity and culturability. However, only PXC promoted biofilm mass removal. Additive interactions were obtained for most of the combinations between NSAIDs and KAN or TET. In general, NSAIDs appear to be a promising strategy to control biofilms as they demonstrated to be more effective than conventional antibiotics.
Biomolecules and Electrochemical Tools in Chronic Non-Communicable Disease Surveillance: A Systematic Review

Over recent three decades, the electrochemical techniques have become widely used in biological identification and detection, because it presents optimum features for efficient and sensitive molecular detection of organic compounds, being able to trace quantities with a minimum of reagents and sample manipulation. Given these special features, electrochemical techniques are regularly exploited in disease diagnosis and monitoring. Specifically, amperometric electrochemical analysis has proven to be quite suitable for the detection of physiological biomarkers in monitoring health conditions, as well as toward the control of reactive oxygen species released in the course of oxidative burst during inflammatory events. Besides, electrochemical detection techniques involve a simple and swift assessment that provides a low detection-limit for most of the molecules enclosed biological fluids and related to non-transmittable morbidities.
TBK1/IKKε Negatively Regulate LPS-Induced Neutrophil Necroptosis and Lung Inflammation.

Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. Cell necroptosis features receptor-interacting protein (RIPK) 1 activation and necroptosome formation. This leads to loss of plasma membrane integrity, the release of cell contents into the extracellular space, and subsequent increased inflammation. Here we report an intra-PMN mechanism of negative regulation of necroptosis mediated through TBK1/IKKε. Using an in vivo mouse model of intratracheal injection (i.t.) of LPS and in vitro LPS stimulation of mouse PMN, we found that LPS-TLR4 signaling in PMNs activates and phosphorylates TBK1 and IKKε, which in turn suppress LPS-induced formation of the RIPK1-RIPK3-MLKL (necrosome) complex. TBK1 dysfunction by knockdown or inhibitor significantly increases the phosphorylation of RIPK1 (∼67%), RIPK3 (∼68%), and MLKL (∼50%) and promotes RIPK1-RIPK3 and RIPK3-MLKL interactions and increases PMN necroptosis (∼83%) in response to LPS, with subsequent augmented lung inflammation. These findings suggest that the LPS-TLR4-TBK1 axis serves as a negative regulator for PMN necroptosis and might be a therapeutic target for modulating PMN death and inflammation.
Physiological and oxidative stress responses to intermittent hypoxia training in Sprague Dawley rats

Abstract Aim Rapid ascent to high altitude and inability to acclimatize lead to high-altitude illnesses. Intermittent hypoxia (IH) conditioning has been hypothesized as a non-pharmacological strategy aiming to improve adaptive responses during high altitude ascent. In the recent years, IH training (IHT) has become increasingly popular among recreational and professional athletes owing to its ability to mitigate high altitude related problems. This study aimed at exploring the role of IHT in altitude acclimatization. Methods Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO2 under normobaric conditions. To assess the effect of IHT in hypoxic acclimatization, animals were further exposed to extreme hypoxia (EH) at 8% FiO2. Oxygen saturation (SpO2), respiratory rate and heart rate were recorded during the exposure. Oxidative stress (ROS, MDA, and 4-HNE) and histopathological examinations were studied in the lung tissue sections. Hypoxia biomarkers, HIF-1α, EPO, VEGF, and BPGM were evaluated through western blotting in the lung tissue. Results Assessment of the IHT showed that SpO2 levels were found to be higher in the IH trained rats with a statistical difference of p < 0.01 in the first hour of hypoxia exposure as compared to the untrained rats. There was a significantly higher (p < 0.001) generation of ROS and MDA in the untrained rats as compared to the trained rats. Lipid peroxidation markers and systemic inflammatory marker were found to be expressed at much higher level in the untrained rats. There was a higher expression of HIF-1α (1.24-fold ↑), VEGF (1.14-fold ↑) and decrease in EPO (1.43-fold ↓) in the untrained rats as compared to trained rats. Conclusions Preconditioning with IHT resulted in the reduction in hypoxia induced oxidative stress during extreme hypoxia exposure and thus, maintaining redox balance as well as adjustment in the physiological changes in rats.
Genotoxicity as a toxicologically relevant endpoint to inform risk assessment: A case study with ethylene oxide

The purpose of the present investigation is to analyze the in vivo genotoxicity dose–response data of ethylene oxide (EO) and the applicability of the derived point‐of‐departure (PoD) values when estimating permitted daily exposure (PDE) values. A total of 40 data sets were identified from the literature, and benchmark dose analyses were conducted using PROAST software to identify a PoD value. Studies employing the inhalation route of exposure and assessing gene or chromosomal mutations and chromosomal damage in various tissues were considered the most relevant for assessing risk from EO, since these effects are likely to contribute to adverse health consequences in exposed individuals. The PoD estimates were screened for precision and the values were divided by data‐derived adjustment factors. For gene mutations, the lowest PDE was 285 parts per trillion (ppt) based on the induction of lacI mutations in the testes of mice following 48 weeks of exposure to EO. The corresponding lowest PDE value for chromosomal mutations was 1,175 ppt for heritable translocations in mice following 8.5 weeks of EO exposure. The lowest PDE for chromosomal aberrations was 238 ppt in the mouse peripheral blood lymphocytes following 48 weeks of inhalation exposure. The diverse dose–response data for EO‐induced genotoxicity enabled the derivation of PoDs for various endpoints, tissues, and species and identified 238 ppt as the lowest PDE in this retrospective analysis.
Impact of Almond Variety on “Amaretti” Cookies as Assessed through Image Features Modeling, Physical Chemical Measures and Sensory Analyses

In the present study, the influence of almond variety on color, chemical, physical and sensory characteristics of “amaretti” cookies during the shelf life, was assessed. Four varieties were chosen for the study, two of which were local (Cossu, Arrubia) and two widely cultivated (Tuono, Texas). Almonds have been characterized in the content of proteins, crude fat, amygdalin and fatty acids profile. The evolution of the characteristics during the shelf life hasbeen measured through image data modeling, texture, physical chemical and sensory analyses. Data were then treated with a multivariate approach performing a PCA. Image analysis and fitting on log normal and powerlaw functions highlighted the influence of the variety on the total area affected by surface breakages, and on the distribution of the cracking surfaces dimension classes. Texture parameters (crust hardness, thickness and work of deformation) were negatively correlated to moisture content. Sensory profile confirmed the differences in tactile features measured through instrumental texture, while slight to no differences were found in odor profile. Consumer test showed an higher acceptability for Arrubia, Texas and Tuono samples throughout the shelf life, while Cossu samples were less accepted. Overall, the choice of almond variety influences product features and liking of almond products, therefore it represents an important phase to direct the choice of both farmers and confectionery manufacturers.
Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.