Miracle-dz/UniFAR-FTUs huggingface dataset:
N-palmitoyl-D-glucosamine, A Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.
Electrospun copper oxide nanofibers for H2S dosimetry

We present the preparation and characterization of a novel copper(II)oxide (CuO) nanofiber based sensor with very high sensitivity and selectivity to hydrogen sulfide (H2S). The working principle is based on the phase transition of semiconducting p‐type CuO to strongly degenerated p‐type copper sulfide (CuS) with metallic conductivity. Electrospun polymer fiber networks of polyvinyl butyrate (PVB) and Cu(NO3)2 were attached on standard gas sensing substrates and calcined to CuO at 600 °C in ambient air for 24 h. Continuous exposure to H2S (0.1–5 ppm) as well as a sequence of 1 ppm H2S pulses result in a dosimeter type behavior of the nanofiber sensors. Triggered by a certain dose (gas concentration multiplied by time) a steep conductance increase of the sensitive layer over several orders of magnitude is observed. After reaching this percolation threshold only small conductance changes were observed. These fiber based sensors show a remarkably high specificity, there is no response to carbon monoxide, hydrogen, and methane at 160 °C. The fiber network can be regenerated by raising the operating temperature to 350 °C for 30 min in absence of H2S.
In Vitro and In Vivo Characterization of MCT1 Inhibitor AZD3965 Confirms Preclinical Safety Compatible with Breast Cancer Treatment

Simple Summary The vast majority of tumors originate in tissues that use different substrates and oxygen to produce energy. However, tumors are disorganized structurally and functionally, which creates areas where oxygen and nutrients are poorly available. To survive and proliferate, cancer cells adapt by switching their metabolism to lactic fermentation. Their fate is further optimized by intercellular cooperation, but this creates a weakness that can be exploited therapeutically. Indeed, AZD3965 is a new drug currently tested in clinical trials that inhibits a cooperation based on lactate swapping for glucose between fermenting and respiring cells. It inhibits lactate transporter monocarboxylate transporter 1. Here, using malignant and nonmalignant cells representative of the breast tissue and several behavioral tests in mice, we establish that AZD3965 is safe for therapeutic use against cancer. The only side effect that we detected was a short-term memory retention defect that transiently perturbed the orientation of mice in space. Abstract To survive and proliferate in solid tumors, cancer cells adapt and evolve rapidly in microenvironments where oxygen and substrate bioavailability fluctuates over time and space. This creates metabolic heterogeneity. Cancer cells can further cooperate metabolically, for example by swapping glycolytic end-product lactate for blood-borne glucose. This type of cooperation can be targeted therapeutically, since transmembrane lactate exchanges are facilitated by lactate-proton symporters of the monocarboxylate (MCT) family. Among new drugs, AZD3965 is a first-in-class selective MCT1 inhibitor currently tested in Phase I/II clinical trials for patients with different types of cancers. Because MCT1 can function bidirectionally, we tested here whether and how malignant and nonmalignant cells adapt their metabolism and MCT repertoire when AZD3965 inhibits either lactate import or export. Using breast-associated malignant and nonmalignant cell lines as models, we report that AZD3965 is not directly cytotoxic. In the presence of glucose and glutamine, oxidative cells can survive when lactate uptake is blocked, and proliferating cells compensate MCT1 inhibition by overexpressing MCT4, a specialized facilitator of lactate export. Phenotypic characterization of mice focusing on metabolism, muscle and brain physiology found partial and transient memory retention defect as sole consequence of MCT1 inhibition by AZD3965. We therefore conclude that AZD3965 is compatible with anticancer therapy.
Clot Meniscus Sign: An Angiographic Clue for Choosing between Stent Retriever and Contact Aspiration in Acute Basilar Artery Occlusion

BACKGROUND AND PURPOSE: The efficacy of mechanical thrombectomy methods may differ depending on the characteristics of the occlusion. The purpose of this study was to compare the recanalization efficacy and treatment outcome of a stent retriever versus contact aspiration in patients with acute basilar artery occlusion according to the angiographic characteristics of the occlusion. MATERIALS AND METHODS: One hundred sixty-one patients with acute basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed. A stent retriever was compared with contact aspiration thrombectomy according to the clot meniscus sign, defined as a meniscoid/tram-track-like sidewall contrast opacification of the thrombus. A propensity score matching analysis was performed. Clinical/angiographic characteristics and treatment and clinical outcomes were compared. RESULTS: Overall, a stent retriever (n = 118) and contact aspiration (n = 43) did not show significant differences in the successful recanalization (82.2% versus 86.0%) and good clinical outcome rates (32.2% versus 39.5%). In patients with the positive meniscus sign, contact aspiration was associated with shorter procedural time (44 versus 26 minutes, P = .018), a lower number of passes (2 versus 1, P = .041), a higher complete recanalization rate (58.8% versus 85.7%, P = .021), and a higher rate of first-pass effect (27.9% versus 53.6%, P = .031) compared with a stent retriever. After propensity score matching, contact aspiration was associated with higher complete recanalization rates (59.3% versus 85.7%, P = .033). No significant differences in the outcomes were noted between a stent retriever and contact aspiration in patients negative for the meniscus sign. CONCLUSIONS: The efficacy of the mechanical thrombectomy techniques may differ according to the angiographic characteristics of occlusion in patients with basilar artery occlusion. Contact aspiration may be more effective in terms of recanalization compared with a stent retriever in patients with the clot meniscus sign.
Hybrid design evaluating new biomarkers when there is an existing screening test

Development of cancer screening biomarkers usually follows the Early Detection Research Network 5‐Phase guideline in Pepe et al. A key feature of this guide is that the phased development follows a sequential order, moving to the next phase only when the current phase study is complete and has met its target performance. Motivated by a newly funded Newly onset Diabetes cohort study, we propose a design evaluating new biomarkers to discriminate between cases and controls in the presence of an existing screening test. The proposed design achieves two goals: (1) avoiding bias in estimating sensitivity or specificity in predicting cancer at a given time period prior to clinical diagnosis, using data from both screening detected cancers in Phase IV study and clinically diagnosed cancers in Phase III study; and (2) building a panel with biomarkers for Phase III and IV studies based on all data. A simulation study shows that the proposed design outperforms both a conventional method using data in Phase III arm only and a naive method using data in Phase III and IV arms ignoring the difference between the time of screening the detected cancer and the time of clinical diagnosis. The proposed design yields a smaller standard error of the estimation and increases the statistical power to confirm biomarker performance. This proposed method has the potential to shorten the cancer screening biomarker development process, use resources more effectively, and bring benefits to patients quickly.
Does the clinical utility of self-disclosure of stuttering transcend culturally and linguistically diverse populations?

Abstract Purpose: Research suggests that self-disclosure can improve listeners’ perceptions of stuttering; however, it is unknown whether the effectiveness of self-disclosure transcends culture and language. This study examined the clinical utility of self-disclosure in a culturally and linguistically diverse population: Hebrew-speaking people who stutter in Israel. Method: The experimental protocol replicated Byrd, Croft et al. Participants (N = 92 adults in Israel) viewed a video of either a male or female Hebrew-speaking person who simulated stuttering and self-disclosed informatively, apologetically, or not at all. Participants then rated the speaker on ten traits (i.e. friendly, outgoing, intelligent, confident, engaging, distracting, unfriendly, shy, unintelligent, insecure) using a bipolar likert scale. Result: Results indicated that participants rated the speaker who self-disclosed in a neutral and informative manner as significantly more outgoing compared to the speaker who did not self-disclose at all, supporting the results from Byrd, Croft et al. Additionally, the male speaker was rated as significantly more friendly and outgoing than the female speaker. Conclusion: This study suggests that self-disclosing in a neutral and informative manner can improve listeners’ perceptions of people who stutter similarly across culture and language.
The Impact of COVID-19 on the Adaptive Functioning, Behavioral Problems, and Repetitive Behaviors of Italian Children with Autism Spectrum Disorder: An Observational Study

Children with autism spectrum disorder (ASD) and their families have represented a fragile population on which the extreme circumstances of the COVID-19 outbreak may have doubly impaired. Interruption of therapeutical interventions delivered in-person and routine disruption constituted some of the main challenges they had to face. This study investigated the impact of the COVID-19 lockdown on adaptive functioning, behavioral problems, and repetitive behaviors of children with ASD. In a sample of 85 Italian ASD children (mean age 7 years old; 68 males, 17 females), through a comparison with a baseline evaluation performed during the months preceding COVID-19, we evaluated whether after the compulsory home confinement any improvement or worsening was reported by parents of ASD individuals using standardized instruments (Adaptive Behavior Assessment System (Second Edition), Achenbach Child Behavior Checklist, Repetitive Behavior Scale-Revised). No significant worsening in the adaptive functioning, problematic, and repetitive behaviors emerged after the compulsory home confinement. Within the schooler children, clinical stability was found in reference to both adaptive skills and behavioral aspects, whereas within preschoolers, a significant improvement in adaptive skills emerged and was related to the subsistence of web-delivered intervention, parental work continuance, and online support during the lockdown.
What Is the Best Lens? Comparing the Resolution Power of Genome-Derived Markers and Standard Barcodes

Fungal species delimitation was traditionally carried out with multicopy ribosomal RNA (rRNA) genes, principally for their ease of amplification. Since the efficacy of these markers has been questioned, single-copy protein-encoding genes have been proposed alone or in combination for Multi-Locus Sequence Typing (MLST). In this context, the role of the many sequences obtained with Next-Generation Sequencing (NGS) techniques, in both genomics and metagenomics, further pushes toward an analysis of the efficacy of NGS-derived markers and of the metrics to evaluate the marker efficacy in discriminating fungal species. This paper aims at proposing MeTRe (Mean Taxonomic Resolution), a novel index that could be used both for measuring marker efficacy and for assessing the actual resolution (i.e., the level of separation) between species obtained with different markers or their combinations. In this paper, we described and then employed this index to compare the efficacy of two rRNAs and four single-copy markers obtained from public databases as both an amplicon-based approach and genome-derived sequences. Two different groups of species were used, one with a pathogenic species of Candida that was characterized by relatively well-separated taxa, whereas the other, comprising some relevant species of the sensu stricto group of the genus Saccharomyces, included close species and interspecific hybrids. The results showed the ability of MeTRe to evaluate marker efficacy in general and genome-derived markers specifically.
Establishment of the TALE-code reveals aberrantly activated homeobox gene PBX1 in Hodgkin lymphoma

Homeobox genes encode transcription factors which regulate basic processes in development and cell differentiation and are grouped into classes and subclasses according to sequence similarities. Here, we analyzed the activities of the 20 members strong TALE homeobox gene class in early hematopoiesis and in lymphopoiesis including developing and mature B-cells, T-cells, natural killer (NK)-cells and innate lymphoid cells (ILC). The resultant expression pattern comprised eleven genes and which we termed TALE-code enables discrimination of normal and aberrant activities of TALE homeobox genes in lymphoid malignancies. Subsequent expression analysis of TALE homeobox genes in public datasets of Hodgkin lymphoma (HL) patients revealed overexpression of IRX3, IRX4, MEIS1, MEIS3, PBX1, PBX4 and TGIF1. As paradigm we focused on PBX1 which was deregulated in about 17% HL patients. Normal PBX1 expression was restricted to hematopoietic stem cells and progenitors of T-cells and ILCs but absent in B-cells, reflecting its roles in stemness and early differentiation. HL cell line SUP-HD1 expressed enhanced PBX1 levels and served as an in vitro model to identify upstream regulators and downstream targets in this malignancy. Genomic studies of this cell line therein showed a gain of the PBX1 locus at 1q23 which may underlie its aberrant expression. Comparative expression profiling analyses of HL patients and cell lines followed by knockdown experiments revealed NFIB and TLX2 as target genes activated by PBX1. HOX proteins operate as cofactors of PBX1. Accordingly, our data showed that HOXB9 overexpressed in HL coactivated TLX2 but not NFIB while activating TNFRSF9 without PBX1. Further downstream analyses showed that TLX2 activated TBX15 which operated anti-apoptotically. Taken together, we discovered a lymphoid TALE-code and identified an aberrant network around deregulated TALE homeobox gene PBX1 which may disturb B-cell differentiation in HL by reactivation of progenitor-specific genes. These findings may provide the framework for future studies to exploit possible vulnerabilities of malignant cells in therapeutic scenarios.
Signal Diversity for Laser-Doppler Vibrometers with Raw-Signal Combination

The intensity of the reflected measuring beam is greatly reduced for laser-Doppler vibrometer (LDV) measurements on rough surfaces since a considerable part of the light is scattered and cannot reach the photodetector (laser speckle effect). The low intensity of the reflected laser beam leads to a so-called signal dropout, which manifests as noise peaks in the demodulated velocity signal. In such cases, no light reaches the detector at a specific time and, therefore, no signal can be detected. Consequently, the overall quality of the signal decreases significantly. In the literature, first attempts and a practical implementation to reduce this effect by signal diversity can be found. In this article, a practical implementation with four measuring heads of a Multipoint Vibrometer (MPV) and an evaluation and optimization of an algorithm from the literature is presented. The limitations of the algorithm, which combines velocity signals, are shown by evaluating our measurements. We present a modified algorithm, which generates a combined detector signal from the raw signals of the individual channels, reducing the mean noise level in our measurement by more than 10 dB. By comparing the results of our new algorithm with the algorithms of the state-of-the-art, we can show an improvement of the noise reduction with our approach.
Polymorphisms in Glyoxalase I Gene Are Not Associated with Glyoxalase I Expression in Whole Blood or Markers of Methylglyoxal Stress: The CODAM Study

Glyoxalase 1 (Glo1) is the rate-limiting enzyme in the detoxification of methylglyoxal (MGO) into D-lactate. MGO is a major precursor of advanced glycation endproducts (AGEs), and both are associated with development of age-related diseases. Since genetic variation in GLO1 may alter the expression and/or the activity of Glo1, we examined the association of nine SNPs in GLO1 with Glo1 expression and markers of MGO stress (MGO in fasting plasma and after an oral glucose tolerance test, D-lactate in fasting plasma and urine, and MGO-derived AGEs CEL and MG-H1 in fasting plasma and urine). We used data of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM, n = 546, 60 ± 7 y, 25% type 2 diabetes). Outcomes were compared across genotypes using linear regression, adjusted for age, sex, and glucose metabolism status. We found that SNP4 (rs13199033) was associated with Glo1 expression (AA as reference, standardized beta AT = −0.29, p = 0.02 and TT = −0.39, p = 0.3). Similarly, SNP13 (rs3799703) was associated with Glo1 expression (GG as reference, standardized beta AG = 0.17, p = 0.14 and AA = 0.36, p = 0.005). After correction for multiple testing these associations were not significant. For the other SNPs, we observed no consistent associations over the different genotypes. Thus, polymorphisms of GLO1 were not associated with Glo1 expression or markers of MGO stress, suggesting that these SNPs are not functional, although activity/expression might be altered in other tissues.
Preventive aspect of ayurveda and yoga towards newly emerging disease COVID-19

Abstract The ongoing coronavirus pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) and unique in various facets. The earlier experience from the past severe acute respiratory syndrome (SARS) epidemics seem to be insufficient and there is need for better strategies in public health and medical care. Ayurved & Yog are well known for their preventive and therapeutic aspect, but not getting utilized properly for prevention of Covid 19 crisis which may also be helpful as supportive therapy along with current line of management. This paper is aimed at unrevealing the role of Ayurved and Yoga guidelines established by Department of AYUSH for prevention from SARS-CoV-2 by providing help to improving the quality of supportive/prophylactic therapy in relation with their immunity.
Technological Quality, Amino Acid and Fatty Acid Profile of Broiler Meat Enhanced by Dietary Inclusion of Black Soldier Fly Larvae

We evaluated the effects of full-fat black soldier fly larvae (BSFL) on broiler carcass composition, cut yield, and breast meat quality. Broilers were fed for 42 days with up to 20% dietary inclusion of BSFL (0, 5, 10, 15, and 20%). On day 42, 120 broilers were slaughtered, and images were taken using computed tomography. Breasts, drumsticks, and thighs were collected for cut yield determination. The pH, color, lipid oxidation, cooking loss, shear force, amino acid profile, and fatty acid profile of the breast meat were assessed. There was no dietary effect on carcass composition or meat quality parameters except for fatty and amino acids compositions. When 20% BSFL was included in the diet, individual fatty and amino acids, such as lauric and myristic acids, aspartic acid, glutamine, and lysine, increased by 22.0-, 5.50-, 1.08-, 1.06-, and 1.06-fold, respectively (p < 0.05). Although total polyunsaturated fatty acids decreased, eicosapentaenoic fatty acids (EPA) increased by 78% in the 20% BSFL inclusion group. In conclusion, up to 20%, dietary full-fat BSFL did not affect key meat characteristics but positively increased the levels of the health-claimable omega-3 fatty acid EPA.
ESR1 ChIP-Seq Identifies Distinct Ligand-Free ESR1 Genomic Binding Sites in Human Hepatocytes and Liver Tissue

The estrogen receptor alpha (ESR1) is an important gene transcriptional regulator, known to mediate the effects of estrogen. Canonically, ESR1 is activated by its ligand estrogen. However, the role of unliganded ESR1 in transcriptional regulation has been gaining attention. We have recently shown that ligand-free ESR1 is a key regulator of several cytochrome P450 (CYP) genes in the liver, however ligand-free ESR1 has not been characterized genome-wide in the human liver. To address this, ESR1 ChIP-Seq was conducted in human liver samples and in hepatocytes with or without 17beta-estradiol (E2) treatment. We identified both ligand-dependent and ligand-independent binding sites throughout the genome. These two ESR1 binding categories showed different genomic localization, pathway enrichment, and cofactor colocalization, indicating different ESR1 regulatory function depending on ligand availability. By analyzing existing ESR1 data from additional human cell lines, we uncovered a potential ligand-independent ESR1 activity, namely its co-enrichment with the zinc finger protein 143 (ZNF143). Furthermore, we identified ESR1 binding sites near many gene loci related to drug therapy, including the CYPs. Overall, this study shows distinct ligand-free and ligand-bound ESR1 chromatin binding profiles in the liver and suggests the potential broad influence of ESR1 in drug metabolism and drug therapy.