Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulating Expression of Thioredoxin Interacting Protein (TXNIP) Prevents Secondary Damage and Preserves Visual Function in a Mouse Model of Ischemia/Reperfusion

Retinal neurodegeneration, an early characteristic of several blinding diseases, triggers glial activation, resulting in inflammation, secondary damage and visual impairment. Treatments that aim only at neuroprotection have failed clinically. Here, we examine the impact of modulating thioredoxin interacting protein (TXNIP) to the inflammatory secondary damage and visual impairment in a model of ischemia/reperfusion (IR). Wild type (WT) and TXNIP knockout (TKO) mice underwent IR injury by increasing intraocular pressure for 40 min, followed by reperfusion. An additional group of WT mice received intravitreal TXNIP-antisense oligomers (ASO, 100 µg/2 µL) 2 days post IR injury. Activation of Müller glial cells, apoptosis and expression of inflammasome markers and visual function were assessed. IR injury triggered early TXNIP mRNA expression that persisted for 14 days and was localized within activated Müller cells in WT-IR, compared to sham controls. Exposure of Müller cells to hypoxia-reoxygenation injury triggered endoplasmic reticulum (ER) stress markers and inflammasome activation in WT cells, but not from TKO cells. Secondary damage was evident by the significant increase in the number of occluded acellular capillaries and visual impairment in IR-WT mice but not in IR-TKO. Intervention with TXNIP-ASO prevented ischemia-induced glial activation and neuro-vascular degeneration, and improved visual function compared to untreated WT. Targeting TXNIP expression may offer an effective approach in the prevention of secondary damage associated with retinal neurodegenerative diseases.
Mild-to-Moderate Gestational Iodine Deficiency Processing Disorder

This synopsis paper aims to identify if a common pattern of learning and social difficulties can be conceptualized across recent longitudinal studies investigating the influence of mild-to-moderate gestational iodine deficiency (GID) on offspring’s optimal cognitive and psycho-social development. The main studies investigated are: The Southampton Women’s Study (SWS)—United Kingdom; the Avon Longitudinal Study of Parents and Children (ALSPAC)—United Kingdom; the Gestational Iodine Cohort Longitudinal Study—Tasmania, Australia, and the Danish National Birth Cohort Case-Control Study—Denmark. In contrast to severe GID where there is a global negative impact on neurodevelopment, mild-to-moderate intrauterine iodine deficiency has subtler, but nonetheless important, permanent cognitive and psycho-social consequences on the offspring. This paper links the results from each study and maintains that mild-to-moderate GID is associated with a disorder that is characterized by speed of neural transmitting difficulties that are typically associated with working memory capacity difficulties and attention and response inhibition. The authors maintain that this disorder is better identified as Gestational Iodine Deficiency Processing Disorder (GIDPD), rather than, what to date has often been identified as ‘suboptimal development’. The Autistic Spectrum Disorder (ASD), Attention Deficit, Hyperactivity Disorder (ADHD), language and literacy disorders (learning disabilities and dyslexia) are the main manifestations associated with GIDPD. GIDPD is identified on IQ measures, but selectively and mainly on verbal reasoning IQ subtests, with individuals with GIDPD still operating within the ‘normal’ full-scale IQ range. Greater consideration needs to be given by public health professionals, policy makers and educators about the important and preventable consequences of GID. Specifically, more emphasis should be placed on adequate iodine intake in women prior to pregnancy, as well as during pregnancy and when lactating. Secondly, researchers and others need to further extend, refine and clarify whether GIDPD, as a nosological (medical classification) entity, is a valid disorder and concept for consideration.
TNF-α in Combination with Palmitate Enhances IL-8 Production via The MyD88- Independent TLR4 Signaling Pathway: Potential Relevance to Metabolic Inflammation

Elevated levels of IL-8 (CXCL8) in obesity have been linked with insulin resistance and type 2 diabetes (T2D). The mechanisms that lead to the profound production of IL-8 in obesity remains to be understood. TNF-α and saturated free fatty acids (FFAs) are increased in obese humans and correlate with insulin resistance. Hence, we sought to investigate whether the cooccurrence of TNF-α and FFAs led to increase the production of IL-8 by human monocytes. We found that co-stimulation of human monocytes with palmitate and TNF-α led to increased IL-8 production as compared to those stimulated with palmitate or TNF-α alone. The synergistic production of IL-8 by TNF-α/palmitate was suppressed by neutralizing anti- Toll like receptor 4 (TLR4) antibody and by genetic silencing of TLR4. Both MyD88-deficient and MyD88-competent cells responded comparably to TNF-α/Palmitate. However, TIR-domain-containing adapter-inducing interferon (TRIF) inhibition or interferon regulatory transcription factor 3 (IRF3) knockdown partly blocked the synergistic production of IL-8. Our human data show that increased adipose tissue TNF-α expression correlated positively with IL-8 expression (r = 0.49, P = 0.001). IL-8 and TNF-α correlated positively with macrophage markers including CD68, CD163 and CD86 in adipose tissue. These findings suggest that the signaling cross-talk between saturated fatty acid palmitate and TNF-α may be a key driver in obesity-associated chronic inflammation via an excessive production of IL-8.
Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells

Betula platyphylla bark has been evaluated for the treatment of dermatitis, inflammatory conditions, and cancer. Diarylheptanoids are the major constituents of the B. platyphylla bark and possess various pharmacological effects. Our previous study confirmed the selective antiproliferative effect of platyphylloside (BPP) isolated from B. platyphylla on colon cancer and leukemic cells using 60 different cancer cell lines from thr National Cancer Institution (NCI). In line with previous reports, this study focuses on the apoptotic pathway of BPP, a phenolic glycoside composed of two aromatic rings joined by a seven-carbon chain. Cytotoxicity assays in solid tumor and blood cancer cell models demonstrated that BPP possesses potent antiproliferative activity. The level of apoptosis increased with BPP treatment, causing cell cycle arrest at the G1 phase along with the downregulation of IκBα phosphorylation and BCL-2, as well as upregulation of cleaved caspase 3 and BAX proteins. In addition, BPP displayed potent mitochondrial depolarization effects in Jurkat cells. The combined findings revealed that the cytotoxic effects of BPP were mediated by intracellular signaling, possibly through a mechanism involving the upregulation of mitochondrial reactive oxygen species (ROS). Thus, BPP could be a potential multitarget therapeutic agent in leukemia and colon cancer.
The Relationship between Serum Concentrations of Pro- and Anti-Inflammatory Cytokines and Nutritional Status in Patients with Traumatic Head Injury in the Intensive Care Unit

Background and objective: The aim of the present study was to examine the relationship between serum levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and anti-inflammatory cytokines (IL-10) measured once at the baseline with changes in nutritional status of patients with traumatic head injury (THI) assessed at three consecutive times (24 h after admission, day 6 and day 13) during hospital stay in the intensive care unit (ICU). Materials and Methods: Sixty-four patients with THI were recruited for the current study (over 10 months). The nutritional status of the patients was determined within 24 h after admission and on days 6 and 13, using actual body weight, body composition analysis, and anthropometric measurements. The APACHE II score and SOFA score were also assessed within 24 h of admission and on days 6 and 13 of patients staying in the ICU. Circulatory serum levels of cytokines (IL-6, IL-1β, TNF-α, and IL-10) were assessed once within 24 h of admission. Results: The current study found a significant reduction in BMI, FBM, LBM, MAUAC, and APM, of THI patients with high serum levels the cytokines, over the course of time from the baseline to day 7 and to day 13 in patients staying in the ICU (p < 0.001). It was also found that patients with low levels of some studied cytokines had significant improvement in their nutritional status and clinical outcomes in term of MAUAC, APM, APACHE II score and SOFA score (p < 0.001 to p < 0.01). Conclusion: THI patients who had high serum levels of studied cytokines were more prone to develop a reduction of nutritional status in terms of BMI, FBM, LBM MAUAC and APM over the course of time from patient admission until day 13 of ICU admission.
Effect of terminal arrangement of tryptophan on biological activity of symmetric α‐helix‐forming peptides

It is traditionally believed that the distribution of tryptophan (Trp) residues is critical for the novo design of antimicrobial peptides (AMPs). However, there is scarce knowledge regarding Trp residues arrangement at the head group level. Thus, a set of α‐helical AMPs containing different Trp residue arrangements at the N‐/C‐terminal of sequence were designed to increase the strategy database and analyze their biological activities. The arrangement of the N‐terminal Trp residue significantly improved the bacteriostatic activity of the peptides, but the C‐terminal Trp residue arrangement reduced the biocompatibility of them. WL and LW were effective against Gram‐negative microbes and had high selectivity for bacteria as compared to human erythrocytes and mammalian cells. They both maintained a relatively desirable activity in the presence of physiological salts and serum. It is observed through electron microscope, flow cytometry and fluorescence spectroscopy that target peptides can penetrate bacterial cell membrane and kill it by damaging cell membrane integrity. Collectively, we determined the structure–activity relationship of Trp residue distributions in a symmetric sequence structure and filled the gap in knowledge related to Trp arrangements at the head group level. The obtained results will be helpful in designing of artificial peptide‐based antimicrobials.
Association between Periodontitis and Metabolic Syndrome in a Korean Nationally Representative Sample of Adults Aged 35–79 Years

This study aimed to evaluate the association between periodontitis and metabolic syndrome (MetS) and to investigate risk factors associated with MetS in Korean adults aged 35 to 79 years. Among individuals aged 35–79 years who participated in the Korea National Health and Nutrition Examination Survey 2013–2015, 8314 participants who completed the required examinations and questionnaires were included. Confounding variables related to demographic and socioeconomic status and systemic and oral health-related behaviors were age, gender, household income, education level, smoking, alcohol intake, physical activity, and frequency of daily toothbrushing. Of the 8314 participants, 32.2% were diagnosed with MetS. The prevalence of MetS was 26.6% and 41.6% in those without and with periodontitis, respectively. Among individuals with periodontitis, the prevalence of MetS was 44.3% in males and 36.9% in females. Compared to non-periodontitis, periodontitis was associated with MetS (adjusted OR = 1.422, 95% CI: 1.26–1.61). Age, frequency of daily toothbrushing, and periodontitis were associated with MetS in both males and females. While current smoking and alcohol intake more than twice a week were significantly associated with MetS in males, household income and education level were significantly associated with MetS in females. The findings suggest that periodontitis can be associated with MetS.
Perineuronal Nets and Their Role in Synaptic Homeostasis

Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer’s disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain.
Growth Biocontrol of Foodborne Pathogens and Spoilage Microorganisms of Food by Polish Propolis Extracts

Propolis is a natural mixture produced by bees from plant resin substances. This study focuses on the general characteristics of five samples of Polish extract propolis originating from agricultural areas. Chemical composition with high performance liquid chromatography‒diode array detector method, total content of flavonoids and polyphenols, and antioxidative activity were determined in the ethanol extracts of propolis (EEP) samples. Minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC) and time-kill curves were studied for foodborne pathogens and food spoilage microorganisms. In EEPs the predominant flavonoid compounds were pinocembrin, chrysin, pinobanksin, apigenin, and kaempferol and the predominant phenolic acids were p-coumaric acid, ferulic acid, and caffeic acid. A strong antioxidative action of propolis in vitro was observed (IC50 for DPPH radical was at the level of 0.9–2.1 µg/mL). EEPs had MIC values for bacteria in the range of 1–16 mg/mL, whereas MIC for fungi ranged from 2 to 32 mg/mL. Extract of propolis originating from southern Poland was distinguished by higher content of bioactive components, and stronger antioxidative and antimicrobial activity than EPPs from the remaining areas of Poland. The results indicate the possibility of applying ethanol extracts from Polish propolis to protect food against microbiological spoilage.
Optimized Multi-Position Calibration Method with Nonlinear Scale Factor for Inertial Measurement Units

Navigation grade inertial measurement units (IMUs) should be calibrated after Inertial Navigation Systems (INSs) are assembled and be re-calibrated after certain periods of time. The multi-position calibration methods with advantage of not requiring high-precision equipment are widely discussed. However, the existing multi-position calibration methods for IMU are based on the model of linear scale factors. To improve the precision of INS, the nonlinear scale factors should be calibrated accurately. This paper proposes an optimized multi-position calibration method with nonlinear scale factor for IMU, and the optimal calibration motion of IMU has been designed based on the analysis of sensitivity of the cost function to the calibration parameters. Besides, in order to improve the accuracy and robustness of the optimization, an estimation method on initial values is presented to solve the problem of setting initial values for iterative methods. Simulations and experiments show that the proposed method outperforms the calibration method without nonlinear scale factors. The navigation accuracy of INS can be improved by up to 17% in lab conditions and 12% in the moving vehicle experiment, respectively.
Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41

Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-β) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA–stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells.
Non-Speech Environmental Sound Classification System for Autonomous Surveillance

Sound is one of a human beings most important senses. After vision, it is the sense most used to gather information about the environment. Despite this, comparatively little research has been done into the field of sound recognition. The research that has been done mainly centres around the recognition of speech and music. Our auditory environment is made up of many sounds other than speech and music. This sound information can be taped into for the benefit of specific applications such as security systems. Currently, most researchers are ignoring this sound information. This thesis investigates techniques to recognise environmental non-speech sounds and their direction, with the purpose of using these techniques in an autonomous mobile surveillance robot. It also presents advanced methods to improve the accuracy and efficiency of these techniques. Initially, this report presents an extensive literature survey, looking at the few existing techniques for non-speech environmental sound recognition. This survey also, by necessity, investigates existing techniques used for sound recognition in speech and music. It also examines techniques used for direction detection of sounds. The techniques that have been identified are then comprehensively compared to determine the most appropriate techniques for non-speech sound recognition. A comprehensive comparison is performed using non-speech sounds and several runs are performed to ensure accuracy. These techniques are then ranked based on their effectiveness. The best technique is found to be either Continuous Wavelet Transform feature extraction with Dynamic Time Warping or Mel-Frequency Cepstral Coefficients with Dynamic Time Warping. Both of these techniques achieve a 70% recognition rate. Once the best of the existing classification techniques is identified, the problem of uncountable sounds in the environment can be addressed. Unlike speech recognition, non-speech sound recognition requires recognition from a much wider library of sounds. Due to this near-infinite set of example sounds, the characteristics and complexity of non-speech sound recognition techniques increases. To address this problem, a systematic scheme needs to be developed for non-speech sound classification. Several different approaches are examined. Included is a new design for an environmental sound taxonomy based on an environmental sound alphabet. This taxonomy works over three levels and classifies sounds based on their physical characteristics. Its performance is compared with a technique that generates a structured tree automatically. These structured techniques are compared for different data sets and results are analysed. Comparable results are achieved for these techniques with the same data set as previously used. In addition, the results and greater information from these experiments is used to infer some information about the structure of environmental sounds in general. Finally, conclusions are drawn on both sets of techniques and areas of future research stemming from this thesis are explored.
Effectiveness and safety of osimertinib in patients with metastatic EGFR T790M-positive NSCLC: An observational real-world study

Osimertinib showed encouraging efficacy in patients with advanced EGFR T790M-positive NSCLC in previous randomized controlled trials. This real-world study aimed to evaluate the effectiveness and safety of osimertinib in a real-world setting. This observational study (NCT03133234) included 74 patients with metastatic EGFR T790M-positive NSCLC who progressed on prior EGFR TKI therapy and received osimertinib between May 2016 and April 2018 at the Kiang Wu Hospital in Macau. Response rate (RR) and other endpoints (progression-free survival [PFS], overall survival [OS], disease control rate [DCR], stable disease rate, and adverse events) were assessed. Survival data were estimated using the Kaplan-Meier method. All patients had stage IV lung adenocarcinoma and 25.6% had brain metastases; median age was 58 years (range 28–84 years) and 83.8% of patients had received at least three prior lines of treatment. The median duration of osimertinib treatment was 8 months (range, 1–25 months). RR and DCR were 67.5% (95% CI 56.9–78.1) and 79.8% (95% CI 70.7–88.9), respectively, while 12.1% had stable disease. The median PFS was 9.0 months (95% CI 6.7–11.2 months), and the median OS was 12.0 months (95% CI 8.8–15.1 months). Nausea (25.8%) and decreased appetite (20.2%) were the most common adverse events associated with osimertinib treatment. Even though most patients had at least three lines of prior treatment, real-world RR and PFS with osimertinib in this study were consistent with those from randomized controlled trials; no new safety signals were observed.