Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Combination of COX-2 Inhibitor and Antioxidant Therapy for Modulating Oxidative Stress Associated with Intestinal Ischemic Reperfusion Injury and Endotoxemia

Background: Intestinal ischemic reperfusion (I/R) injury is associated with a high mortality rate; this condition is also related to significant endotoxemia and systemic inflammation. The preservation of tissue perfusion and a sufficient blood flow are required to deliver nutrients and oxygen, preserve metabolic pathways, and eliminate waste products. Oxidative stress plays a fundamental role in intestinal I/R injury and leads to disruption of the mucosal barrier and necrosis, allowing the migration of endotoxins and luminal bacteria into the systemic circulation. In this study, we evaluated the beneficial effects of a cyclooxygenase (COX)-2 inhibitor—firocoxib—plus the antioxidant vitamin C in a rat model of intestinal I/R injury. Methods: We used a rat model of I/R injury in which the superior mesenteric artery was clamped for 30 min by a vascular clamp, and the animals were then allowed 1 h of reperfusion. Results: Our results show the importance of combined anti-inflammatory and antioxidant treatment for the prevention of intestinal I/R injury that leads to reduced systemic endotoxemia. We observed a significantly synergistic effect of firocoxib and vitamin C in reducing intestinal wall damage and oxidative stress, leading to a significant reduction of inflammation and endotoxemia. Conclusions: Our results indicate that this approach could be a new pharmacological protocol for intestinal colic or ischemic injury-induced endotoxemia.
The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.
Breaking the Percent Memory Retention Ceiling using Bayesian Statistics

Abstract Objectives: Neuropsychological tests of episodic memory often include a measure of memory retention to facilitate the diagnosis of memory disorders. However, the traditional percent retention (PR) score has limited interpretability when smaller amounts of information are both initially learned and later recalled, creating a pseudo-ceiling effect. To improve psychometrics of PR, we investigated a scoring procedure that incorporates levels of certainty into estimates of memory retention based on learning level. Methods: Word-list recall data from adults with traumatic brain injury were modeled using a uniform prior in the Bayesian framework. From the resultant posterior probability distributions, we derived a measure referred to as retention probability (RPr), which distinguishes the retention of relatively good and poor learners. PR and RPr scores were compared on their distributional properties and associations with theoretically related memory measures. Results: Significant distributional differences between PR and RPr were observed. RPr removed the conspicuous ceiling of PR, resulting in stronger correlational and predictive relationships with other memory measures. Conclusion: A Bayesian procedure for quantifying memory retention has psychometric advantages and potentially widespread applicability for measuring the change in behavioral features over time. Future directions are briefly discussed. A sample RPr calculator is provided for interactive exploration of the method.
Electron Microscopic Studies on Localization of Lead in Organs of Typha angustifolia Grown on Contaminated Soil

A greenhouse study was conducted to observe the localization of lead in narrow-leaved cattail, Typha angustifolia. Light and transmission electron microscopic studies were performed on root, rhizome and leaf of the cattail grown in control (75 kg dry weight of soil with no added lead) and in the same weight of soil amended with 20,000 mg lead nitrate. At 15 and 90 days after planting, most lead was accumulated in root cells around vacuoles and slowly transported to leaves. In the lead-contaminated soil, parts of the root cell wall were damaged at the end of the experiment. Lead was deposited in the rhizome near the cell wall. Similar deposits were observed in the roots and rhizomes suggesting that lead was transported and localized in a similar area, whereas the leaf cells accumulated lead in the chloroplasts.
Cost-effectiveness of programmed cell death ligand 1 testing and tumor mutational burden testing of immune checkpoint inhibitors for advanced non-small cell lung cancer

To the Editor: Worldwide, lung cancer, particularly nonsmall cell lung cancer (NSCLC), is the leading cause of tumor-related death. Cost-effectiveness analysis show no economic benefits for advanced NSCLC patients over chemotherapy. Furthermore, tests such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) tests, evaluated via immunohistochemical methods and next-generation sequencing, respectively, are widely used for screening potential beneficiaries of immune checkpoint inhibitors (ICIs). However, these two methods have different predictive values, making their comprehensive evaluation the focus of the current controversy.
Intravenous peramivir vs oral oseltamivir in high‐risk emergency department patients with influenza: Results from a pilot randomized controlled study

Peramivir offers a single‐dose intravenous (IV) treatment option for influenza (vs 5‐day oral dosing for oseltamivir). We sought to compare outcomes of emergency department (ED) patients at high risk for influenza complications treated with IV peramivir vs oral oseltamivir.
c-di-AMP Accumulation Impairs Muropeptide Synthesis in Listeria monocytogenes

The bacterial second messenger c-di-AMP is produced by a large number of bacteria and conditionally essential to many species. Conversely, c-di-AMP accumulation is also toxic to bacterial physiology and pathogenesis, but its mechanisms are largely undefined. We found that in Listeria monocytogenes, elevated c-di-AMP levels diminished muropeptide synthesis and increased susceptibility to cell wall-targeting antimicrobials. Cell wall defects might be an important mechanism for attenuated virulence in bacteria with high c-di-AMP levels. ABSTRACT Cyclic di-AMP (c-di-AMP) is an essential and ubiquitous second messenger among bacteria. c-di-AMP regulates many cellular pathways through direct binding to several molecular targets in bacterial cells. c-di-AMP depletion is well known to destabilize the bacterial cell wall, resulting in increased bacteriolysis and enhanced susceptibility to cell wall targeting antibiotics. Using the human pathogen Listeria monocytogenes as a model, we found that c-di-AMP accumulation also impaired cell envelope integrity. An L. monocytogenes mutant deleted for c-di-AMP phosphodiesterases (pdeA pgpH mutant) exhibited a 4-fold increase in c-di-AMP levels and several cell wall defects. For instance, the pdeA pgpH mutant was defective for the synthesis of peptidoglycan muropeptides and was susceptible to cell wall-targeting antimicrobials. Among different muropeptide precursors, we found that the pdeA pgpH strain was particularly impaired in the synthesis of d-Ala–d-Ala, which is required to complete the pentapeptide stem associated with UDP–N-acetylmuramic acid (MurNAc). This was consistent with an increased sensitivity to d-cycloserine, which inhibits the d-alanine branch of peptidoglycan synthesis. Finally, upon examining d-Ala:d-Ala ligase (Ddl), which catalyzes the conversion of d-Ala to d-Ala–d-Ala, we found that its activity was activated by K+. Based on previous reports that c-di-AMP inhibits K+ uptake, we propose that c-di-AMP accumulation impairs peptidoglycan synthesis, partially through the deprivation of cytoplasmic K+ levels, which are required for cell wall-synthetic enzymes. IMPORTANCE The bacterial second messenger c-di-AMP is produced by a large number of bacteria and conditionally essential to many species. Conversely, c-di-AMP accumulation is also toxic to bacterial physiology and pathogenesis, but its mechanisms are largely undefined. We found that in Listeria monocytogenes, elevated c-di-AMP levels diminished muropeptide synthesis and increased susceptibility to cell wall-targeting antimicrobials. Cell wall defects might be an important mechanism for attenuated virulence in bacteria with high c-di-AMP levels.
Pharmacological strategies to treat attacks of episodic migraine in adults

ABSTRACT Introduction Migraine patients prioritize early complete relief of headache and associated symptoms, sustained freedom of pain, and good tolerability. One major obstacle for the successful use of drug treatment of migraine attack is that the speed of action of triptans, 5-HT1B/1D receptor agonists, is delayed. Areas covered In this review, the author discusses the following features of acute migraine drugs: pharmacology; pharmacokinetics, and absorption of drugs during migraine attacks. Next, dose–response curves for effect; and the delayed onset of action is reviewed. In the more clinical part of the review, the following items are discussed: overall clinical judgments; comparison of triptans; comparison of triptans with NSAIDs; early intervention with triptans; medication-overuse headache; comments on the effect of gepants; and the general principle of acute migraine therapy. Expert opinion The delay in the onset of effect of acute migraine drugs is likely due to a complex antimigraine system involving more than one site of action. Investigations into the mechanisms of the delay should have a high priority, both in studies with animals, migraine models, and in migraine patients during attacks. Non-oral administration of antimigraine drugs resulting in early absorption of drugs should be developed as they possibly also can increase Emax.
Algorithm to quantify nuclear features and confidence intervals for classification of oral neoplasia from high-resolution optical images

Abstract. Purpose: In vivo optical imaging technologies like high-resolution microendoscopy (HRME) can image nuclei of the oral epithelium. In principle, automated algorithms can then calculate nuclear features to distinguish neoplastic from benign tissue. However, images frequently contain regions without visible nuclei, due to biological and technical factors, decreasing the data available to and accuracy of image analysis algorithms. Approach: We developed the nuclear density-confidence interval (ND-CI) algorithm to determine if an HRME image contains sufficient nuclei for classification, or if a better image is required. The algorithm uses a convolutional neural network to exclude image regions without visible nuclei. Then the remaining regions are used to estimate a confidence interval (CI) for the number of abnormal nuclei per mm2, a feature used by a previously developed algorithm (called the ND algorithm), to classify images as benign or neoplastic. The range of the CI determines whether the ND-CI algorithm can classify an image with confidence, and if so, the predicted category. The ND and ND-CI algorithm were compared by calculating their positive predictive value (PPV) and negative predictive value (NPV) on 82 oral biopsies with histopathologically confirmed diagnoses. Results: After excluding the images that could not be classified with confidence, the ND-CI algorithm had higher PPV (65% versus 59%) and NPV (78% versus 75%) than the ND algorithm. Conclusions: The ND-CI algorithm could improve the real-time classification of HRME images of the oral epithelium by informing the user if an improved image is required for diagnosis.
The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study.

BACKGROUND Current drug treatments have little efficacy in advanced-to-end-stage Parkinson's disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit. OBJECTIVE To determine the feasibility and safety of the selective D1/D5 dopamine partial agonist PF 06412562 in advPD. METHODS A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25 + 20 mg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. RESULTS Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n = 1, SoC: n = 0), moderate (PF-06412562: n = 1, SoC: n = 1), or severe but non-serious (PF-06412562: n = 3, SoC: n = 2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians' and four participants per caregivers' rating. CONCLUSION PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs.
The role of cochlear place coding in the perception of frequency modulation

Natural sounds convey information via frequency and amplitude modulations (FM and AM). Humans are acutely sensitive to the slow rates of FM that are crucial for speech and music. This sensitivity has long been thought to rely on precise stimulus-driven auditory-nerve spike timing (time code), whereas a coarser code, based on variations in the cochlear place of stimulation (place code), represents faster FM rates. We tested this theory in listeners with normal and impaired hearing, spanning a wide range of place-coding fidelity. Contrary to predictions, sensitivity to both slow and fast FM correlated with place-coding fidelity. We also used incoherent AM on two carriers to simulate place coding of FM and observed poorer sensitivity at high carrier frequencies and fast rates, two properties of FM detection previously ascribed to the limits of time coding. The results suggest a unitary place-based neural code for FM across all rates and carrier frequencies.
Driving Performance and Technology Acceptance Evaluation in Real Traffic of a Smartphone-Based Driver Assistance System

Technological advances are changing every aspect of our lives, from the way we work, to how we learn and communicate. Advanced driver assistance systems (ADAS) have seen an increased interest due to the potential of ensuring a safer environment for all road users. This study investigates the use of a smartphone-based ADAS in terms of driving performance and driver acceptance, with the aim of improving road safety. The mobile application uses both cameras of a smartphone to monitor the traffic scene and the driver’s head orientation, and offers an intuitive user interface that can display information in a standard mode or in augmented reality (AR). A real traffic experiment consisting of two driving conditions (a baseline scenario and an ADAS scenario), was conducted in Brasov, Romania. Objective and subjective data were recorded from twenty-four participants with a valid driver’s license. Results showed that the use of the ADAS influences the driving performance, as most of them adopted an increased time headway and lower mean speeds. The technology acceptance model (TAM) questionnaire was used to assess the users’ acceptance of the proposed driver assistance system. The results showed significant interrelations between acceptance factors, while the hierarchical regression analysis indicates that the variance of behavioral intention (BI) can be predicted by attitude toward behavior.
COVID-19 Infection: Concise Review Based on the Immunological Perspective

ABSTRACT The outbreak of coronavirus disease 2019 (COVID-19) has posed a serious threat to public health. There is an urgent need for discovery methods for the prevention and treatment of COVID-19 infection. Understanding immunogenicity together with immune responses are expected to provide further information about this virus. We hope that this narrative review article may create new insights for researchers to take great strides toward designing vaccines and novel therapies in the near future. The functional properties of the immune system in COVID-19 infection is not exactly clarified yet. This is compounded by the many gaps in our understanding of the SARS-CoV-2 immunogenicity properties. Possible immune responses according to current literature are discussed as the first line of defense and acquired immunity. Here, we focus on proposed modern preventive immunotherapy methods in COVID-19 infection.
Biased Mutation and Selection in RNA Viruses

Abstract RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In −ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.
Comparative Pathology of the Peripheral Nervous System

The peripheral nervous system (PNS) relays messages between the central nervous system (brain and spinal cord) and the body. Despite this critical role and widespread distribution, the PNS is often overlooked when investigating disease in diagnostic and experimental pathology. This review highlights key features of neuroanatomy and physiology of the somatic and autonomic PNS, and appropriate PNS sampling and processing techniques. The review considers major classes of PNS lesions including neuronopathy, axonopathy, and myelinopathy, and major categories of PNS disease including toxic, metabolic, and paraneoplastic neuropathies; infectious and inflammatory diseases; and neoplasms. This review describes a broad range of common PNS lesions and their diagnostic criteria and provides many useful references for pathologists who perform PNS evaluations as a regular or occasional task in their comparative pathology practice.
Coupling of Anodic Oxidation and Soil Remediation Processes: A Review

In recent years, due to industrial modernization and agricultural mechanization, several environmental consequences have been observed, which make sustainable development difficult. Soil, as an important component of ecosystem and a key resource for the survival of human and animals, has been under constant contamination from different human activities. Contaminated soils and sites require remediation not only because of the hazardous threat it possess to the environment but also due to the shortage of fresh land for both agriculture and urbanization. Combined or coupled remediation technologies are one of the efficient processes for the treatment of contaminated soils. In these technologies, two or more soil remediation techniques are applied simultaneously or sequentially, in which one technique complements the other, making the treatment very efficient. Coupling anodic oxidation (AO) and soil remediation for the treatment of soil contaminated with organics has been studied via two configurations: (i) soil remediation, ex situ AO, where AO is used as a post-treatment stage for the treatment of effluents from soil remediation process and (ii) soil remediation, in situ AO, where both processes are applied simultaneously. The former is the most widely investigated configuration of the combined processes, while the latter is less common due to the greater diffusion dependency of AO as an electrode process. In this review, the concept of soil washing (SW)/soil flushing (SF) and electrokinetic as soil remediation techniques are briefly explained followed by a discussion of different configurations of combined AO and soil remediation.
Stability profile of flavour-active ester compounds in ale and lager beer during storage

Currently, one of the main quality problems of beer is the change of its chemical composition during storage, which alters its sensory properties. In this study, ale and lager beers were produced and aged for three months at two storage temperatures. Concentration of volatile ester compounds (VECs) in the beers was regularly monitored by gas chromatographic analysis of the headspace samples to establish changes in ester flavour profile with time. Generally, VECs were more stable during storage at 4°C, compared to room temperature for both ale and lager beer produced. Of the VECs produced, ethyloctanoate was the least stable in ale beer, with 32.47% decrease in concentration observed at room temperature, while phenyl ethyl acetate was the most stable compound decreasing by only 9.82% after three months. In lager beer, VECs were relatively stable decreasing by only 7.93% after three months, while ethyl decanoate was the least stable, with 36.77% decrease in concentration observed at room temperature. Results obtained in this study can be helpful in developing appropriate technological process to control the stability of these important flavour esters in beer. Keywords : Esters, stability, storage temperature, storage duration African Journal of Biotechnology Vol. 12(5), pp. 491-498