Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting MET in Non-Small Cell Lung Cancer (NSCLC): A New Old Story?

In recent years, we have seen the development and approval for clinical use of an increasing number of therapeutic agents against actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC). Among them, selective inhibitors, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting the mesenchymal–epithelial transition (MET) receptor, have been studied in patients with advanced NSCLC with MET deregulation, primarily due to exon 14 skipping mutations or MET amplification. Some MET TKIs, including capmatinib and tepotinib, have proven to be highly effective in this molecularly defined subgroup of patients and are already approved for clinical use. Other similar agents are being tested in early-stage clinical trials with promising antitumor activity. The purpose of this review is to provide an overview of MET signaling pathways, MET oncogenic alterations primarily focusing on exon 14 skipping mutations, and the laboratory techniques used to detect MET alterations. Furthermore, we will summarize the currently available clinical data and ongoing studies on MET inhibitors, as well as the mechanisms of resistance to MET TKIs and new potential strategies, including combinatorial approaches, to improve the clinical outcomes of MET exon 14-altered NSCLC patients.
Hexavalent Chromium Disrupts Oocyte Development in Rats by Elevating Oxidative Stress, DNA Double-Strand Breaks, Microtubule Disruption, and Aberrant Segregation of Chromosomes

Environmental and occupational exposure to hexavalent chromium, Cr(VI), causes female reproductive failures and infertility. Cr(VI) is used in more than 50 industries and is a group A carcinogen, mutagenic and teratogenic, and a male and female reproductive toxicant. Our previous findings indicate that Cr(VI) causes follicular atresia, trophoblast cell apoptosis, and mitochondrial dysfunction in metaphase II (MII) oocytes. However, the integrated molecular mechanism of Cr(VI)-induced oocyte defects is not understood. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to oocyte incompetence in superovulated rats. Postnatal day (PND) 22 rats were treated with potassium dichromate (1 and 5 ppm) in drinking water from PND 22–29 and superovulated. MII oocytes were analyzed by immunofluorescence, and images were captured by confocal microscopy and quantified by Image-Pro Plus software, Version 10.0. 5. Our data showed that Cr(VI) increased microtubule misalignment (~9 fold), led to missegregation of chromosomes and bulged and folded actin caps, increased oxidative DNA (~3 fold) and protein (~9–12 fold) damage, and increased DNA double-strand breaks (~5–10 fold) and DNA repair protein RAD51 (~3–6 fold). Cr(VI) also induced incomplete cytokinesis and delayed polar body extrusion. Our study indicates that exposure to environmentally relevant doses of Cr(VI) caused severe DNA damage, distorted oocyte cytoskeletal proteins, and caused oxidative DNA and protein damage, resulting in developmental arrest in MII oocytes.
Intravascular Ultrasound Guided Intervention in Calcified Coronary Lesions Showed Good Clinical Outcomes during One Year Follow-Up

Background: Calcified coronary lesions can cause stent under-expansion, malapposition, and polymer degradation, hence increasing the risk of adverse clinical outcomes. Percutaneous coronary intervention (PCI) guided by intravascular ultrasound (IVUS) has been used regularly to improve outcomes. Our primary aim was to evaluate the clinical efficacy of IVUS-guided PCI in calcified coronary lesions. Methods: From August 2018 to December 2021, we prospectively included 300 patients in the CAPIRO study (CAlcified plaque in patients receiving Resolute Onyx®) at three educational hospitals in Jeonbuk Province. We studied 243 patients (265 lesions) who were followed up for over a year. Based on coronary calcification by IVUS analysis, the patient population was categorized into two groups (Group I: non/mild calcification; Group II: moderate/severe calcification (maximum calcium arc >180° and calcium length > 5 mm)). One-to-one Propensity Score Matching was used to match the baseline characteristics. The stent expansion rate was analyzed by recent criteria. The primary clinical outcome was Major Adverse Cardiac Events (MACE), which included Cardiac death, Myocardial Infarction (MI), and Target Lesion Revascularization (TLR). Results: After follow-up time, the MACE rate in Group I was 1.99%, comparable to Group II’s 1.09% (p = 0.594). The components of MACE did not significantly differ between the two groups. Based on absolute MSA or MSA/MVA at MSA site criteria, the stent expansion rate in Group II was lower than that of Group I. Nevertheless, based on recent relative criteria, the stent expansion rate in both groups was comparable. Conclusions: After more than a year of follow-up, IVUS-guided PCI in moderate/severe calcification lesions was associated with good clinical outcomes, which was comparable with non/mild calcification lesions. Future studies with a larger sample size and a more extended follow-up period are required to clarify our findings.
The Behavioral Intention to Adopt Circular Economy-Based Digital Technology for Agricultural Waste Valorization

Thailand generates considerable amounts of agricultural food waste. This research focuses on the manufacturing and retail agricultural food system in the northeastern region of Thailand. Our study aimed to investigate the user segments and factors that influence users’ behavioral intentions to utilize mobile technology for agricultural waste valorization. This study is based on the Unified Theory of the Adoption and Utilization of Technology (UTAUT2). In order to classify these segments, we performed a cluster analysis using demographic variables: gender, age, and income. In addition, the researchers employed a method known as multigroup structural equation modeling to determine and contrast the users’ behavioral intentions. The results showed two types of users: (1) older users with various income ranges, and (2) younger users with a low-income range. Explicitly, age and income were the significant variables for the demographic segmentation, but gender was not. The results also revealed that social influence, price value, and trust highly affected the behavioral intentions of older and various-income users, but did not influence younger and low-income users. However, privacy strongly affected the behavioral intentions in the younger segment, but not those in the older one. Lastly, habit or regularity influenced the behavioral intentions of users in both segments. This study highlights implications for how developers and practitioners might adapt their platform strategies using a circular agricultural platform and user behaviors.
Prevalence, Intensity and Psychosocial Burden of Acne Itch: Two Different Cohorts Study

Background: Chronic itch is a common symptom of inflammatory skin diseases. This study was undertaken to evaluate the presence and intensity of itching in two different cohorts of acne subjects. Additionally, the influence of itching on the psychosocial status of acne individuals was assessed. Methods: Consecutive acne patients seeking dermatological advice and university students diagnosed with acne during dermatological screening were considered. The clinical and psychological aspects of acne were assessed using a variety of instruments. Results: About 40% of acne subjects in both cohorts reported itching. The mean WI-NRS during the last 3 days in acne patients was 3.83 ± 2.31 points (mild itch) and was significantly more severe (p < 0.001) than in university students diagnosed with acne (2.09 ± 1.29 points). Itch intensity did not depend on the clinical severity of acne. In consecutive acne patients, itch intensity correlated with quality-of-life impairments (assessed using DLQI and CADI) and HADS scores. There was no correlation between itch intensity and stigmatization levels. Conclusions: Itching seems to be a common phenomenon in acne sufferers. Acne itch significantly influences patients’ well-being and should be considered in a holistic approach to acne patients.
Cold Physical Plasma-Mediated Fenretinide Prodrug Activation Confers Additive Cytotoxicity in Epithelial Cells

Cold physical plasma is a partially ionized gas operated at body temperature and utilized for heat-sensitive technical and medical purposes. Physical plasma is a multi-component system consisting of, e.g., reactive species, ions and electrons, electric fields, and UV light. Therefore, cold plasma technology is an interesting tool for introducing biomolecule oxidative modifications. This concept can be extended to anticancer drugs, including prodrugs, which could be activated in situ to enhance local anticancer effects. To this end, we performed a proof-of-concept study on the oxidative prodrug activation of a tailor-made boronic pinacol ester fenretinide treated with the atmospheric pressure argon plasma jet kINPen operated with either argon, argon–hydrogen, or argon–oxygen feed gas. Fenretinide release from the prodrug was triggered via Baeyer–Villiger-type oxidation of the boron–carbon bond based on hydrogen peroxide and peroxynitrite, which were generated by plasma processes and chemical addition using mass spectrometry. Fenretinide activation led to additive cytotoxic effects in three epithelial cell lines in vitro compared to the effects of cold plasma treatment alone regarding metabolic activity reduction and an increase in terminal cell death, suggesting that cold physical plasma-mediated prodrug activation is a new direction for combination cancer treatment studies.
Design and Development of a Non-Contact ECG-Based Human Emotion Recognition System Using SVM and RF Classifiers

Emotion recognition becomes an important aspect in the development of human-machine interaction (HMI) systems. Positive emotions impact our lives positively, whereas negative emotions may cause a reduction in productivity. Emotionally intelligent systems such as chatbots and artificially intelligent assistant modules help make our daily life routines effortless. Moreover, a system which is capable of assessing the human emotional state would be very helpful to assess the mental state of a person. Hence, preventive care could be offered before it becomes a mental illness or slides into a state of depression. Researchers have always been curious to find out if a machine could assess human emotions precisely. In this work, a unimodal emotion classifier system in which one of the physiological signals, an electrocardiogram (ECG) signal, has been used is proposed to classify human emotions. The ECG signal was acquired using a capacitive sensor-based non-contact ECG belt system. The machine-learning-based classifiers developed in this work are SVM and random forest with 10-fold cross-validation on three different sets of ECG data acquired for 45 subjects (15 subjects in each age group). The minimum classification accuracies achieved with SVM and RF emotion classifier models are 86.6% and 98.2%, respectively.
Increased Survival Concomitant with Unchanged Morbidity and Cognitive Disability among Infants Born at the Limit of Viability before 24 Gestational Weeks in 2009–2019

Introduction: The aim was to determine risk factors among mothers and outcomes for their children born at the limit of viability in 2009–2019, before and after the introduction of extended interventionist guidelines. Methods: A retrospective cohort study of births at 22 + 0–23 + 6 gestational weeks in a Swedish Region in 2009–2015 (n = 119), as compared to 2016–2019 (n = 86) after the introduction of new national interventionist guidelines. Infant mortality, morbidity, and cognitive functions at 2 years corrected age according to the Bayley-III Screening Test were monitored. Results: Maternal risk factors for extreme preterm birth were identified. The intrauterine fetal death rates were comparable. Among births at 22 weeks, the neonatal mortality tended to decrease (96 vs. 76% of live births (p = 0.05)), and the 2-year survival tended to increase (4 vs. 24% (p = 0.05)). Among births at 23 weeks, the neonatal mortality decreased (56 vs. 27% of live births (p = 0.01)), and the 2-year survival increased (42 vs. 64% (p = 0.03)). Somatic morbidity and cognitive disability at 2 years corrected age were unchanged. Conclusion: We identified maternal risk factors that emphasize the need for standardized follow-up and counseling for women at increased risk of preterm birth at the limit of viability. The increased infant survival concomitant with unchanged morbidity and cognitive disability highlight the importance of ethical considerations regarding interventionist approaches at threatening preterm birth before 24 weeks.
Each Cellular Compartment Has a Characteristic Protein Reactive Cysteine Ratio Determining Its Sensitivity to Oxidation

Signaling and detoxification of Reactive Oxygen Species (ROS) are important patho-physiologcal processes. Despite this, we lack comprehensive information on individual cells and cellular structures and functions affected by ROS, which is essential to build quantitative models of the effects of ROS. The thiol groups from cysteines (Cys) in proteins play a major role in redox defense, signaling, and protein function. In this study, we show that the proteins in each subcellular compartment contain a characteristic Cys amount. Using a fluorescent assay for -SH in thiolate form and amino groups in proteins, we show that the thiolate content correlates with ROS sensitivity and signaling properties of each compartment. The highest absolute thiolate concentration was found in the nucleolus, followed by the nucleoplasm and cytoplasm whereas protein thiolate groups per protein showed an inverse pattern. In the nucleoplasm, protein reactive thiols concentrated in SC35 speckles, SMN, and the IBODY that accumulated oxidized RNA. Our findings have important functional consequences, and explain differential sensitivity to ROS.
Generation and Characterization of a Zebrafish Model for ADGRV1-Associated Retinal Dysfunction Using CRISPR/Cas9 Genome Editing Technology

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the ADGRV1 gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying ADGRV1-associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner. Zebrafish have been recognized as a suitable model to study Usher syndrome-associated retinal dysfunction. Using CRISPR/Cas9 technology we introduced a 4bp deletion in adgrv1 exon 9 (adgrv1rmc22). Immunohistochemical analysis showed that Adgrv1 was absent from the region of the photoreceptor connecting cilium in the adgrv1rmc22 zebrafish retina. Here, the absence of Adgrv1 also resulted in reduced levels of the USH2 complex members usherin and Whrnb, suggesting that Adgrv1 interacts with usherin and Whrnb in zebrafish photoreceptors. When comparing adgrv1rmc22 zebrafish with wild-type controls, we furthermore observed increased levels of aberrantly localized rhodopsin in the photoreceptor cell body, and decreased electroretinogram (ERG) B-wave amplitudes which indicate that the absence of Adgrv1 results in impaired retinal function. Based on these findings we present the adgrv1rmc22 zebrafish as the first ADGRV1 mutant model that displays an early retinal dysfunction. Moreover, the observed phenotypic changes can be used as quantifiable outcome measures when evaluating the efficacy of future novel therapeutic strategies for ADGRV1-associated RP.
A Genotyping Method for Detecting Foreign Buffalo Material in Mozzarella di Bufala Campana Cheese Using Allele-Specific- and Single-Tube Heminested-Polymerase Chain Reaction

Mozzarella di Bufala Campana (MdBC) cheese is a Protected Designation of Origin (PDO) product that is important for the economy and cultural heritage of the Campania region. Food fraud can undermine consumers’ trust in this dairy product and harm the livelihood of local producers. The current methods for detecting adulteration in MdBC cheese due to the use of buffalo material from foreign countries could exhibit limitations associated with the required use of expensive equipment, time-consuming procedures, and specialized personnel. To address these limits here, we propose a rapid, reliable, and cost-effective genotyping method that can detect foreign buffalo milk in a counterpart from the PDO area and in MdBC cheese, ensuring the quality and authenticity of the latter dairy product. This method is based on dedicated allele-specific and single-tube heminested polymerase chain reaction procedures. By using allele-specific primers that are designed to detect the nucleotide g.472G>C mutation of the CSN1S1Bbt allele, we distinguished an amplicon of 330 bp in the amplification product of DNA when extracted from milk and cheese, which is specific to the material originating from foreign countries. By spiking foreign milk samples with known amounts of the counterpart from the PDO area, the sensitivity of this assay was determined to be 0.01% v/v foreign to PDO milk. Based on a rough estimate of its simplicity, reliability, and cost, this method could be a valuable tool for identifying adulterated buffalo PDO dairy products.
VAX014, an Oncolytic Therapy, Reduces Adenomas and Modifies Colon Microenvironment in Mouse Model of CRC

Colorectal cancer (CRC) remains the third most common form of cancer and, despite its reduced mortality, results in over 50,000 deaths annually, highlighting the need for novel therapeutic approaches. VAX014 is a novel clinical-stage, oncolytic bacterial minicell-based therapy shown to elicit protective antitumor immune responses in cancer, but it has not been fully evaluated in CRC. Here, VAX014 was demonstrated to induce oncolysis in CRC cell lines in vitro and was evaluated in vivo, both as a prophylactic (before spontaneous development of adenomatous polyps) and as a neoadjuvant treatment using the Fabp-CreXApcfl468 preclinical animal model of colon cancer. As a prophylactic, VAX014 significantly reduced the size and number of adenomas without inducing long term changes in the gene expression of inflammatory, T helper 1 antitumor, and immunosuppression markers. In the presence of adenomas, a neoadjuvant VAX014 treatment reduced the number of tumors, induced the gene expression of antitumor TH1 immune markers in adenomas, and promoted the expansion of the probiotic bacterium Akkermansia muciniphila. The neoadjuvant VAX014 treatment was associated with decreased Ki67 proliferation in vivo, suggesting that VAX014 inhibits adenoma development through both oncolytic and immunotherapeutic effects. Combined, these data support the potential of VAX014 treatment in CRC and “at risk” polyp-bearing or early adenocarcinoma populations.
Suicidal and aggressive behavior among populations within institutional quarantine and isolation centers of COVID-19 in eastern Ethiopia: A cross-sectional study

Introduction The coronavirus disease is still not under the control globally and has caused various mental health problems such as depression, anxiety, suicide, and aggressive behavior in different populations. The pandemic-related issues which are applied to control the pandemic such as protection measures against COVID-19, social distancing, isolation, and quarantine can also trigger mental health problems. Objective This study aimed to assess suicidal behavior and aggression, and its correlates during COVID-19 among populations within institutional quarantine and isolation centers in Ethiopia. Method A cross-sectional study was conducted among a sample of 392 participants. The convenience sampling method was used to select the study participants. Suicide Behavioral Questionnaire-Revised (SBQ-R) and the Modified Overt Aggression Scale (MOAS)were applied to determine the suicide and aggressive behavior of study participants respectively. Epi-data 3.1 and SPSS 20.0were used to enter and analyze the data respectively. Logistic and linear regressions were fitted to explore correlates associated with suicidal behavior and aggression respectively. Results The prevalence of suicidal behavior was 8.7% (95% CI: 6.1, 11.5) whereas the mean total score of behavioral aggression was 2.45±5.90 (95% CI: 1.84, 3.08). Being female (AOR = 2.63, 95% CI: 1.09, 6.32), having common mental disorders (AOR = 6.08, 95% CI: 2.32, 15.93), manifesting the symptoms of COVID-19 (AOR = 2.17, 95% CI: 1.48, 2.86), and poor social support (AOR = 7.30, 95% CI: 1.44, 37.10) were significantly associated with suicidal behavior, whereas male gender (β coefficient = 3.0, 95% CI: 1.35, 4.70), low level of knowledge about COVID-19 (β coefficient = 1.87, 95% CI: 1.09, 3.41), and substance use (β coefficient = 1.7, 95% CI: 1.23, 6.47) were positively associated with mean overt aggression score. Conclusion The present study revealed that suicidal and aggressive behaviors were prevalent with significant correlates. Therefore, it is important and required to provide focused mental health and psycho-social services for the selected and high-risk populations such as those in quarantine and isolation centers for being suspected.
Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial

Molecular hydrogen (H2) is a versatile therapeutic agent. H2 gas inhalation is reportedly safe and has a positive impact on a range of illnesses, including Alzheimer’s disease (AD). Herein, we investigated the effects of 4 weeks of H2 gas inhalation on community-dwelling adults of various ages. Fifty-four participants, including those who dropped out (5%), were screened and enrolled. The selected participants were treated as a single group without randomization. We evaluated the association between total and differential white blood cell (WBC) counts and AD risk at individual levels after 4 weeks of H2 gas inhalation treatment. The total and differential WBC counts were not adversely affected after H2 gas inhalation, indicating that it was safe and well tolerated. Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment. Furthermore, evaluation of dementia-related biomarkers, such as beta-site APP cleaving enzyme 1 (BACE-1), amyloid beta (Aβ), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases. Collectively, our results indicate that H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction in community-dwelling adults of different ages.