Miracle-dz/UniFAR-FTUs huggingface dataset:
The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice

Molecular alterations of the Ataxia-telangiectasia (AT) gene are frequently detected in breast cancer (BC), with an incidence ranging up to 40%. The mutated form, the Ataxia-telangiectasia mutated (ATM) gene, is involved in cell cycle control, apoptosis, oxidative stress, and telomere maintenance, and its role as a risk factor for cancer development is well established. Recent studies have confirmed that some variants of ATM are associated with an increased risk of BC development and a worse prognosis. Thus, many patients harboring ATM mutations develop intermediate- and high-grade disease, and there is a higher rate of lymph node metastatic involvement. The evidence concerning a correlation of ATM gene mutations and the efficacy of therapeutic strategies in BC management are controversial. In fact, ATM mutations may sensitize cancer cells to platinum-derived drugs, as BRCA1/2 mutations do, whereas their implications in objective responses to hormonal therapy or target-based agents are not well defined. Herein, we conducted a review of the role of ATM gene mutations in BC development, prognosis, and different treatment strategies.
Monkeying around with MAIT Cells: Studying the Role of MAIT Cells in SIV and Mtb Co-Infection

There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that target and destroy bacterially-infected cells and may contribute to the control of Mtb infection. Studies examining MAIT cells in human Mtb infection are commonly performed using peripheral blood samples. However, because Mtb infection occurs primarily in lung tissue and lung-associated lymph nodes, these studies may not be fully translatable to the tissues. Additionally, studies longitudinally examining MAIT cell dynamics during HIV/Mtb co-infection are rare, and lung and lymph node tissue samples from HIV+ patients are typically unavailable. Nonhuman primates (NHP) provide a model system to characterize MAIT cell activity during Mtb infection, both in Simian Immunodeficiency Virus (SIV)-infected and SIV-naïve animals. Using NHPs allows for a more comprehensive understanding of tissue-based MAIT cell dynamics during infection with both pathogens. NHP SIV and Mtb infection is similar to human HIV and Mtb infection, and MAIT cells are phenotypically similar in humans and NHPs. Here, we discuss current knowledge surrounding MAIT cells in SIV and Mtb infection, how SIV infection impairs MAIT cell function during Mtb co-infection, and knowledge gaps to address.
Recognition and reporting of neglected tropical diseases by primary health care workers in Ibadan, Nigeria

Introduction neglected tropical diseases (NTDs) are serious public health problem worldwide. Primary healthcare (PHC) workers are important in the prevention and control of these diseases. Accurate diagnosis and timely reporting are essential for effective public health response. The study assessed the knowledge of PHC workers on NTDs and identified factors influencing its recognition and reporting. Methods the study was a hospital based cross-sectional survey. A multistage sampling technique was used to select 327 healthcare workers from sixty-six PHC facilities in Ibadan, Oyo State, Nigeria. A semi-structured, self-administered questionnaire was used to elicit information on respondent´s socio-demographic characteristics, knowledge, recognition and reporting of NTDs. Data analysis were done using independent sample t-test, analysis of variance and logistic regression with p-value set at 0.05. Results one hundred and eighty seven (57.2%) respondents had good knowledge of NTDs. The NTDs most known were; Schistosomiasis (78%), Rabies (64.5%), and Onchocerciasis (57.2%). Urban healthcare workers had higher knowledge score on NTDs (p= 0.018). Young age (AOR= 3.40, CI= 1.20 -9.63), length of practice (AOR=4.65, CI= 1.20-18.09) and previous training on NTDs (AOR = 7.09, CI= 3.15 - 15.93) significantly predicted NTDs recognition, while availability of reporting forms (AOR= 3.17, CI=1.07 - 9.35), training on disease reporting (AOR= 3.41, CI= 11.17 - 9.92) and feedback on previous diseases reported (AOR= 4.12, CI= 1.32-12.80) were significant predictors of reporting NTDs. Conclusion the healthcare workers knowledge on NTDs was inadequate. Periodic training and continued education on NTDs are recommended. PHC workers also require supportive supervision.
Identification, Comparison and Classification of Volatile Compounds in Peels of 40 Apple Cultivars by HS–SPME with GC–MS

Aroma is an important quality indicator for apples and has a great influence on the overall flavour and consumer acceptance. However, the information of the aroma volatile compounds in apple peels is largely unknown. In this study, evaluation of volatile compounds in peels of 40 apple cultivars was carried out using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). A total of 78 volatile compounds were identified, including 47 esters, 12 aldehydes, 5 alcohols, 3 ketones, 1 acid and 10 others. Eight volatile compounds were common in all apple cultivars. Cultivar Changfu No. 2 contained the highest number of volatile compounds (47), while Qinyue contained the least (20). Honey Crisps had the highest volatile content, at 27,813.56 ± 2310.07 μg/kg FW, while Huashuo had the lowest volatile content, at 2041.27 ± 120.36 μg/kg FW. Principal component analysis (PCA) clustered the 40 apple cultivars into five groups. Aroma is cultivar-specific, volatile compounds of hexyl butyrate, hexyl 2-methylbutyrate and hexyl hexanoate, together with hexanal, (E)-2-hexenal, 1-hexanol, estragole and α-farnesene could be proposed for apple cultivar classification in the future.
Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

We aimed to clarify whether a steal ‘phenomenon’ exists by investigating if uptake of ‘prostate specific membrane antigen’ (PSMA) in prostate tumor tissue correlates with the uptake in healthy tissue. Patients with prostate cancer referred for a [68Ga]Ga-PSMA-11 PET/CT were identified retrospectively. Semi-automated quantitative image analysis was performed; fractional healthy tissue [68Ga]Ga-PSMA-11 uptake volume (HT-PSMA (SUV*cm3)) in the lacrimal, submandibular, and parotid glands, and kidneys, and the fractional total lesion [68Ga]Ga-PSMA-11 uptake volume (TL-PSMA (SUV*cm3)) of prostate cancer were used. Ninety-two patients, age 78 ± 8 years, were analyzed. Median TL-PSMA was 703.37 SUV*cm3 (IQR 119.56–2778.20), median HT-PSMA of the lacrimal, submandibular, and parotid glands, and kidneys was: 13.69 (IQR 7.29–19.06), 194.75 (IQR 133.67–276.53), 552.54 (IQR 379.98–737.16), and 8092.75 SUV*cm3 (IQR 5793.02–11,385.86), respectively. A significant (p-value ≤ 0.001) but weak–moderate correlation was found between the TL-PSMA and HT-PSMA of the parotid- and submandibular glands, and kidneys (correlation coefficient of −0.447, −0.345, and −0.394, respectively). No correlation was found between TL-PSMA and HT-PSMA of the lacrimal glands. The existence of a ‘steal’ phenomenon cannot be confirmed in this study. Healthy tissue uptake of [68Ga]Ga-PSMA-11 is only partially influenced by TL-PSMA. Thus, modification of therapeutic PSMA activity should not be adjusted based on TL-PSMA alone.
Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems

The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC50 value (the concentration resulting in 50% activation) was determined. The tested compounds can be ranked as follows: tCA > FA > SA with AC50 = 0.10, 0.39, 0.69 mM, respectively. Strong synergism was found between FA and SA. The activatory effects of all tested compounds may result from interaction with the TPO allosteric site. It was proposed that conformational change resulting from activator binding to TPO allosteric pocket results from the flexibility of a nearby loop formed by residues Val352-Tyr363. All compounds act as uncompetitive LOX inhibitors. The most effective were tCA and SA, whereas the weakest was FA (IC50 = 0.009 mM and IC50 0.027 mM, respectively). In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested. FA/tCA and FA/SA acted synergistically, whereas tCA/SA demonstrated antagonism. The highest antiradical activity was found in the case of SA (IC50 = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture.
Recovery of Chloride Penetration Resistance of Cement-Based Composites Due to Self-Healing of Cracks

This study proposed a method of applying coating on uncracked surfaces of test specimens in the electrical migration–diffusion test for the evaluation of the chloride penetration resistance of cracked cement-based composites. It was shown that, by applying the proposed method, the recovery of the chloride penetration resistance from self-healing of cracks can be evaluated more accurately because the application of surface coating reduces the test time and the error introduced by over-simplification. Based on observations of the self-healing-induced recovery of chloride penetration resistance, a phenomenological model for predicting the progress of crack self-healing in cement-based composites was suggested. This model is expected to evaluate the chloride penetration resistance more accurately in actual concrete structures with cracks.
Parental Nonstandard Work Schedules and Child Development: Evidence from Dual-Earner Families in Hong Kong

With the emergence of 24/7 economies, the practice of working nonstandard schedules has become increasingly common. This trend raises a concern about how parental nonstandard work schedules affect child development outcomes. Using data from dual-earner families with young children (age 5–6) in Hong Kong, this study examined the association between parental work schedules and child development. It also examined under what conditions parental nonstandard work schedules affect child development, with a focus on the moderating role of family income. Results showed that paternal nonstandard work schedules were negatively associated with overall child development. This association was particularly salient among low-income families. By contrast, maternal nonstandard work schedules were not associated with child development outcomes. These findings suggest that it is important to equip parents, in particular low-income fathers, to address challenges resulting from their nonstandard work schedules.
Protective effects of quercetin against hyperglycemia-induced oxidative stress in hepatic HepG2 cell line

Objective: Hyperglycemia is a severe consequence of diabetes mellitus (DM). Throughinduction of oxidative stress, it plays a major role in the pathogenesis of several complications in DM. Therefore, new strategies and antioxidants should be implemented inthe treatment of DM. Quercetin is a flavonoid with strong antioxidant capacity found dominantly in vegetables, fruits, leaves, and grains. The current study aimed to investigate quercetin protective effects under D-glucose-induced oxidative stress by assessing antioxidant defense enzymes inHepG2 cells as an in vitro model. Materials and Methods: HepG2 cells were cultured with different concentrations of D-glucose (5.5, 30 and 50 mM) and/or 25 μM quercetin for 48 and 72 hr, respectively. The effect of treatments on cellular integrity, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) activity, andcellular levels of glutathione (GSH) and malondialdehyde (MDA) wasdetermined. Results: D-glucose had various effects on intracellular antioxidant defense atdifferent doses and time-points and quercetin could attenuate oxidative stress and modulate antioxidant defenses. Conclusion: The results of this study indicated that flavonoid quercetin could be proposed as an agent protecting hepatic HepG2 cells against oxidative stress associated with hyperglycemia.
Ferulic Acid-Loaded Polymeric Nanoparticles for Potential Ocular Delivery

Ferulic acid (FA) is an antioxidant compound that can prevent ROS-related diseases, but due to its poor solubility, therapeutic efficacy is limited. One strategy to improve the bioavailability is nanomedicine. In the following study, FA delivery through polymeric nanoparticles (NPs) consisting of polylactic acid (NPA) and poly(lactic-co-glycolic acid) (NPB) is proposed. To verify the absence of cytotoxicity of blank carriers, a preliminary in vitro assay was performed on retinal pericytes and endothelial cells. FA-loaded NPs were subjected to purification studies and the physico-hemical properties were analyzed by photon correlation spectroscopy. Encapsulation efficiency and in vitro release studies were assessed through high performance liquid chromatography. To maintain the integrity of the systems, nanoformulations were cryoprotected and freeze-dried. Morphology was evaluated by a scanning electron microscope. Physico-chemical stability of resuspended nanosystems was monitored during 28 days of storage at 5 °C. Thermal analysis and Fourier-transform infrared spectroscopy were performed to characterize drug state in the systems. Results showed homogeneous particle populations, a suitable mean size for ocular delivery, drug loading ranging from 64.86 to 75.16%, and a controlled release profile. The obtained systems could be promising carriers for ocular drug delivery, legitimating further studies on FA-loaded NPs to confirm efficacy and safety in vitro.
CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A

TMEM16A, a Ca2+-activated chloride channel (CaCC), and its regulator, CLCA1, are associated with inflammatory airway disease and goblet cell metaplasia. CLCA1 is a secreted protein with protease activity that was demonstrated to enhance membrane expression of TMEM16A. Expression of CLCA1 is particularly enhanced in goblet cell metaplasia and is associated with various lung diseases. However, mice lacking expression of CLCA1 showed the same degree of mucous cell metaplasia and airway hyperreactivity as asthmatic wild-type mice. To gain more insight into the role of CLCA1, we applied secreted N-CLCA1, produced in vitro, to mice in vivo using intratracheal instillation. We observed no obvious upregulation of TMEM16A membrane expression by CLCA1 and no differences in ATP-induced short circuit currents (Iscs). However, intraluminal mucus accumulation was observed by treatment with N-CLCA1 that was not seen in control animals. The effects of N-CLCA1 were augmented in ovalbumin-sensitized mice. Mucus production induced by N-CLCA1 in polarized BCi-NS1 human airway epithelial cells was dependent on TMEM16A expression. IL-13 upregulated expression of CLCA1 and enhanced mucus production, however, without enhancing purinergic activation of Isc. In contrast to polarized airway epithelial cells and mouse airways, which express very low levels of TMEM16A, nonpolarized airway cells express large amounts of TMEM16A protein and show strong CaCC. The present data show an only limited contribution of TMEM16A to airway ion secretion but suggest a significant role of both CLCA1 and TMEM16A for airway mucus secretion.
Ergonomic Risk Factors of Teleworking in Ecuador during the COVID-19 Pandemic: A Cross-Sectional Study

Due to the COVID-19 global pandemic, guidelines for people’s confinement have been implemented to prevent the disease’s spread. As a result of this, companies have implemented teleworking as an emerging way to work from home using information technology. This cross-sectional study was conducted in Ecuador, with a sample of 204 teleworkers in the city of Quito. The results show that the teleworkers rearranged their bedrooms to carry out their activities. The respondents in each age group stated they did not perceive more significant ailments than those experienced before beginning teleworking. The relationships between the variables were analyzed utilizing the Chi-Square test and Fisher’s exact test, finding a relationship between neck ailments and age of p = 0.031 * and between arm/forearm ailments of p = 0.032 *. This study contributes to a greater understanding of the ergonomic situation of the teleworkers and provides us with information to mitigate the ergonomic risks to which they are exposed.
Glioblastoma Metabolomics—In Vitro Studies

In 2016, the WHO introduced new guidelines for the diagnosis of brain gliomas based on new genomic markers. The addition of these new markers to the pre-existing diagnostic methods provided a new level of precision for the diagnosis of glioma and the prediction of treatment effectiveness. Yet, despite this new classification tool, glioblastoma (GBM), a grade IV glioma, continues to have one of the highest mortality rates among central nervous system tumors. Metabolomics is a particularly promising tool for the analysis of GBM tumors and potential methods of treating them, as it is the only “omics” approach that is capable of providing a metabolic signature of a tumor’s phenotype. With careful experimental design, cell cultures can be a useful matrix in GBM metabolomics, as they ensure stable conditions and, under proper conditions, are capable of capturing different tumor phenotypes. This paper reviews in vitro metabolomic profiling studies of high-grade gliomas, with a particular focus on sample-preparation techniques, crucial metabolites identified, cell culture conditions, in vitro-in vivo extrapolation, and pharmacometabolomics. Ultimately, this review aims to elucidate potential future directions for in vitro GBM metabolomics.
The Ratio of GrzB+ − FoxP3+ over CD3+ T Cells as a Potential Predictor of Response to Nivolumab in Patients with Metastatic Melanoma

Simple Summary Despite the recent success of immunotherapy in the treatment of malignant melanoma, many patients still do not benefit from these treatments, due to their failure to activate an antitumor immune response them. There is therefore a need to select patients who can truly benefit from these treatments. We have focused our study on immune cells present in the tumor microenvironment, and we have developed a formula (ratio) that correlates with the response to anti-PD1 therapy and progression-free and overall survival, based on the numerical difference between GRZB+ and FOXP3+ cells over the total CD3+ lymphocytes. This developed ratio could be useful to better select patients that may or may not benefit from anti-PD-1 treatment. Abstract The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.e., cancer-associated fibroblasts, keratinocytes, adipocytes, extracellular matrix, etc.) are essential for effective antitumor immunotherapy, suggesting the need to define an immune score model which can help to predict an efficient immunotherapeutic response. In this study, we performed a multiplex immunostaining of CD3, FOXP3 and GRZB on both primary and unmatched in-transit metastatic melanoma lesions and defined a novel ratio between different lymphocyte subpopulations, demonstrating its potential prognostic role for cancer immunotherapy. The application of the suggested ratio can be useful for the stratification of melanoma patients that may or may not benefit from anti-PD-1 treatment.
Deficits in Early Sensory and Cognitive Processing Are Related to Phase and Nonphase EEG Activity in Multiple Sclerosis Patients

Currently, there is scarce knowledge about the relation between spectral bands modulations and the basis of cognitive impairment in multiple sclerosis (MS). In this sense, analyzing the evoked or phase activity can confirm results from traditional event-related potential (ERP) studies. However, studying the induced or nonphase activity may be necessary to elucidate hidden compensatory or affected cognitive mechanisms. In this study, 30 remitting-relapsing multiple sclerosis patients and 30 healthy controls (HCs) matched in sociodemographic variables performed a visual oddball task. The main goal was to analyze phase and nonphase alpha and gamma bands by applying temporal spectral evolution (TSE) and its potential relation with cognitive impairment in these patients. The behavioural results showed slower reaction time and poorer accuracy in MS patients compared to controls. In contrast, the time-frequency analysis of electroencephalography (EEG) revealed a delay in latency and lower amplitude in MS patients in evoked and induced alpha compared to controls. With respect to the gamma band, there were no differences between the groups. In summary, MS patients showed deficits in early sensorial (evoked alpha activity) and cognitive processing (induced alpha activity in longer latencies), whereas the induced gamma band supported the hypothesis of its role in translation of attentional focus (induced activity) and did not show strong activity in this paradigm (visual oddball).
Herpes Simplex Virus Type 2 Mucin-Like Glycoprotein mgG Promotes Virus Release from the Surface of Infected Cells

The contribution of virus components to liberation of herpes simplex virus type 2 (HSV-2) progeny virions from the surface of infected cells is poorly understood. We report that the HSV-2 mutant deficient in the expression of a mucin-like membrane-associated glycoprotein G (mgG) exhibited defect in the release of progeny virions from infected cells manifested by ~2 orders of magnitude decreased amount of infectious virus in a culture medium as compared to native HSV-2. Electron microscopy revealed that the mgG deficient virions were produced in infected cells and present at the cell surface. These virions could be forcibly liberated to a nearly native HSV-2 level by the treatment of cells with glycosaminoglycan (GAG)-mimicking oligosaccharides. Comparative assessment of the interaction of mutant and native virions with surface-immobilized chondroitin sulfate GAG chains revealed that while the mutant virions associated with GAGs ~fourfold more extensively, the lateral mobility of bound virions was much poorer than that of native virions. These data indicate that the mgG of HSV-2 balances the virus interaction with GAG chains, a feature critical to prevent trapping of the progeny virions at the surface of infected cells.