Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Inactivation of Peroxiredoxin-I Impairs the Growth of Human Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with few therapeutic options. The identification of new promising targets is, therefore, an urgent need. Using available transcriptomic datasets, we first found that Peroxiredoxin-1 gene (PRDX1) expression was significantly increased in human pancreatic tumors, but not in the other gastrointestinal cancers; its high expression correlated with shortened patient survival. We confirmed by immunostaining on mouse pancreata the increased Peroxiredoxin-I protein (PRX-I) expression in pancreatic neoplastic lesions and PDAC. To question the role of PRX-I in pancreatic cancer, we genetically inactivated its expression in multiple human PDAC cell lines, using siRNA and CRISPR/Cas9. In both strategies, PRX-I ablation led to reduced survival of PDAC cells. This was mainly due to an increase in the production of reactive oxygen species (ROS), accumulation of oxidative DNA damage (i.e., 8-oxoguanine), and cell cycle blockade at G2/M. Finally, we found that PRX-I ablation disrupts the autophagic flux in PDAC cells, which is essential for their survival. This proof-of-concept study supports a pro-oncogenic role for PRX-I in PDAC.
Submandibular Push Exercise Using Visual Feedback from a Pressure Sensor in Patients with Swallowing Difficulties: A Pilot Study

Objectives: We aimed to determine the usefulness and effectiveness of a submandibular push exercise with visual feedback from a pressure sensor in patients with dysphagia through continuous exercise sessions. Methods: Twelve patients with dysphagia of various etiologies were included. A total of five exercise sessions (every 3 or 4 days) over three weeks were conducted. During the submandibular push exercise, patients were instructed to maintain a maximum force for 3 s, repeated for 1 min to measure the number of exercises, the maximum pressure, and the area of the pressure-time graph. We statistically compared the values of each exercise trial. Results: Among the 12 patients, eight completed the exercise sessions. As the number of exercise trials increased, the maximum pressure and the area in the pressure-time graph showed a significant increase compared to the previous attempt (p < 0.05). The maximum pressure and the area of the pressure-time graph improved from the first to the fourth session (p < 0.05). The values were maintained after the fourth session, and there was no significant difference between the fourth and the fifth exercise (p > 0.05). There was no significant difference between successful and non-successful groups, except for the Modified Barthel Index (p < 0.05). Conclusion: Through repetitive exercise training, the submandibular push exercise using visual feedback from a pressure sensor can be applied as an exercise method to strengthen swallowing related muscles, such as the suprahyoid and infrahyoid muscles. However, additional studies including more patients and a long-term study period are warranted to evaluate the effects of the exercise for improvement of dysphagia.
Human Mitoribosome Biogenesis and Its Emerging Links to Disease

Mammalian mitochondrial ribosomes (mitoribosomes) synthesize a small subset of proteins, which are essential components of the oxidative phosphorylation machinery. Therefore, their function is of fundamental importance to cellular metabolism. The assembly of mitoribosomes is a complex process that progresses through numerous maturation and protein-binding events coordinated by the actions of several assembly factors. Dysregulation of mitoribosome production is increasingly recognized as a contributor to metabolic and neurodegenerative diseases. In recent years, mutations in multiple components of the mitoribosome assembly machinery have been associated with a range of human pathologies, highlighting their importance to cell function and health. Here, we provide a review of our current understanding of mitoribosome biogenesis, highlighting the key factors involved in this process and the growing number of mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors that lead to human disease.
Exploring the behavioral determinants of COVID-19 vaccine acceptance among an urban population in Bangladesh: Implications for behavior change interventions

Background: While vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need understanding to implicate appropriate interventions. The aim of this study was to assess the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the uptake of COVID-19 vaccines in Bangladesh. Methods: We employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines. Results: COVID-19 vaccine Acceptors in Dhaka were different from Non-acceptors in terms of many of their beliefs and responses. The behavioral determinants associated with the behavior included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the Health Belief Model, beliefs about the disease itself were highly correlated with vaccine acceptance, although not the only determinant. Other responses of Acceptors provide clues such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols as to ways to make it easier to boost acceptance. Conclusion: An effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. The national plans on COVID-19 vaccination should adopt culturally and community label acceptable and appropriate evidence-based behavior change interventions strategies to promote high vaccination coverage and acceptance in all societal structures across the country.
Dealing with distress from the COVID‐19 pandemic: Mental health stressors and coping strategies in vulnerable latinx communities

Abstract Distress secondary to the COVID‐19 pandemic has been substantial, especially in vulnerable Latinx communities who are carrying an undue share of the pandemic‐related social, health and economic burden in the United States. In collaboration with 43 community health workers (CHWs) and Promotor/as serving the needs of underserved Latinx communities in South Texas and guided by principles of community‐based participatory research (CBPR), the purpose of this study was to identify relevant mental health stressors and related consequences, and to identify strategies for coping with distress among underserved Latinx communities during the COVID‐19 pandemic. Data were collected on July 2020 using mixed methods to obtain more in‐depth information. Surveys were administered, and three focus groups were conducted. Quantitative data were analysed using descriptive statistics, whereas qualitative data were analysed systematically by starting with a priori questions and themes followed by data categorisation, reduction, display and conclusion drawing. Results showed six themes related to mental health stressors including economics (e.g., job insecurity), immigration (e.g., undocumented status), misinformation, family stress (e.g., changes in family dynamics and the home environment), health (e.g., limited healthcare access) and social isolation. Coping skills of the community were categorised into four themes with multiple codes including behavioural strategies (e.g., identifying reliable information), cognitive strategies (e.g., collectivistic thinking), social support and spirituality. Findings indicate that underserved Latinx communities are dealing with substantial distress and mental health concerns secondary to the COVID‐19 pandemic; yet these are resilient communities. Implications of these findings can inform development of resources, interventions, best practices and training avenues to address the mental health needs of underserved Latinx communities, while considering relevant cultural and contextual factors that may influence their effectiveness.
An Extended Evaluation of Academic Encouragement Scale for Adolescents

The Academic Encouragement Scale (AES) evaluates academic encouragement received from someone whom the student respects. This study reported the psychometric properties of the AES among 1602 Chinese adolescents. The results of confirmatory factor analysis (CFA) supported a two-factor structure of the AES (i.e., challenge-focused encouragement (CFE) and potential-focused encouragement). Multigroup CFA indicated that the AES showed measurement and structural invariance across gender groups. Each factor of the AES showed adequate internal consistency reliability (α > .84) and test–retest stability (r > .75). Correlation analyses demonstrated that the AES subscales were significantly related to academic self-efficacy, hope, and social connectedness in the expected directions, which yielded evidence for the concurrent validity of the AES. Results indicated that the CFE factor significantly predicted academic achievement, but the potential-focused encouragement factor did not significantly predict academic achievement. Overall, the findings support the use of the AES among adolescents.
Biogenic Silver Nanoparticles as a Strategy in the Fight Against Multi-Resistant Salmonella enterica Isolated From Dairy Calves

Infectious diseases are one of the most important health problems worldwide, one of the main causes being the development of multi-resistant microorganisms. Likewise, the zoonotic potential of some pathogens and their ability to transfer resistance mechanisms, reduce the therapeutic options in both humans and animals. Salmonella enterica is an important pathogen that affects a wide range of animal species and humans, being Salmonella Typhimurium one of the most frequent serotypes affecting cattle, causing enteritis, diarrhea, and septicemia. The search for alternative therapeutic approaches has gained importance since the emergence of multidrug resistance to antibiotics and periodic outbreaks of salmonellosis. In this sense, the discovery of new drugs and the development of new strategies, such as the use of nanoparticles with antimicrobial activity, are very promising. The aim of this work was the extracellular production of biogenic silver nanoparticles using fungal extracts and the evaluation of their antimicrobial activity against resistant and multi-resistant Salmonella Typhimurium strains. We here demonstrated the potential of the biogenic nanoparticles as effective bacteriostatic and bactericidal agents for use in biomedical applications. In addition, Confocal Raman Microscopy and Atomic Force Microscopy were used to advance the understanding of the antimicrobial mechanism of biogenic nanoparticles against these pathogenic strains, the results of which suggested that the nanoparticles produced damage in several bacterial cell structures.
The Association Between Relationship Events and Experiences and Partner Evaluations: An Ideal Standards Perspective

Drawing on the Ideal Standards Model, the current study investigated whether the relationship events and experiences that occur on a given day in romantic relationships were associated with partner evaluations. Individuals in a current romantic relationship (N = 104) completed daily measures of positive and negative relationship events and experiences and partner evaluations for seven consecutive days. As hypothesized, findings demonstrated that on a given day negative relationship events and experiences were associated with evaluating partners as falling short of mate ideals, while positive relationship events and experiences were associated with evaluating partners as more closely meeting ideals. The findings demonstrate the importance of the relational context in evaluations of a partner against ideal standards.
Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine

The ability to reliably repair spinal cord injuries (SCI) will be one of the greatest human achievements realized in regenerative medicine. Until recently, the cellular path to this goal has been challenging. However, as detailed developmental principles are revealed in mouse and human models, their application in the stem cell community brings trunk and spine embryology into efforts to advance human regenerative medicine. New models of posterior embryo development identify neuromesodermal progenitors (NMPs) as a major bifurcation point in generating the spinal cord and somites and is leading to production of cell types with the full range of axial identities critical for repair of trunk and spine disorders. This is coupled with organoid technologies including assembloids, circuitoids, and gastruloids. We describe a paradigm for applying developmental principles towards the goal of cell-based restorative therapies to enable reproducible and effective near-term clinical interventions.
Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease

Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves’ disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.
Patient Education for Kidney Failure Treatment: A Mixed-Methods Study.

RATIONALE & OBJECTIVE Education programs are needed for people with advanced chronic kidney disease (CKD) to understand kidney failure treatment options and participate in shared decision-making (SDM). Little is known about the content and accessibility of current education programs, and whether they support SDM. STUDY DESIGN Stakeholder-engaged, mixed-methods design incorporating qualitative observations and interviews, and a quantitative content analysis of slide presentations. SETTING & PARTICIPANTS 4 sites in Boston, Chicago, Portland (Maine), and San Diego. ANALYTICAL APPROACH Thematic analysis based on the Ottawa Framework (observations and interviews) and descriptive statistical analysis (slide presentations). RESULTS Data were collected from observations of 9 education sessions, 5 semi-structured interviews with educators, and 133 educational slide presentations. Sites offered group classes or one-on-one sessions. Development, quality, and accuracy of educational materials varied widely. Educators emphasized dialysis (often in-center hemodialysis), with little mention of conservative management. Educators reported patients were often referred too late to education sessions and that some patients become overwhelmed if they learn of the implications of kidney failure in a group setting. Commonly, sessions were general and did not provide opportunities for tailored information most supportive of SDM. Few nephrologists were involved in education sessions or aware of the educational content. Content gaps included prognosis, decision support, mental health and cognition, advanced care planning, cost, and diet. Slide presentations used did not consistently reflect best practices related to health literacy. LIMITATIONS Findings may not be broadly generalizable. CONCLUSION Education sessions focused on kidney failure options do not consistently follow best practices related to health literacy or for supporting shared decision-making. To facilitate SDM, establishing expectations for kidney failure treatment options should be clearly defined and integrated into the clinical workflow. Addressing content gaps, health literacy, and communication with nephrologists are necessary steps for improving patient education in the setting of advanced CKD.
The Potential Role of Awe for Depression: Reassembling the Puzzle

Recently, interest in the unique pathways linking discrete positive emotions to specific health outcomes has gained increasing attention, but the role of awe is yet to be elucidated. Awe is a complex and transformative emotion that can restructure individuals' mental frames so deeply that it could be considered a therapeutic asset for major mental health major issues, including depression. Despite sparse evidence showing a potential connection between depression and awe, this link has not been combined into a proposal resulting in specific intervention guidelines. The aim of this perspective was three-fold: (i) to provide a new unifying model of awe's functioning—the Matryoshka model; (ii) to show systematic and explicit connections between this emotion and depression; and (iii) to suggest specific guidelines of intervention utilizing the potential therapeutic role of awe for mental health, specifically for depression. This theoretical endeavor in its entirety has been framed within the health domain.
Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

Human liver stem cells (HLSCs) were described for the first time in 2006 as a new stem cell population derived from healthy human livers. Like mesenchymal stromal cells, HLSCs exhibit multipotent and immunomodulatory properties. HLSCs can differentiate into several lineages under defined in vitro conditions, such as mature hepatocytes, osteocytes, endothelial cells, and islet-like cell organoids. Over the years, HLSCs have been shown to contribute to tissue repair and regeneration in different in vivo models, leading to more than five granted patents and over 15 peer reviewed scientific articles elucidating their potential therapeutic role in various experimental pathologies. In addition, HLSCs have recently completed a Phase 1 study evaluating their safety post intrahepatic injection in infants with inherited neonatal onset hyperammonemia. Even though a lot of progress has been made in understanding HLSCs over the past years, some important questions regarding the mechanisms of action remain to be elucidated. Among the mechanisms of interaction of HLSCs with their environment, a paracrine interface has emerged involving extracellular vesicles (EVs) as vehicles for transferring active biological materials. In our group, the EVs derived from HLSCs have been studied in vitro as well as in vivo. Our attention has mainly been focused on understanding the in vivo ability of HLSC–derived EVs as modulators of tissue regeneration, inflammation, fibrosis, and tumor growth. This review article aims to discuss in detail the role of HLSCs and HLSC-EVs in these processes and their possible future therapeutic applications.
Three-Dimensional Live Imaging of Bovine Preimplantation Embryos: A New Method for IVF Embryo Evaluation

Conception rates for transferred bovine embryos are lower than those for artificial insemination. Embryo transfer (ET) is widely used in cattle but many of the transferred embryos fail to develop, thus, a more effective method for selecting bovine embryos suitable for ET is required. To evaluate the developmental potential of bovine preimplantation embryos (2-cell stage embryos and blastocysts), we have used the non-invasive method of optical coherence tomography (OCT) to obtain live images. The images were used to evaluate 22 parameters of blastocysts, such as the volume of the inner cell mass and the thicknesses of the trophectoderm (TE). Bovine embryos were obtained by in vitro fertilization (IVF) of the cumulus-oocyte complexes aspirated by ovum pick-up from Japanese Black cattle. The quality of the blastocysts was examined under an inverted microscope and all were confirmed to be Code1 according to the International Embryo Transfer Society standards for embryo evaluation. The OCT images of embryos were taken at the 2-cell and blastocyst stages prior to the transfer. In OCT, the embryos were irradiated with near-infrared light for a few minutes to capture three-dimensional images. Nuclei of the 2-cell stage embryos were clearly observed by OCT, and polynuclear cells at the 2-cell stage were also clearly found. With OCT, we were able to observe embryos at the blastocyst stage and evaluate their parameters. The conception rate following OCT (15/30; 50%) is typical for ETs and no newborn calves showed neonatal overgrowth or died, indicating that the OCT did not adversely affect the ET. A principal components analysis was unable to identify the parameters associated with successful pregnancy, while by using hierarchical clustering analysis, TE volume has been suggested to be one of the parameters for the evaluation of bovine embryo. The present results show that OCT imaging can be used to investigate time-dependent changes of IVF embryos. With further improvements, it should be useful for selecting high-quality embryos for transfer.