Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.
Demographic and Habitual Factors of Periodontal Disease among South Indian Adults

The aim of this study was to evaluate the performance of a set of sociodemographic and habits measures on estimating periodontal disease among south Indian adults. This cross-sectional study was carried out among 288 individuals above 18 years old in Tamil Nadu, India. The outcome of the study was periodontal disease, measured by WHO criteria. The covariates were age, ethnicity, smoking and alcohol habit. The assessment of factors predicting periodontal disease was carried out by multiple logistic regression analysis using R version 3.6. 1. The demographic factors like age group (AOR = 3.56; 95% CI 1.69–7.85), ethnicity (AOR = 6.07; 95% CI 2.27–18.37), non-alcoholic (AOR = 0.31; 95% CI 0.13–0.64) and non-smoking (AOR = 0.33; 95% CI 0.15–0.67) were found to be associated with the outcome. The maximum log likelihood estimate value was −30.5 and AIC was 385 for the final model, respectively. Receiver operating characteristic (ROC) curve for the periodontal disease was 0.737. We can conclude that sociodemographic factors and habits were useful for predicting periodontal diseases.
Cloud Computing Based Immunopeptidomics Utilizing Community Curated Variant Libraries Simplifies and Improves Neo-Antigen Discovery in Metastatic Melanoma

Simple Summary Peptides expressed on the cell surface can be used to distinguish between diseased and healthy cells and for precision drug targeting. Ideal targets in cancer diagnostics and therapeutic development are the result of altered peptide sequences that make it to the surface as expressed neoantigens. Identifying these peptides requires both genomics and proteomics sequencing technologies, which makes the process both expensive and challenging. We present an alternative solution where cloud computing can be used to improve and simplify current approaches. Abstract Unique peptide neo-antigens presented on the cell surface are attractive targets for researchers in nearly all areas of personalized medicine. Cells presenting peptides with mutated or other non-canonical sequences can be utilized for both targeted therapies and diagnostics. Today’s state-of-the-art pipelines utilize complementary proteogenomic approaches where RNA or ribosomal sequencing data helps to create libraries from which tandem mass spectrometry data can be compared. In this study, we present an alternative approach whereby cloud computing is utilized to power neo-antigen searches against community curated databases containing more than 7 million human sequence variants. Using these expansive databases of high-quality sequences as a reference, we reanalyze the original data from two previously reported studies to identify neo-antigen targets in metastatic melanoma. Using our approach, we identify 79 percent of the non-canonical peptides reported by previous genomic analyses of these files. Furthermore, we report 18-fold more non-canonical peptides than previously reported. The novel neo-antigens we report herein can be corroborated by secondary analyses such as high predicted binding affinity, when analyzed by well-established tools such as NetMHC. Finally, we report 738 non-canonical peptides shared by at least five patient samples, and 3258 shared across the two studies. This illustrates the depth of data that is present, but typically missed by lower statistical power proteogenomic approaches. This large list of shared peptides across the two studies, their annotation, non-canonical origin, as well as MS/MS spectra from the two studies are made available on a web portal for community analysis.
Moral injury and mental health outcomes among Israeli health and social care workers during the COVID-19 pandemic: a latent class analysis approach

ABSTRACT Background: The COVID-19 pandemic poses unique challenges to health and social care workers (HSCWs) who face morally challenging and life-threatening decisions. Following exposure to events that transgress moral beliefs and expectations, HSCWs might experience psychological, social, and spiritual problems referred to as Moral Injury (MI). Objective: The objectives of this study were to examine patterns of exposure to potentially morally injurious events (PMIEs) among HSCWs and their associations with MI, mental health outcomes and psychological correlates. Method: A sample of 296 Israeli HSCWs volunteered to complete a cross-sectional electronic survey with validated self-report questionnaires in February and March 2021. Latent Class Analysis (LCA) was used to identify classes characterized by unique patterns of exposure to PMIEs. Socio-demographic, work and COVID-related variables were used to predict patterns of exposure to PMIEs, and differences in mental-health outcomes and psychological correlates between classes were assessed. Results: Three subgroups were identified: ‘high exposure’ (19.5%), ‘betrayal-only’ (31.3%), and ‘minimal exposure’ (49.4%). Perceived stress increases the odds for inclusion in the ‘high exposure’ and ‘betrayal-only’ classes. Participants in both the High Exposure class and the betrayal-only classes reported higher levels of depressive, anxiety, posttraumatic and more moral injury symptoms as compared to the ‘minimal exposure’ class. Importantly, both ‘high exposure’ and ‘betrayal-only’ classes reported lower levels of self-compassion and higher levels of self-criticism, relative to those in the ‘minimal exposure’ class. Conclusions: The study’s findings offer an overview of the complex associations between patterns of exposure to PMIEs and associated predictors and outcomes. Clinicians treating HSCWs coping with COVID-19 related stress should be aware of the contribution of exposure to PMIEs to HSCWs’ distress and to the unique constellation of high self-criticism and low self-compassion among HSCWs with exposure to PMIEs. HIGHLIGHTS We examined moral injury among medical staff during COVID-19 pandemic. Three classes were identified: High Exposure (HE), Betrayal-Only (BO), and Minimal Exposure (ME). HE and BO classes reported more psychopathology, low self-compassion and high self-criticism.
Is There One Key Step in the Metastatic Cascade?

Simple Summary To successfully metastasize, cancer cells must complete a sequence of obligatory steps called the metastatic cascade. To model the metastatic cascade, we used the framework of the Drake equation, initially created to describe the emergence of intelligent life in the Milky way, using a similar logic of a sequence of obligatory steps. Then within this framework, we used simulations on breast cancer to investigate the contribution of each step to the metastatic cascade. We show that the half-life of circulating tumor cells is one of the most important parameters in the cascade, suggesting that therapies reducing the survival of those cells in the vascular system could significantly reduce the risk of metastasis. Abstract The majority of cancer-related deaths are the result of metastases (i.e., dissemination and establishment of tumor cells at distant sites from the origin), which develop through a multi-step process classically termed the metastatic cascade. The respective contributions of each step to the metastatic process are well described but are also currently not completely understood. Is there, for example, a critical phase that disproportionately affects the probability of the development of metastases in individual patients? Here, we address this question using a modified Drake equation, initially formulated by the astrophysicist Frank Drake to estimate the probability of the emergence of intelligent civilizations in the Milky Way. Using simulations based on realistic parameter values obtained from the literature for breast cancer, we examine, under the linear progression hypothesis, the contribution of each component of the metastatic cascade. Simulations demonstrate that the most critical parameter governing the formation of clinical metastases is the survival duration of circulating tumor cells (CTCs).
Culturally Adaptive Governance—Building a New Framework for Equity in Aboriginal and Torres Strait Islander Health Research: Theoretical Basis, Ethics, Attributes and Evaluation

Indigenous health inequities persist in Australia due to a system of privilege and racism that has political, economic and social determinants, rather than simply genetic or behavioural causes. Research involving Aboriginal and Torres Strait Islander (‘Indigenous’) communities is routinely funded to understand and address these health inequities, yet current ethical and institutional conventions for Indigenous health research often fall short of community expectations. Typically, mainstream research projects are undertaken using traditional “top-down” approaches to governance that hold inherent tensions with other dominant governance styles and forms. This approach perpetuates long-held power imbalances between those leading the research and those being researched. As an alternative, Indigenous governance focuses on the importance of place, people, relationships and process for addressing power imbalances and achieving equitable outcomes. However, empowering principles of Indigenous governance in mainstream environments is a major challenge for research projects and teams working within organisations that are regulated by Western standards and conventions. This paper outlines the theoretical basis for a new Culturally Adaptive Governance Framework (CAGF) for empowering principles of Indigenous governance as a prerequisite for ethical conduct and practice in Indigenous health research. We suggest new orientations for mainstream research project governance, predicated on translating theoretical and practical attributes of real-world ethics, adaptive governance and critical allyship frameworks to Indigenous health research. The CAGF is being implemented in a national Indigenous multicenter trial evaluating the use of continuous blood glucose monitors as a new technology with the potential to improve diabetes care and treatment for Indigenous Australians—the FlashGM Study. The CAGF is a governance framework that identifies the realities of power, acknowledges the complexities of culture and emerging health technologies, and foregrounds the principle of equity for mainstream Indigenous health research.
APLN/APLNR Signaling Controls Key Pathological Parameters of Glioblastoma

Simple Summary The neurovascular peptide Apelin and its receptor APLNR are upregulated during glioblastoma pathology. Here we summarize their role in the brain tumor microenvironment composed of neurons, astrocytes, and the vascular and immune systems. Targeting APLN/APLNR signaling promises to unfold multimodal actions in future GBM therapy, acting as an anti-angiogenic and an anti-invasive treatment, and offering the possibility to reduce neurological symptoms and increase overall survival simultaneously. Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function. Hence, the delivery of chemotherapeutics into GBM can be compromised. Furthermore, leaky vessels support edema-formation, which can result in severe neurological deficits. The secreted signaling peptide Apelin (APLN) plays an important role in the formation of GBM blood vessels. Both APLN and the Apelin receptor (APLNR) are upregulated in GBM cells and control tumor cell invasiveness. Here we summarize the current evidence on the role of APLN/APLNR signaling during brain tumor pathology. We show that targeting APLN/APLNR can induce anti-angiogenic effects in GBM and simultaneously blunt GBM cell infiltration. In addition, we discuss how manipulation of APLN/APLNR signaling in GBM leads to the normalization of tumor vessels and thereby supports chemotherapy, reduces edema, and improves anti-tumorigenic immune reactions. Hence, therapeutic targeting of APLN/APLNR signaling offers an interesting option to address different pathological hallmarks of GBM.
Molecular Characterization of Carbonic Anhydrase Genes in Lotus japonicus and Their Potential Roles in Symbiotic Nitrogen Fixation

Carbonic anhydrase (CA) plays a vital role in photosynthetic tissues of higher plants, whereas its non-photosynthetic role in the symbiotic root nodule was rarely characterized. In this study, 13 CA genes were identified in the model legume Lotus japonicus by comparison with Arabidopsis CA genes. Using qPCR and promoter-reporter fusion methods, three previously identified nodule-enhanced CA genes (LjαCA2, LjαCA6, and LjβCA1) have been further characterized, which exhibit different spatiotemporal expression patterns during nodule development. LjαCA2 was expressed in the central infection zone of the mature nodule, including both infected and uninfected cells. LjαCA6 was restricted to the vascular bundle of the root and nodule. As for LjβCA1, it was expressed in most cell types of nodule primordia but only in peripheral cortical cells and uninfected cells of the mature nodule. Using CRISPR/Cas9 technology, the knockout of LjβCA1 or both LjαCA2 and its homolog, LjαCA1, did not result in abnormal symbiotic phenotype compared with the wild-type plants, suggesting that LjβCA1 or LjαCA1/2 are not essential for the nitrogen fixation under normal symbiotic conditions. Nevertheless, the nodule-enhanced expression patterns and the diverse distributions in different types of cells imply their potential functions during root nodule symbiosis, such as CO2 fixation, N assimilation, and pH regulation, which await further investigations.
Early-Phase Interventional Trials in Oral Cancer Prevention

Simple Summary Oral cancer is a devastating disease with increasing incidence worldwide. Oral epithelial dysplasia (OED) is a potentially malignant disorder and patients with OED are at increased risk of developing oral cancer. Current strategies for management of OED include surgery or close observation and both fail to address the underlying pathogenesis of the disease. There is an urgent need for evidence-based medical treatments for OED to prevent oral cancer development in this cohort. Chemoprevention trials to date have not delivered therapeutic agents for routine clinical practice. Historically, there has been significant heterogeneity in the design of oral cancer chemoprevention trials, with most failing to selectively recruit patients with biopsy-proven OED, which limits the usefulness of the findings in the OED population. The present paper aims to review the current evidence and the methodology of early-phase trials in oral cancer chemoprevention. Novel strategies in oral cancer chemoprevention will also be discussed. Abstract The increasing breadth of molecular targets, promise of immune-targeted therapies and repurposed agents have heightened interest in cancer prevention. While, to date, testing of oral cancer chemoprevention strategies has failed to deliver therapeutic agents for routine clinical practice, there remains an urgent need for further clinical research to overcome this hurdle. Patients at the greatest risk of disease stand to benefit the most from inclusion in clinical trials; therefore, there is a need to carefully define this population using validated clinical and molecular markers. Safety, tolerability and the efficacy of interventions is assessed through carefully selected endpoints. These endpoints may include pharmacodynamic, clinical, histological and on-target molecular modifications as an individual or as a composite endpoint. Early-phase trials provide an area of opportunity to explore novel and repurposed agents in the setting of oral cancer chemoprevention, eventually leading to phase III trials with clinical endpoints such as transformation and clinical outcome; these studies are large, lengthy and expensive and should be reserved for the most promising of agents. This paper will explore current evidence in oral cancer chemoprevention, drug repurposing, selection of appropriate endpoints for early-phase trials and novel therapeutic angles in oral cancer chemoprevention.
Establishment of a cardiac telehealth program to support cardiovascular diagnosis and care in a remote, resource-poor setting in Uganda

Introduction To address workforce shortages and expand access to care, we developed a telemedicine program incorporating existing infrastructure for delivery of cardiovascular care in Gulu, Northern Uganda. Our study had three objectives: 1) assess feasibility and clinical impact 2) evaluate patient/parent satisfaction and 3) estimate costs. Methods All cardiology clinic visits during a two-year study period were included. All patients received an electrocardiogram and echocardiogram performed by a local nurse in Gulu which were stored and transmitted to the Uganda Heart Institute in the capital of Kampala for remote consultation by a cardiologist. Results were relayed to patients/families following cardiologist interpretation. The following telemedicine process was utilized: 1) clinical intake by nurse in Gulu; 2) ECG and echocardiography acquisition in Gulu; 3) echocardiography transmission to the Uganda Heart Institute in Kampala, Uganda; 4) remote telemedicine consultation by cardiologists in Kampala; and 5) communication of results to patients/families in Gulu. Clinical care and technical aspects were tracked. Diagnoses and recommendations were analyzed by age groups (0–5 years, 6–21 years, 22–50 years and > 50 years). A mixed methods approach involving interviews and surveys was used to assess patient satisfaction. Healthcare sector costs of telemedicine-based cardiovascular care were estimated using time-driven activity-based costing. Results Normal studies made up 47%, 55%, 76% and 45% of 1,324 patients in the four age groups from youngest to oldest. Valvular heart disease (predominantly rheumatic heart disease) was the most common diagnosis in the older three age groups. Medications were prescribed to 31%, 31%, 24%, and 48% of patients in the four age groups. The median time for consultation was 7 days. A thematic analysis of focus group transcripts displayed an overall acceptance and appreciation for telemedicine, citing cost- and time-saving benefits. The cost of telemedicine was $29.48/visit. Conclusions Our data show that transmission and interpretation of echocardiograms from a remote clinic in northern Uganda is feasible, serves a population with a high burden of heart disease, has a significant impact on patient care, is favorably received by patients, and can be delivered at low cost. Further study is needed to better assess the impact relative to existing standards of care and cost effectiveness.
Gender Differences in Psychosocial Outcomes of Hair Loss Resulting from Childhood Irradiation for Tinea Capitis

Recent studies have linked hair loss due to childhood irradiation for tinea capitis, a fungal infection of the scalp, to adverse psychosocial and health outcomes in women. However, no study to date has examined gender differences in the outcomes of this type of hair loss. The current study aimed to investigate gender differences in health and psychosocial outcomes of hair loss resulting from childhood irradiation for tinea capitis, and to identify the risk factors associated with depression in both men and women. Medical records held at the archives of the Israel National Center for Compensation of Scalp Ringworm Victims were retrospectively reviewed for 217 women and 105 men who received maximum disability compensation due to severe hair loss resulting from irradiation for tinea capitis. We found that women were at increased risk of developing psychosocial symptoms, including depression. Gender emerged as a significant predictor of depression, distinct from other predictors, such as marital status, age at radiation, exposure to verbal and physical bullying, low self-esteem, social anxiety, and physical health problems. Thus, the psychosocial needs of patients, particularly female patients, who were irradiated for tinea capitis during childhood need to be taken into account by the healthcare professionals treating them.
Streetlights positively affect the presence of an invasive grass species

Abstract Anthropogenic disturbances associated with urban ecosystems can create favorable conditions for populations of some invasive plant species. Light pollution is one of these disturbances, but how it affects the growth and establishment of invasive plant populations is unknown. Cheatgrass (Bromus tectorum) is a problematic invasive species where it has displaced native grassland communities in the United States, but to our knowledge, there have been no studies of the ecological factors that affect cheatgrass presence in urban ecosystems. We conducted field surveys in urban alleys in Denver, Colorado, to compare the presence of cheatgrass at sites with and without artificial light at night (hereafter artificial light) from streetlights. These streetlights are mounted on utility poles, which cause ground disturbance when installed in alleys; we were able to test the independent effect of poles on cheatgrass establishment because not all poles have streetlights on them. We found that cheatgrass was positively associated with the presence of streetlights and to a lesser extent poles. In addition to cheatgrass, we also found that other plants were positively associated with the presence of both poles and streetlights. Our results suggest that artificial light may benefit the occurrence of cheatgrass and other plant species in urban settings. While invasive populations of cheatgrass in wild habitats attract the most attention from managers, we suggest more consideration for this grass in urban environments where its growth and establishment benefit from anthropogenic changes.