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Journal of Medical Internet Research May 2024Mobile health (mHealth) uses mobile technologies to promote wellness and help disease management. Although mHealth solutions used in the clinical setting have typically... (Review)
Review
BACKGROUND
Mobile health (mHealth) uses mobile technologies to promote wellness and help disease management. Although mHealth solutions used in the clinical setting have typically been medical-grade devices, passive and active sensing capabilities of consumer-grade devices like smartphones and activity trackers have the potential to bridge information gaps regarding patients' behaviors, environment, lifestyle, and other ubiquitous data. Individuals are increasingly adopting mHealth solutions, which facilitate the collection of patient-generated health data (PGHD). Health care professionals (HCPs) could potentially use these data to support care of chronic conditions. However, there is limited research on real-life experiences of HPCs using PGHD from consumer-grade mHealth solutions in the clinical context.
OBJECTIVE
This systematic review aims to analyze existing literature to identify how HCPs have used PGHD from consumer-grade mobile devices in the clinical setting. The objectives are to determine the types of PGHD used by HCPs, in which health conditions they use them, and to understand the motivations behind their willingness to use them.
METHODS
A systematic literature review was the main research method to synthesize prior research. Eligible studies were identified through comprehensive searches in health, biomedicine, and computer science databases, and a complementary hand search was performed. The search strategy was constructed iteratively based on key topics related to PGHD, HCPs, and mobile technologies. The screening process involved 2 stages. Data extraction was performed using a predefined form. The extracted data were summarized using a combination of descriptive and narrative syntheses.
RESULTS
The review included 16 studies. The studies spanned from 2015 to 2021, with a majority published in 2019 or later. Studies showed that HCPs have been reviewing PGHD through various channels, including solutions portals and patients' devices. PGHD about patients' behavior seem particularly useful for HCPs. Our findings suggest that PGHD are more commonly used by HCPs to treat conditions related to lifestyle, such as diabetes and obesity. Physicians were the most frequently reported users of PGHD, participating in more than 80% of the studies.
CONCLUSIONS
PGHD collection through mHealth solutions has proven beneficial for patients and can also support HCPs. PGHD have been particularly useful to treat conditions related to lifestyle, such as diabetes, cardiovascular diseases, and obesity, or in domains with high levels of uncertainty, such as infertility. Integrating PGHD into clinical care poses challenges related to privacy and accessibility. Some HCPs have identified that though PGHD from consumer devices might not be perfect or completely accurate, their perceived clinical value outweighs the alternative of having no data. Despite their perceived value, our findings reveal their use in clinical practice is still scarce.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
RR2-10.2196/39389.
Topics: Humans; Telemedicine; Health Personnel; Patient Generated Health Data; Smartphone
PubMed: 38820580
DOI: 10.2196/49320 -
Frontiers in Medicine 2024Psoriasis is a chronic inflammatory skin disease. EDP1815 is an oral, gut-restricted preparation of non-live , the first of a new immunomodulatory therapeutic class...
BACKGROUND
Psoriasis is a chronic inflammatory skin disease. EDP1815 is an oral, gut-restricted preparation of non-live , the first of a new immunomodulatory therapeutic class targeting the small intestine to generate systemic anti-inflammatory responses.
OBJECTIVE
To evaluate safety and efficacy of EDP1815 in mild-to-moderate psoriasis in a proof-of-concept study.
METHODS
A phase 2, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study with a 16-week treatment period and up to 24 weeks of follow-up. Participants were randomized to receive 1, 4, or 10 capsules daily.
RESULTS
EDP1815 was well tolerated with comparable rates of treatment-emergent adverse events to placebo, and no drug-related serious adverse events. Clinically meaningful responses to EDP1815, defined as at least 50% reduction in Psoriasis Area and Severity Index (PASI-50) at week 16, were observed in all 3 cohorts, statistically significant in the 1-capsule (29.7%; = 0.048) and 4-capsule (31.9%; = 0.022) groups, compared with placebo (12.1%). Among EDP1815-treated PASI-50 responders at week 16, 60% (18/30) maintained or improved off-treatment responses at week 40.
LIMITATIONS
Continued off-treatment improvement past 16 weeks shows potential for greater therapeutic benefit that was not assessed.
CONCLUSION
EDP1815 was well-tolerated with a placebo-like safety profile, and had meaningful efficacy outcomes in psoriasis, validating this novel immunomodulatory approach.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov/search?term=NCT04603027, identifier NCT04603027.
PubMed: 38813388
DOI: 10.3389/fmed.2024.1292406 -
Frontiers in Neuroscience 2024Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have... (Review)
Review
Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.
PubMed: 38812976
DOI: 10.3389/fnins.2024.1386866 -
Frontiers in Bioscience (Landmark... May 2024Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes... (Review)
Review
Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.
Topics: Humans; Choline; Non-alcoholic Fatty Liver Disease; Animals; Gastrointestinal Microbiome; Neoplasms; Liver Neoplasms; Lipid Metabolism
PubMed: 38812309
DOI: 10.31083/j.fbl2905182 -
Molecular Cancer May 2024Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription...
BACKGROUND
Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.
METHODS
We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.
RESULTS
Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.
CONCLUSIONS
Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes.
Topics: Male; Prostatic Neoplasms; Animals; Mice; Humans; PTEN Phosphohydrolase; Disease Progression; Tumor Microenvironment; Senescence-Associated Secretory Phenotype; Proto-Oncogene Proteins c-jun; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Gene Expression Profiling; Cellular Senescence; Disease Models, Animal
PubMed: 38811984
DOI: 10.1186/s12943-024-02022-x -
Scientific Reports May 2024Cryopreservation of sperm can cause oxidative stress and damage, leading to decreased different functional parameters and fertilization potential. In this study, we...
Cryopreservation of sperm can cause oxidative stress and damage, leading to decreased different functional parameters and fertilization potential. In this study, we evaluated two types of HS donors: NaHS, a fast-releasing donor, and GYY4137, a slow-releasing donor during cryopreservation of goat sperm. Initially, we determined that 1.5 and 3 μM NaHS, and 15 and 30 μM GYY4137 are optimal concentrations that improved different sperm functional parameters including motility, viability, membrane integrity, lipid peroxidation, and ROS production during incubation at 38.5 °C for 90 min. We subsequently evaluated the impact of the optimal concentration of NaHS and GYY4137 supplementation on various functional parameters following thawing during cryopreservation. Our data revealed that supplementation of extender improved different parameters including post-thaw sperm motility, viability, membrane integrity, and reduced DNA damage compared to the frozen-thawed control group. The supplementation also restored the redox state, decreased lipid peroxidation, and improved mitochondrial membrane potential in the thawed sperm. Finally, we found that supplementation of the extender with NaHS and GYY4137 enhanced IVF outcomes in terms of blastocyst rate and quality of blastocysts. Our results suggest that both donors can be applied for cryopreservation as antioxidants to improve sperm quality and IVF outcomes of frozen-thawed goat sperm.
Topics: Male; Cryopreservation; Animals; Oxidative Stress; Fertilization in Vitro; Spermatozoa; Goats; Sperm Motility; Semen Preservation; Organothiophosphorus Compounds; Lipid Peroxidation; Hydrogen Sulfide; Cryoprotective Agents; Cell Survival; Female; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Semen Analysis; Morpholines; Sulfides
PubMed: 38811647
DOI: 10.1038/s41598-024-62485-2 -
Scientific Reports May 2024The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial...
The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.
Topics: Humans; Aripiprazole; COVID-19; Male; Female; Antipsychotic Agents; Middle Aged; Retrospective Studies; Aged; SARS-CoV-2; COVID-19 Drug Treatment; Adult; Aged, 80 and over
PubMed: 38811612
DOI: 10.1038/s41598-024-60297-y -
NPJ Systems Biology and Applications May 2024The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict...
The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.
Topics: Humans; Forkhead Transcription Factors; T-Lymphocytes, Regulatory; Transcriptome; Computational Biology; Gene Expression Regulation; Gene Expression Profiling; Genes, Regulator
PubMed: 38811598
DOI: 10.1038/s41540-024-00387-9 -
PLoS Computational Biology May 2024Machine learning (ML) is increasingly being used to guide biological discovery in biomedicine such as prioritizing promising small molecules in drug discovery. In those...
Machine learning (ML) is increasingly being used to guide biological discovery in biomedicine such as prioritizing promising small molecules in drug discovery. In those applications, ML models are used to predict the properties of biological systems, and researchers use these predictions to prioritize candidates as new biological hypotheses for downstream experimental validations. However, when applied to unseen situations, these models can be overconfident and produce a large number of false positives. One solution to address this issue is to quantify the model's prediction uncertainty and provide a set of hypotheses with a controlled false discovery rate (FDR) pre-specified by researchers. We propose CPEC, an ML framework for FDR-controlled biological discovery. We demonstrate its effectiveness using enzyme function annotation as a case study, simulating the discovery process of identifying the functions of less-characterized enzymes. CPEC integrates a deep learning model with a statistical tool known as conformal prediction, providing accurate and FDR-controlled function predictions for a given protein enzyme. Conformal prediction provides rigorous statistical guarantees to the predictive model and ensures that the expected FDR will not exceed a user-specified level with high probability. Evaluation experiments show that CPEC achieves reliable FDR control, better or comparable prediction performance at a lower FDR than existing methods, and accurate predictions for enzymes under-represented in the training data. We expect CPEC to be a useful tool for biological discovery applications where a high yield rate in validation experiments is desired but the experimental budget is limited.
PubMed: 38809942
DOI: 10.1371/journal.pcbi.1012135 -
Asian Pacific Journal of Cancer... May 2024Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited...
OBJECTIVE
Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited efficacy in prolonging survival rates. This study aimed to assess the anticancer properties of Aaptos suberitoides extracts and fraction on the U87 cell line, serving as a representative model for GBM.
METHODS
U87 cells were treated with ethanol extracts derived from Aaptos suberitoides, specifically two extracts (OAA-1 and OAA-2) and one ethyl acetate fraction (EA) isolated from specimens collected on Pramuka Island and Tinjil Island. The evaluation encompased microscopic observation and MTT assay to determine the IC50. Subsequently, antiproliferative effects were investigated through apoptosis and cell cycle assays.
RESULTS
The extract demonstrated cytotoxic activity against U87 cells, with OAA-1 and OAA-2 exhibiting IC50 values of 35.78 μg/mL and 25.38 μg/mL, respectively. OAA-1 notably induced apoptosis at 50 μg/mL and induced cell cycle arrest. On other hand, OAA-2, while also inducing apoptosis significantly, had a lesser impact on cell cycle arrest. In contrast, EA induced significant apoptosis at a concentration of 100 μg/mL.
CONCLUSION
The ethanol extracts and the ethyl acetate fraction of Aaptos suberitoides emerged as a promising candidate for Glioblastoma Multiforme cancer therapy, showing potential in inhibiting cell proliferation and inducing apoptosis.
Topics: Humans; Glioblastoma; Apoptosis; Cell Proliferation; Plant Extracts; Tumor Cells, Cultured; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Brain Neoplasms
PubMed: 38809654
DOI: 10.31557/APJCP.2024.25.5.1815