anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis yet to be fully elucidated. Extensive research has highlighted the critical role of gut microbiome in the onset and progression of IgA nephropathy, underscoring its importance in accurately delineating the disease's etiology. For example, gut microbiome dysbacteriosis can lead to the production of nephritogenic IgA1 antibodies, which form immune complexes that deposit in the kidneys, causing inflammation and damage. The gut microbiome, a source of numerous bioactive compounds, interacts with the host and plays a regulatory role in gut-immune axis modulation, earning it the moniker of the "second brain." Recent investigations have particularly emphasized a significant correlation between IgA nephropathy and gut microbiome dysbacteriosis. This article offers a detailed overview of the pathogenic mechanisms of IgA nephropathy, specifically focusing on elucidating how alterations in the gut microbiome are associated with anomalies in the intestinal mucosal system in IgA nephropathy. Additionally, it describes the possible influence of gut microbiome on recurrent IgA nephropathy following kidney transplantation. Furthermore, it compiles potential therapeutic interventions, offering both theoretical and practical foundations for the management of IgA nephropathy. Lastly, the challenges currently faced in the therapeutic approaches to IgA nephropathy are discussed.
INTRODUCTION: Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks.
METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying.
RESULTS: Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05).
DISCUSSION: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.
Myocardial ischemia-reperfusion injury (MIRI) is a widely recognized cardiovascular disease that significantly impacts the prognosis of patients undergoing myocardial infarction recanalization. This condition can be fatal and involves complex pathophysiological mechanisms. Early diagnosis of MIRI is crucial to minimize myocardial damage and reducing mortality. Based on the inherent relationship between platelets and MIRI, we developed biomimetic microbubbles coated with platelet membrane (MB-pla) for early identification of MIRI. The MB-pla were prepared through a recombination process involving platelet membrane obtained from rat whole blood and phospholipids, blended in appropriate proportions. By coating the microbubbles with platelet membrane, MB-pla acquired various adhesion molecules, thereby gaining the capability to selectively adhere to damaged endothelial cells in the context of MIRI. In vitro experiments demonstrated that MB-pla exhibited remarkable targeting characteristics, particularly toward type IV collagen and human umbilical vein endothelial cells that had been injured through hypoxia/reoxygenation procedures. In a rat model of MIRI, the signal intensity produced by MB-pla was notably higher than that of control microbubbles. These findings were consistent with results obtained from fluorescence imaging of isolated hearts and immunofluorescence staining of tissue sections. In conclusion, MB-pla has great potential as a non-invasive early detection method for MIRI. Furthermore, this approach can potentially find application in other conditions involving endothelial injury in the future.
INTRODUCTION: esophageal replacement in children is indicated when it is impossible to maintain the native esophagus, which in the pediatric population includes patients with esophageal atresia and esophageal caustic stenosis. The objective of this communication is to report the experience of a university service with two techniques of esophageal replacement.
METHODS: this is a retrospective study based on the revision of hospital files. The study population consisted of patients who underwent esophageal replacement from 1995 to 2022, at the Hospital de Clínicas of the State University of Campinas. The analyzed data were age, sex, underlying disease, technical aspects, complications, and long-term results.
RESULTS: during the study period, 30 patients underwent esophageal replacement. The most common underlying diseases were esophageal atresia (73.33%) and caustic stenosis (26.67%). Twenty-one patients underwent gastric transposition (70%), and nine underwent esophagocoloplasty (30%). The most frequent postoperative complication was fistula of the proximal anastomosis, which occurred in 14 patients. Most of the patients with fistulas had a spontaneous recovery. There were three deaths. Of the 27 survivors, 24 can feed exclusively by mouth.
CONCLUSION: esophageal replacement in children is a procedure with high morbidity and mortality. Esophagocoloplasty and gastric transposition have similar results and complications, with the exception of proximal anastomotic fistulas, which are generally self-resolving and are more common in esophagocoloplasty. The choice of the best surgical technique must be individualized according to the patients characteristics and the surgeons experience, as both techniques offer the ability to feed orally in the short or medium term.
This is a phase IIa open-label, non-randomized dose-expansion study of OPB-111077 in patients with advanced, treatment refractory cancers who have biopsy-amenable lesions at study entry. Patients on the proposed study will be treated with the RPII dose of OPB-111077 (600mg on a 4 days-on, 3 days-off per week schedule). They will be enrolled in two parallel cohorts: i. patients with tumors predicted to be dependent on oxidative phosphorylation metabolism or oncogene addicted tumors which have developed resistance to primary TKI therapy, or ii. patients with nasopharyngeal carcinoma

Each cohort will contain 11-26 patients, over a period of 12-36 months. Subjects will receive OPB-111077 in 28-day cycles till disease progression or intolerable toxicity. Mandatory tumour biopsies will be performed at baseline and on cycle 1 day 15 (where feasible and accessible). Circulating biomarker blood sampling will be performed on days 1, 11 and 15 of cycle 1, and upon completion of OPB-111077 dosing. Pharmacokinetics blood sampling will be performed on days 11 and 15 of cycle 1. Safety assessments will be performed on cycle 1 day 1, cycle 1 day 8, cycle 1 day 15, bi-weekly till week 8, then monthly thereafter and response assessments will be performed every 8 weeks. Metabolic response assessment by PET/CT will be performed after 2 cycles of treatment, while radiologic response assessment will be performed after every 2 cycles of OPB-111077 from cycle 4 onwards.
###  Posttreatment Exacerbations of Hepatitis

All patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1)]. Discontinuation of anti-HBV therapy, including 3TC and TDF, may be associated with severe acute exacerbations of hepatitis B. Patients infected with HBV who discontinue SYMFI should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

###  Important Differences Among Lamivudine-Containing Products

SYMFI tablets contain a higher dose of the same active ingredient, 3TC, than EPIVIR-HBV® tablets. EPIVIR-HBV was developed for patients with chronic hepatitis B. The formulation and dosage of 3TC in EPIVIR-HBV are not appropriate for patients co-infected with HIV-1 and HBV. Safety and efficacy of 3TC have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV. 

If treatment with EPIVIR-HBV, TDF, or a tenofovir alafenamide (TAF)-containing product is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment.
OBJECTIVE: Chronic hypertension (CHTN) causes vascular damage and resistance in the pregnant person and malperfusion in the placenta which may worsen the endothelial dysfunction of hypertensive disorders of pregnancy (HDP). These conditions frequently co-exist. A cumulative effect has been inconsistently demonstrated in prior studies, and it is unclear how co-existing hypertensive conditions affect pregnancy outcomes. We sought to examine maternal and neonatal outcomes in pregnancies affected by co-existing CHTN and HDP and compare these outcomes to those of pregnancies which were unaffected or affected by either condition alone.
METHODS: This is a retrospective cohort study of singleton deliveries at a single institution 1 October 2013 to 1 October 2021. Data were extracted from the electronic medical record using standardized definitions and billing and diagnosis codes. Pregnant people with no evidence of hypertensive condition were compared to those with CHTN only, HDP only, and co-existing CHTN and HDP. Demographics, baseline clinical data, and use of aspirin or antihypertensive medications were assessed. Maternal outcomes included cesarean delivery, critical range blood pressure, intensive care unit (ICU) admission, and death. Neonatal outcomes included preterm birth <37 weeks' gestation, small for gestational age (SGA) birthweight, ICU admission, and a morbidity composite. Bivariate tests of association were performed using Chi-square test. Crude and adjusted odds ratios (aORs) were calculated using logistic regression for three maternal and four neonatal outcomes. Descriptive statistics and multivariable analyses were performed.
RESULTS: Of 40,840 eligible people, 1451 (3.6%) had CHTN only; 5213 (12.8%) had HDP only; and 1890 (4.6%) had co-existing CHTN and HDP. Though odds of adverse maternal and neonatal outcomes were significantly increased for all hypertensive groups relative to the unaffected referent group, co-existing CHTN and HDP had the highest odds of cesarean delivery (aOR 1.60; 95% confidence interval (CI) 1.45-1.77), critical blood pressure (OR 41.54; 95% CI 35.96-47.99), maternal ICU admission or death (aOR 3.52; 95% CI 2.65-4.67), preterm birth (aOR 2.76; 95% CI 2.41-3.16), and SGA birthweight (aOR 1.61; 95% CI 1.39-1.87).
CONCLUSIONS: Hypertensive disorders of pregnancy in the setting of CHTN are associated with the highest odds of serious consequences on the pregnant person and neonate independent of maternal comorbidities and prematurity. Antihypertensive medication use lowers the odds of some adverse outcomes. Patients should be informed of heightened risks, but optimal management remains unclear.
BACKGROUND: Sepsis is a common critical condition seen in clinical settings, with mitochondrial dysfunction playing an important role in the progression of sepsis. However, a mitochondrial prognosis model related to sepsis has not been established yet, and the relationship between the sepsis immune microenvironment and mitochondria remains unclear.
METHODS: Sepsis prognostic mitochondria-associated genes (MiAGs) were screened by univariate Cox, multivariate Cox, and LASSO analysis from the GEO dataset. Consensus Cluster was used to analyze MiAGs-based molecular subtypes for sepsis. The ESTIMATE and ssGSEA algorithms were used to analyze the situation of sepsis immune cell infiltration and its relation to MiAGs. Further, MiAGs score was calculated to construct a sepsis prognosis risk model to predict the prognosis of sepsis patients. Clinical blood samples were used to investigate the expression level of selected MiAGs in sepsis. Single-cell sequencing analysis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and ATP detection were used to verify the influence of MiAGs on mitochondrial dysfunction in sepsis.
RESULTS: A total of 5 MiAGs of sepsis were screened. Based on MiAGs, sepsis MiAGs subtypes were analyzed, where Cluster A had a better prognosis than Cluster B, and there were significant differences in immune infiltration between the two clusters. The sepsis mitochondrial prognosis model suggested that the high MiAG score group had a shorter survival time compared to the low MiAG score group. Significant differences were also observed in the immune microenvironment between the high and low MiAG score groups. Prognostic analysis and the Nomogram indicated that the MiAG score is an independent prognostic factor in sepsis. Single-cell sequencing analysis exhibited the possible influence of MiAGs on the mitochondrial function of monocytes. Finally, the downregulation of the COX7B could effectively improve mitochondrial function in the LPS-stimulated sepsis model.
CONCLUSION: Our findings suggest that MiAGs can be used to predict the prognosis of sepsis and that regulating the mitochondrial prognostic gene COX7B can effectively improve the mitochondrial function of immune cells in sepsis.
As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has emerged as a major cause of noninfectious mortality in laying hens, resulting in substantial economic losses to the poultry industry. This study aimed to investigate the therapeutic effects of magnolol on FLHS in postpeak laying hen model, focusing on lipid metabolism, antioxidative capacity, and potential molecular mechanisms of action. We selected 150 Xinhua laying hens aged 50 wk and divided them into normal diet group (ND), high-fat diet group (HFD), 100 mg/kg magnolol group (MG100), 300 mg/kg magnolol group (MG300), 500 mg/kg magnolol group (MG500) on average. The experiment lasted for 6 wk, and liver samples were collected from the hens at the end of the experiment. The results demonstrated that the inclusion of magnolol in the diet had a significant impact on various factors. It led to a reduction in weight, an increase in egg production rate, a decrease in blood lipid levels, and an improvement in abnormal liver function, liver steatosis, and oxidative stress. These effects were particularly prominent in the MG500 group. The RNA-Seq analysis demonstrated that in the MG500 group, there was a down-regulation of genes associated with fatty acid synthesis (Acc, Fasn, Scd, Srebf1, Elovl6) compared to the HFD group. Moreover, genes related to fatty acid oxidation (CPT1A and PGC1α) were found to be up-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these differentially expressed genes indicated their enrichment in the PPAR signaling pathway. These findings demonstrate that magnolol can mitigate FLHS by inhibiting fatty acid synthesis and promoting fatty acid oxidation. This discovery offers a novel approach for treating FLHS in laying hens, reducing the economic losses associate with FLHS.
The efficacy of combination therapy with an immune checkpoint inhibitor (ICI) and cytotoxic chemotherapeutic agents has been investigated in cancer, including melanoma. Before ICIs were introduced, dacarbazine or temozolomide (TMZ) were used to treat melanoma. Several studies using glioma or colorectal cancer cells showed that TMZ can increase the tumor mutation burden (TMB) and induce mismatch repair (MMR) deficiency associated with microsatellite instability (MSI). These could increase immunoreactivity to an ICI, but this has not been evaluated in melanoma cells. We investigated the effects of TMZ on MSI status and TMB in melanoma cells. To evaluate the TMB, we performed whole-exome sequencing using genomic DNA from the human melanoma cell lines Mel18, A375, WM266-4, G361, and TXM18 before and after TMZ treatment. Polymerase chain reaction amplification of five mononucleotide repeat markers, BAT25, BAT26, NR21, NR24, and MONO27, was performed, and we analyzed changes in the MSI status. In all cell lines, the TMB was increased after TMZ treatment (the change amount of TMB with ≤ 5% variant allele frequency [VAF] was 18.0-38.3 mutations per megabase) even in the condition without obvious cytological damage. MSI after TMZ treatment was not observed in any cells. TMZ increased TMB but did not change MSI status in melanoma cells.
Natural non-psychoactive cannabinoids such as cannabigerol (CBG), cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN) are increasingly consumed as constituents of dietary products because of the health benefits claims. Cannabinoids may reduce certain types of pain, nausea, and anxiety. Anti-inflammatory and even anti-carcinogenic properties have been discussed. However, there are insufficient data available regarding their potential (geno-)toxic effects. Therefore, we tested CBG, CBD, CBC, CBDV, and CBN for their genotoxic potential and effects on mitosis and cell cycle in human lymphoblastoid TK6 cells. The selected cannabinoids (except CBDV) induced increased micronuclei formation, which was reduced with the addition of a metabolic activation system (S9 mix). CBDV induced micronuclei only after metabolic activation. Mitotic disturbances were observed with all tested cannabinoids, while G1 phase accumulation of cells was observed for CBG, CBD and CBDV. The genotoxic effects occurred at about 1000-fold higher concentrations than are reported as blood levels from human consumption. However, the results clearly indicate a need for further research into the genotoxic effects of cannabinoids. The mechanism of the mitotic disturbance, the shape of the dose-response curves and the possible effects of mixtures of cannabinoids are aspects which need clarification.
The protocol is designed to first evaluate the accuracy of supine vs. non-supine detection in 15 subjects (hereafter referred to as study 1). In study 2, patients who had completed a baseline polysomnography (PSG) with a minimum of four hours of sleep time were to wear the Night Shift for two nights without feedback to confirm their willingness to continue with the study, followed by 28 nights of vibro-tactile position therapy. A follow-up PSG was to be conducted as soon as possible to the completion of the 28-nights of treatment. During enrollment subjects were to complete pre-treatment questionnaires designed to measure daytime sleepiness, insomnia severity, depression, anxiety, and quality of life. The same instruments were completed post-treatment on the morning after the 28th night of treatment. Subjects completed daily logs to confirm device utilization and identify potential non-device related factors that could influence study completion.
Participants will receive macitentan as a monotherapy or add-on to an existing therapy daily for 24 weeks during core treatment period. Optional treatment extension period of up to 1 year for those participants who completed the core treatment period.
Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.