anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE: A tumor antigen protein or gene of polo - like kinase 1 is provided to be function as tumor antigen which can be recognized by cytotoxic T lymphocyte. CONSTITUTION: A tumor antigen protein or gene of polo - like kinase 1 is recognized by cytotoxic T lymphocyte by combining with MHC classIantigen or II antigen. The tumor antigen protein or gene of polo - like kinase 1 includes the polo-like kinase 1 induced sequence number 1 and a derivative having the protein consisting of the amino acid sequence described in the sequence number 3 or a derivative having the functionally identical property as the protein. The polo - like kinase 1 is mouse or human origin. The protein consisting of the amino acid sequence of the sequence number 1 is coded from the gene consisting of the base sequence described in the sequence number 2. The protein consisting of the amino acid sequence described in the sequence number 3 is coded from the gene consisting of the base sequence described in the sequence number 4.
Approximately 42 million adults are living with HIV/AIDS. The predominant mode of HIV transmission worldwide is through heterosexual contact. While many behavioral and biologic factors are associated with sexual transmission of HIV, viral load has been identified as the chief predictor of the risk of sexual transmission. Research has shown a strong correlation between blood plasma viral load and genital tract viral load. Antiretroviral medications can reduce blood plasma and genital tract HIV RNA levels, but antiretrovirals also lead to drug resistant HIV. In the United States and Europe, 2% to 27% of newly infected patients are infected with drug resistant HIV. There are reports of resistant genotypic variants in the genital tract that differ from variants found in the blood.

Understanding the dynamics of HIV in the genital tract is of great importance in strategies to control transmission of HIV. This study will evaluate the levels and variants of HIV in the blood and genital tracts of women taking antiretroviral medication.

Both women who are failing their current antiretroviral regimen (Group 1) and those who are fully suppressed on antiretroviral therapy (Group 2) will be enrolled in this study. Women in Group 1 will have study visits at study entry, 2 weeks after changing medications, then every 4 weeks until the amount of HIV in the blood and genital tract are undetectable. Drug levels in the blood and genital tract will also be measured at the first visit and after changing medications. Once the level of HIV is undetectable, women will be seen every 3 months for 36 months. Women in Group 1 will be followed no more than 42 months. Women in Group 2 will have study visits for blood and genital tract collections at study entry and then every 4 weeks for 12 months.
UNLABELLED: Nontyphoidal Salmonella (NTS) is a predominant cause of invasive disease in sub-Saharan Africa especially among children under 5 years. Asymptomatic fecal shedding of NTS is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings. However, the role of pathogen shedding in invasive disease is unknown. This study aimed to investigate the prevalence and duration of fecal shedding of NTS among children under 5 years convalescing from invasive NTS disease and among healthy individuals in the community. Children presenting with fever of ≥38°C with or without diarrhea were recruited at four health facilities in Nairobi, between June 2021 and August 2023. Blood and stool samples collected were subjected to culture for the isolation of NTS (S. Enteritidis and S. Typhimurium). Children with NTS culture-positive samples (index cases) were followed up post-acute disease where household contacts and controls provided stool samples for isolation of NTS. NTS prevalence among the 3,293 individuals recruited was 1.52%. Asymptomatic shedding post-treatment was observed in almost one-third (31%) of the 42 index cases followed up. Of the 13 with intestinal shedding, 7 were shedding NTS of the same sequence type (ST) as the one recovered during acute disease. The longest duration of intestinal shedding was 3 months post-treatment. Of the 241 healthy individuals recruited, 8 had asymptomatic shedding of NTS, and 2 of these were closely related to those recovered from index cases. These findings support the hypothesis of human-to-human transmission of NTS in sub-Saharan Africa highlighting the possible benefit of vaccine introduction.
IMPORTANCE: Asymptomatic fecal shedding of nontyphoidal Salmonella (NTS) is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings which could lead to invasive disease among high-risk populations, especially children. Our findings reiterate the hypothesis that human reservoirs could be important in the transmission of nontyphoidal Salmonella in sub-Saharan Africa. This underscores the importance of developing infection prevention measures which could include vaccine deployment and improving water, sanitation and hygiene infrastructure.
INTRODUCTION: This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs.
METHODS: Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE.
RESULTS: We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m6A-SNPs and m7G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 and IRF7. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, HLA-DQB1, HLA-DRB1 and IRF7 exhibited abnormalities in CD8+ T cells, IRF7 displayed abnormal expression in CD4+ T cells, while HLA-DRB1 and IRF7 were also distinctly perturbed in natural killer cells.
DISCUSSION: This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Participation will last approximately 4-6 months. Participants will be encouraged to attend Pickleball sessions at the YMCA at least twice a week. Each session will last 2 hours, and participants will be encouraged to attend at least one hour. Participants will receive a Fitbit to wear continuously 24/7 over 4-6 months to track steps and activity intensity. Participants will also be asked to wear an electronic device (accelerometer) over their right hip during specific time points throughout the study to better understand how pickleball participation contributes to physical activity levels.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software-assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS- M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.
Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Recent Advances: Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation. For this reason, there is a growing interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, which requires the accurate knowledge of the cell context and the specific time frame both of NRF2 activation and inhibition. This appears to be an important prerequisite and reflects the extreme complexity of the NRF2 signaling, characterized by an intrinsic dualism that mediates beneficial or detrimental effects even in the same biological process. Critical Issues: Of crucial importance will be to understand whether the NRF2 activity modulation might be exploited to exert beneficial outcomes in patients suffering from pathological conditions, in which the OS and the deregulation of inflammatory processes play a crucial role. Future Directions: In this review, we discuss the dual involvement of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and carcinogenesis and we present an overview of the most recent therapeutic modulators of NRF2, particularly emphasizing on those selected for clinical trials. Antioxid. Redox Signal. 40, 636-662.
Recent efforts to reclassify non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are intended to divert attention to the metabolic basis of the disease rather than to alcohol consumption. This reclassification recognizes the role of obesity, sedentary lifestyles and poor dietary habits in the development of the disease, leading to a better understanding of its etiology. Nevertheless, the transition has posed its own challenges, particularly with regard to communication between patient and healthcare professional. Many healthcare professionals report difficulty in explaining the nuanced concepts, especially the term "steatosis". In addition, the change in terminology has not yet removed the stigma, with ongoing debates about the appropriateness of the terms "fatty" and "steatotic". Surveys suggest that while "obesity" may be perceived as more stigmatizing, the medical term "steatotic liver disease" is not considered as stigmatizing, indicating a disconnect in perceptions between healthcare professionals and patients.
PURPOSE: In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases.
METHODS: We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis.
RESULTS: There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis.
CONCLUSION: However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.
The present invention provides a method for detection of at least one allele of a genetic locus and can be used to provide direct determination of the haplotype. The method comprises amplifying genomic DNA with a primer pair that spans an intron sequence and defines a DNA sequence in genetic linkage with an allele to be detected. The primer-­defined DNA sequence contains a sufficient number of intron sequence nucleotides to characterize the allele. Genomic DNA is amplified to produce an amplified DNA sequence characteristic of the allele. The amplified DNA sequence is analyzed to detect the presence of a genetic variation in the amplified DNA sequence such as a change in the length of the sequence, gain or loss of a restriction site or substitution of a nucleotide. The variation is characteristic of the allele to be detected and can be used to detect remove alleles. Kits comprising one or more of the reagents used in the method are also described.
BACKGROUND AND PURPOSE: GRIN-related disorders are neurodevelopmental disorders caused by mutations in N-methyl-D-aspartate receptor (NMDAR) subunit genes. A large fraction of these mutations lead to a 'gain of function' (GoF) of the NMDAR. Patients present with a range of symptoms including epilepsy, intellectual disability, behavioural and motor. Controlling seizures is a significant unmet medical need in most patients with GRIN-related disorders. Although several hundred GRIN mutations have been identified in humans, until recently none of the mouse models carrying Grin mutations/deletions showed an epileptic phenotype. The two recent exceptions both carry mutations of GluN2A. The aim of this study was to assess the efficacy of radiprodil, a selective negative allosteric modulator of GluN2B-containing NMDARs, in counteracting audiogenic seizures (AGS) in a murine model carrying the GluN2A(N615S) homozygous mutation (Grin2aS/S mice).
EXPERIMENTAL APPROACH: Grin2aS/S mice were acutely treated with radiprodil at different doses before the presentation of a high-frequency acoustic stimulus commonly used for AGS induction.
KEY RESULTS: Radiprodil significantly and dose-dependently reduced the onset and severity of AGS in Grin2aS/S mice. Surprisingly, the results revealed a sex-dependent difference in AGS susceptibility and in the dose-dependent protection of radiprodil in the two genders. Specifically, radiprodil was more effective in female versus male mice.
CONCLUSION AND IMPLICATIONS: Overall, our data clearly show that radiprodil, a GluN2B selective negative allosteric modulator, may have the potential to control seizures in patients with GRIN2A GoF mutations. Further studies are warranted to better understand the sex-dependent effects observed in this study.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates. We have previously carried out whole genome sequencing of HPV+ HNSCC tumors that failed concurrent cisplatin and radiation treatment and discovered that MACROD2 deletion is enriched among these tumors. In the current study, we sought to investigate the mechanistic role of MACROD2 in HPV+ HNSCC treatment resistance. Our results indicate that MACROD2 depletion in HNSCC cell lines leads to increased cell viability and colony formation capacity. Interestingly, MACROD2 depletion did not alter cisplatin sensitivity but led to an increase in radiation resistance of HPV+ HNSCC cell lines. RNA sequencing and immunofluorescence microscopy demonstrated that MACROD2-depleted HPV+ HNSCC cells displayed elevated levels of hypoxia and an altered DNA damage response. Taken together, this study establishes and characterizes the role of MACROD2 in HPV+ HNSCC radioresistance. Further work is needed to validate MACROD2 as a biomarker of treatment failure and to understand how to overcome the identified molecular mechanisms of resistance.
The invention belongs to the technical field of preparation of pharmaceutical preparations, and particularly relates to an oseltamivir phosphate sustained-release suspension and a preparation method thereof. The invention utilizes the emulsion solvent coating technology and adopts a solvent volatilization method to prepare the oseltamivir resin microcapsule; and uniformly dispersing the oseltamivir resin microcapsules in the suspension matrix to obtain the oseltamivir phosphate sustained-release suspension. The preparation method has simple process and lower cost, and is easy for industrial production; the emulsion coating can slowly release the medicine, reduce the irritation to stomach, prolong the action time of the medicine and reduce the administration times of patients. Compared with the common quick-release preparation, the sustained-release preparation of the invention is convenient to carry and can reduce the taking times. Is more suitable for children and dysphagia patients, and can improve the medication compliance of patients. Meanwhile, the medicine hardly undergoes ion exchange in the oral cavity, and the bitter taste of the medicine can be effectively masked.
DUOPA may increase the risk for elevated (above the upper limit of normal for the reference range) blood urea nitrogen (BUN) and creatine phosphokinase (CPK). In the controlled clinical trial, the shift from a low or normal value at baseline to an increased BUN value was greater for DUOPA-treated patients (13%) than for patients treated with oral immediate-release carbidopa-levodopa (4%). The shift from a low or normal value at baseline to an increased CPK value was greater for DUOPA-treated patients (17%) than for patients treated with oral immediate-release carbidopa-levodopa (7%). The incidence of patients with a markedly increased BUN (≥10 mmol/L; ≥28 mg/dL) was greater for patients treated with DUOPA (11%) than that for patients treated with oral immediate-release carbidopa-levodopa (0%). The incidence of patients with an increased CPK (>3 times the upper limit of normal) was greater for patients treated with DUOPA (9%) than that for patients treated with oral immediate-release carbidopa-levodopa (0%). 

Patients taking levodopa or carbidopa-levodopa may have increased levels of catecholamines and their metabolites in plasma and urine giving false positive results suggesting the diagnosis of pheochromocytoma in patients on levodopa and carbidopa-levodopa.
While the standard treatment approaches of the hospital are applied to all patients, a nursing navigation program will be applied in addition to the patients in the experimental group. The navigation program will be started on the first day of radiotherapy by giving a 30-minute visual training and handbook related to expected side effects. Afterwards, patient follow-up will continue with phone reminders and weekly follow-up for seven weeks.
Patients with heart failure (HF) reported poor quality of life (QOL) due to different reasons among which fatigue is the most important. Improving QOL is a crucial objective for patients with HF and their primary health care providers. Managing fatigue with medication is not enough. Benson's relaxation technique (BRT) is a complementary therapy used to manage fatigue among different populations with limited studies checking its effect among patients diagnosed with HF. The purpose of this quasi-experimental study was to check the effect of BRT on fatigue and QOL among 140 (68 intervention and 72 control) patients diagnosed with HF. Intervention group performed BRT for 20 minutes twice a day for 2 months. Control group received regular care from their health care providers. At baseline, there were no differences between intervention and control groups regarding fatigue, physical component summary, and mental component summary. At follow-up, intervention group had higher scores in physical and mental component summaries than control group (45.48 ± 10.52 vs 37.97 ± 14.78) and (46.22 ± 8.39 vs 41.01 ± 10.36), respectively. Also, intervention group had lower levels of fatigue than control group (2.54 ± 0.87 vs 6.33 ± 0.61). In conclusion, the use of BRT as a complementary therapy for patients with HF might decrease fatigue level and improve QOL.
The citrate, tartrate, malate and ascorbate of S-adenosyl L-methionine (S.A.M) are new. A yeast contg. SAM undergoes lysis and the SAM is fixed onto a cationic exchange resin. It is then eluted with the desired organic acid and the salt is pptd. by addn. of an organic solvent. The yeast is pref. enriched saccharomyces cerevisiae or torulopsis. The lysis is effected chemically, using a mineral or organic acid, ultrasonically, or by autolysis. The salts are used in the treatment of heptatic insufficiency denutrition, convalescence, post-infectious states, atheromanoses, anaemia, Parkisons disease, and correction of secondary effects caused by treatment with L-DOPA.