anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1A946T) and confers an increased risk for several autoimmune diseases, including T1D. We hypothesized that the IFIH1A946T risk variant, (IFIH1R) would promote T1D pathogenesis by stimulating type I interferon (IFN I) signaling leading to immune cell alterations. To test this, we developed Ifih1R knock-in mice on the non-obese diabetic (NOD) mouse background, a spontaneous T1D model. Our results revealed a modest increase in diabetes incidence and insulitis in Ifih1R compared to non-risk Ifih1 (Ifih1NR) mice and a significant acceleration of diabetes onset in Ifih1R females. Ifih1R mice exhibited a significantly enhanced interferon stimulated gene (ISG) signature compared to Ifih1NR, indicative of increased IFN I signaling. Ifih1R mice exhibited an increased frequency of plasma cells as well as tissue-dependent changes in the frequency and activation of CD8+ T cells. Our results indicate that IFIH1R may contribute to T1D pathogenesis by altering the frequency and activation of immune cells. These findings advance our knowledge on the connection between the rs1990760 variant and T1D. Further, these data are the first to demonstrate effects of Ifih1R in NOD mice, which will be important to consider for the development of therapeutics for T1D.
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy was discontinued in intrapartum.
All patients will be treated with a LPD containing 0.6g protein/kg BW per day and 120-125 kJ/kg BW per day.The patients will be followed-up for one year. The patients will come to the hospital every 4 weeks.
The investigators will collect 165 acute stroke patients who suffer from stroke within one month and have potential of rehabilitation. The participants will be divided into mild, moderate and severe groups according to Modified Rankin Scale (MRS). The patients are admitted for 6 weeks or extend to 12 weeks if necessary after evaluation. Comprehensive rehabilitation programs including Physical Therapy (PT), Occupational Therapy (OT) or Speech Therapy (ST) will be done for two hour each every day and 5 days per week for 6-12 weeks. Initial assessment will be done within 3 days and the following assessment will be done 6 weeks or 12 weeks after rehabilitation intervention by physician and well-trained therapists. We collect basic data including sex, age, etiology of stroke, affected side, premorbid functional condition, onset time, initial function on admission, Brunnstrom stage, Charlson Comorbidity Scoring and intensity of rehabilitation. Functional assessment including: Modified Rankin Scale (MRS); Barthel Index; swallowing and feeding function, Mini Nutrition Assessment; Euro QoL-5D; Lawton-Brody IADL Scale; Berg Balance Scale (BBS); Gait speed; 6 minutes walking test; Revised Nottingham sensory assessment(RNSA); Mini-mental state examination (MMSE); Motor Activity Log(MAL); Canadian Occupational Performance Measurement(COPM); aphasia evaluation. Data analysis will be done by two-way ANOVA, paired t test, regression and multiple variant analysis.
This study aims to determine to what extent the hyperinsulinemia commonly associated with insulin resistance (IR) in those at risk for type 2 diabetes (T2D) is a primary phenomenon, rather than merely a secondary, compensatory response to IR. The hypothesis is that some people with obesity and hyperinsulinemia exhibit a primary, non-compensatory hyperinsulinemia that may foment IR and its dysmetabolic sequelae. If this were the case, lowering insulin levels should not result in a proportional rise in blood glucose as might be expected if the hyperinsulinemia truly were purely compensatory. This hypothesis has been difficult to prove, however, because of the tight feedback mechanism between blood glucose and insulin secretion; under normal circumstances insulin secretion declines only alongside blood glucose. As such, an attempt to lower insulin levels independently of blood glucose will raise blood glucose and trigger further insulin secretion, negating the purpose of the experiment. In order to circumvent this feedback regulation of glucose-stimulated insulin secretion, this study will adapt the existing insulin suppression test (IST) technique, which employs the somatostatin receptor ligand octreotide to suppress endogenous insulin secretion and then replaces insulin and dextrose exogenously as a measure of insulin action. In addition to employing the current standard hyperinsulinemic IST protocol to assess insulin sensitivity, this study will introduce a preceding, euinsulinemic step, in which insulin is lowered toward a healthy fasting serum insulin while assessing the resultant steady-state glucose. The primary endpoints in this study are the steady-state plasma glucose and serum insulin levels during low- and high-dose insulin infusions meant to induce euinsulinemia and hyperinsulinemia, respectively. The study investigators will carefully monitor plasma glucose levels every 5-15 min, drawing from an indwelling peripheral IV catheter and performing the analysis using a dedicated bedside glucose analyzer. These glucose values will be used to detect and arrest any trends toward hypo or hyperglycemia and will also serve as the readout of the primary outcome - the euinsulinemic steady-state glucose (E-SSG) and hyperinsulinemic steady-state glucose (H-SSG). Serum insulin, C-peptide, growth hormone, and glucagon levels will be measured periodically during the procedure, but these results will not be available until several days later.
Mesenchymal stem cells (MSC) attract an increasing amount of attention due to their unique therapeutic properties. Yet, MSC can undergo undesirable genetic and epigenetic changes during their propagation in vitro. In this study, we investigated whether polyploidy can compromise MSC oncological safety and therapeutic properties. For this purpose, we compared the impact of polyploidy on the transcriptome of cancer cells and MSC of various origins (bone marrow, placenta, and heart). First, we identified genes that are consistently ploidy-induced or ploidy-repressed through all comparisons. Then, we selected the master regulators using the protein interaction enrichment analysis (PIEA). The obtained ploidy-related gene signatures were verified using the data gained from polyploid and diploid populations of early cardiomyocytes (CARD) originating from iPSC. The multistep bioinformatic analysis applied to the cancer cells, MSC, and CARD indicated that polyploidy plays a pivotal role in driving the cell into hypertranscription. It was evident from the upregulation of gene modules implicated in housekeeping functions, stemness, unicellularity, DNA repair, and chromatin opening by means of histone acetylation operating via DNA damage associated with the NUA4/TIP60 complex. These features were complemented by the activation of the pathways implicated in centrosome maintenance and ciliogenesis and by the impairment of the pathways related to apoptosis, the circadian clock, and immunity. Overall, our findings suggest that, although polyploidy does not induce oncologic transformation of MSC, it might compromise their therapeutic properties because of global epigenetic changes and alterations in fundamental biological processes. The obtained results can contribute to the development and implementation of approaches enhancing the therapeutic properties of MSC by removing polyploid cells from the cell population.
BACKGROUND: Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology.
METHODS: Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups.
RESULTS: At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group.
CONCLUSION: Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.
The present invention relates to a sterile in situ cross-linkable polysaccharide compositions for augmenting, filling or replacing soft tissues in various cosmetic and therapeutic applications. The composition comprises a first polysaccharide derivative functionalized with a nucleophilic group and a second polysaccharide derivative functionalized with an electrophilic group. Said nucleophilic and electrophilic functional groups spontaneously form in situ covalent linkages following co-injection in the body of a patient, resulting in the formation of a cross-linked hydrogel at the site of co-injection.The present invention relates to a sterile in situ cross-linkable polysaccharide compositions for augmenting, filling or replacing soft tissues in various cosmetic and therapeutic applications. The composition comprises a first polysaccharide derivative functionalized with a nucleophilic group and a second polysaccharide derivative functionalized with an electrophilic group. Said nucleophilic and electrophilic functional groups spontaneously form in situ covalent linkages following co-injection in the body of a patient, resulting in the formation of a cross-linked hydrogel at the site of co-injection. The invention relates to the production of preparations for topical application for cosmetic or pharmaceutical products, characterized in that a mixture of 0.1-30% phsphatidylcholine, preferably hydrated, 0.5-50% vegetable oils and/or fats and/or waxes, 10-90% aquatic and/or aqueous plant extracts, 0.1-20% monosaccharides or polysaccharides is mixed and homogenized, preferably at a temperature of 40-90°C, then cooled to 10-40°C, and then bacterial and/or yeast cultures are added.
FIELD: medicine. SUBSTANCE: for obtaining diagnostic pertussis serum for agglutinogen 1 for agglutination test a hyperimmune serum to pertussis microbe of serovar 1,0,0 or 1,2,0 is adsorbed one after another with the residue of killed pertussis culture of the same serovar and with the residue of alive parapertussis culture. In the method for obtaining diagnostic pertussis serum to agglutinogen 2 for agglutination test a hyperimmune serum of pertussis microbe of serovar 1,2,0 is adsorbed one after another with the residue of alive pertussis culture and the residue of alive parapertussis culture. In the method for obtaining diagnostic pertussis serum to agglutinogen 3 a hyperimmune serum to pertussis microbe of serovar 1,0,3 is adsorbed with the residue of alive pertussis culture. Adsorption of every serum is carried out by homogenization followed by isolation of the serum under sterile conditions, the ready-to-use serum is lyophilly dried in ampoules. The advantage lies in the fact that the sera obtained are of high specificity, high titer in agglutination test being not lower than 1:25 upon a slide and 1:1280 - in agglutination test upon plotting boards. They are standard dry preparations at moisture weight being not higher than 3%. EFFECT: higher efficiency. 10 cl
###  Teratogenic Effects

There are no adequate and well controlled studies of metronidazole in pregnant women. There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition, more than ten randomized placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known. Reproduction studies have been performed in rats, rabbits, and mice at doses similar to the maximum recommended human dose based on body surface area comparisons. There was no evidence of harm to the fetus due to metronidazole.

###  Nursing Mothers

Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels. There are no data on the effects of metronidazole on milk production. Animal studies have shown the potential for tumorigenicity after oral metronidazole was administered chronically to rats and mice (see PRECAUTIONS, Carcinogenesis, Mutagenesis, Impairment of Fertility). This drug is not intended to be administered chronically; therefore, the clinical relevance of the findings of the animal studies is unclear. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metronidazole tablets, USP and any potential adverse effects on the breastfed infant from metronidazole tablets, USP or from the underlying maternal condition. Alternatively, a nursing mother may choose to pump and discard human milk for the duration of metronidazole tablets, USP therapy, and for 48 hours after the last dose and feed her infant stored human milk or formula.

###  Geriatric Use

In elderly geriatric patients, monitoring for metronidazole associated adverse events is recommended (see CLINICAL PHARMACOLOGY, PRECAUTIONS). Decreased liver function in geriatric patients can result in increased concentrations of metronidazole that may necessitate adjustment of metronidazole dosage (see DOSAGE AND ADMINISTRATION).

###  Pediatric Use

Safety and effectiveness in pediatric patients have not been established, except for the treatment of amebiasis.
Intermittent hypoxia refers to the discontinuous use of low oxygen levels in normobaric environment. These conditions can be reproduced in hypoxic tents or chambers while the individual is training in different physical activity protocols. Intermittent hypoxia can affect several body systems, impacting nutrition, physical performance, health status and body composition. Therefore, it is necessary to assess protocols, regarding time and frequency of exposure, passive exposure or training in hypoxia, and the simulated altitude. At the molecular level, the hypoxia-inducible factor-1α is the primary factor mediating induction of target genes, including vascular endothelial growth factor and erythropoietin. The goal of these molecular changes is to preserve oxygen supply for cardiac and neuronal function. In addition, hypoxia produces a sympathetic adrenal activation that can increase the resting metabolic rate. Altogether, these changes are instrumental in protocols designed to improve physical performance as well as functional parameters for certain pathological disorders. In addition, nutrition must adapt to the increased energy expenditure. In this last context, performing physical activity in intermittent hypoxia improves insulin sensitivity by increasing the presence of the glucose transporter GLUT-4 in muscle membranes. These changes could also be relevant for obesity and type 2 diabetes treatment. Also, the anorectic effect of intermittent hypoxia modulates serotonin and circulating leptin levels, which may contribute to regulate food intake and favor body weight adaptation for optimal sport performance and health. All these actions suggest that intermittent hypoxia can be a very effective tool in sports training as well as in certain clinical protocols.
Take a single 45 mg VEOZAH tablet orally once daily with or without food.

Take VEOZAH with liquids and swallow whole. Do not cut, crush, or chew tablets.

Administer VEOZAH orally at about the same time each day. If a dose of VEOZAH is missed or not taken at the usual time, administer the missed dose as soon as possible, unless there is less than 12 hours before the next scheduled dose. Return to the regular schedule the following day.
This is an observational study in which patients diagnosed with mpox will be enrolled in two clinics in remote settings in the DR Congo (Tunda and Kole general hospital) where mpox outbreaks are ongoing. After providing informed consent, participants will undergo standard ophthalmological examinations of their eyes to see if there are any complications of mpox. This includes history taking, clinical examination, technical examinations such as a dilated fundoscopic exam, a fluorescein test and a Schirmer test, and a conjunctival swab for tear collection for monkeypox virus (MPXV) detection. Pictures of the anterior and posterior segment will also be taken to aid later verification and interpretation of the study findings. If they are hospitalised for mpox (for clinical reasons or as part of their participation in another ongoing clinical trial at the study sites), they will be followed up for 14 days and examined during an unscheduled visit in the case of new or worsening severe issues. Otherwise, patients are followed up at day 14 (for those hospitalised), day 28 and day 59. Study participants will receive the same supportive eye care as non-study participants. Study participants will be compensated for their time lost and for transportation to the clinic.

The study will primarily assess the presence of ophthalmological signs and symptoms at enrollment, but also aims to describe the complications of mpox that may arise after that point in time.
The present disclosure provides adenine base editors (ABEs) that are variants of known adenine base editors. The adenosine deaminase domain of a known ABE was modified to produce adenosine deaminase variants. The deaminase variants provided herein have broader compatibility with diverse napDNAbp domains, such as Cas homologs, for base editing applications. The ABEs provided herein comprise a deaminase variant and a napDNAbp domain. The ABEs provided herein exhibit reduced off-target editing effects while retaining high on-target editing efficiencies. These ABEs exhibit reduced off-target DNA editing effects and reduced off-target editing effects in cellular mRNA. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising the ABEs. Also provided are vectors and kits useful for the generation and delivery of the ABEs, including vector systems for engineering the ABEs through directed evolution. Cells containing such vectors and ABEs are also provided. Further provided are methods of treatment comprising administering the ABEs.
All new users of antidepressants January 1, 1996 through December 31, 2006. Individuals 18 years of age or older with medical and pharmacy benefits and at least 6 months of health plan enrollment before the first antidepressant prescription.
1. An oligonucleotide having the sequence 5'CTT CCT GTC TGA TGG CTT CT3' (SEQ ID NO: 4), inhibiting the activity of IL-8 receptor. 2. The oligonucleotide having the sequence 5' GAA AGT TTG TGC CTT ATG GA 3' (SEQ ID NO:2), inhibiting the activity of IL-8. 3. The oligonucleotides of claims 1 or 2 wherein at least a portion of the backbone is modified from the normally occuring phosphodiesterase configuration. 4. The oligonucleotides of claims 1 or 2 wherein at least one of the sugars is modified from the normal ribose configuration. 5. The oligonucleotides of claims 1 or 2 wherein at least a portion of the backbone is modified from the normally occuring phosphodiesterase configuration and at least one of the sugars is modified from the normal ribose configuration. 6. A method for treating a cancer which is at least partially mediated by IL-8 receptor said method comprising the steps of: providing a pharmaceutical containing oligonucleotide of claim 1, and administering to a patient an effective amount of an oligonucleotide. 7. The method of claim 6 wherein the step of administering comprises intratumoral injection. 8. The method of claim 6 wherein the step of administering comprises intravenous injection. 9. A method of treating a cancer, which at least partially mediated by IL-8, said method comprising the steps of: providing a pharmaceutical containing oligonucleotide of claim 2, and administering to a patient an effective amount of an oligonucleotide. 10. The method of claim 9 wherein the step of administering comprises intratumoral injection. 11. The method of claim 9 wherein the step of administering comprises intravenous injection.
This invention provides a compound of the formula (I): wherein: R1 represents a hydrogen atom, an alkyl group, etc.; R2 represents a hydrogen atom, a halogen atom, etc.; R3 represents an alkyl group, etc.; R4 represents an aryl group, etc.; A represents an aryll, etc; B represents an alkylene etc.; X represents NH, etc.; or a pharmaceutically acceptable ester of such compound, and pharmaceutically acceptable salts thereof. These compounds are useful for the treatment of medical conditions mediated by prostaglandin such as pain, fever or inflammation, etc. This invention also provides a pharmaceutical composition comprising the above compound.