anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Compsn. consists of a conventional chewing gum ground-mass into which is incorporated a basic mineral salt concentrate (pref. ground bonemeal, sea-salt, CaCO3 and NaHCO3) and, opt., other ingredients (e.g. vegetable tinctures, essential oils and resinoids, vitamins, and softening and binding agents). The purpose of the basic mineral salt concentrate is to restore the acid- base equilibrium of the whole organism and to remineralise decalcified teeth. The compsn. gives rapid and effective cleansing of the teeth against caries.
Motor PENS will be a strong tri-phasic stimulation pattern to the hip, quadriceps, hamstring, and adductors for strength training (50Hz impulses for 200ms every 1500 ms). The stimulus will be administered for 15-minutes followed by the impairment rehabilitation program.
Struvite stones or infection stones are a subset of kidney stones that are related to bacterial infection. They only make up 15% of all kidney stones, but account for a much higher percentage of mortality (up to 67%) compared to other stones-due to the infectious component. Treatment is to ensure 100% eradication of the stone with surgery followed by antibiotics to eliminate the infection. Failure to eliminate the bacteria results in the stone growing back quickly. It is unknown how long antibiotics should be administered immediately after surgery-some urologists give 2-4 weeks while others give 2-3 months. We seek to randomize patients to receive 2 weeks of antibiotics or 3 months of antibiotics after surgery to remove all the kidney stones. We will see patients at 3, 6, and 12 months with x-rays and to test their urine for bacterial infections. This is a multi-centre study with participating 12 sites across North America.
Individuals with end-stage kidney disease (ESKD) on dialysis experience high mortality and excessive burden of hospitalizations over time relative to comparable Medicare patient cohorts without kidney failure. A key interest in this population is to understand the time-dynamic effects of multilevel risk factors that contribute to the correlated outcomes of longitudinal hospitalization and mortality. For this we utilize multilevel data from the United States Renal Data System (USRDS), a national database that includes nearly all patients with ESKD, where repeated measurements/hospitalizations over time are nested in patients and patients are nested within (health service) regions across the contiguous U.S. We develop a novel spatiotemporal multilevel joint model (STM-JM) that accounts for the aforementioned hierarchical structure of the data while considering the spatiotemporal variations in both outcomes across regions. The proposed STM-JM includes time-varying effects of multilevel (patient- and region-level) risk factors on hospitalization trajectories and mortality and incorporates spatial correlations across the spatial regions via a multivariate conditional autoregressive correlation structure. Efficient estimation and inference are performed via a Bayesian framework, where multilevel varying coefficient functions are targeted via thin-plate splines. The finite sample performance of the proposed method is assessed through simulation studies. An application of the proposed method to the USRDS data highlights significant time-varying effects of patient- and region-level risk factors on hospitalization and mortality and identifies specific time periods on dialysis and spatial locations across the U.S. with elevated hospitalization and mortality risks.
The invention relates to a composition used for treating diabetes mellitus. The composition comprises an effective dosage of a composition of a compound gamma-aminobutyric acid (GABA) and a composition GABAergic thereof, or a composition of GABA and increatin. When the composition is specifically applied in-vivo in a type-I diabetes subject, with the application of GABA, beta-cell apoptosis can be inhibited, beta-cell regeneration can be promoted, autoimmune responses aiming at pancreatic islet beta-cells can be inhibited, and a substantial diabetes mellitus inversion efficacy can be achieved. The increatin described in the invention is GLP-1 or exendin-4. The effect of GLP-1/exendin-4 upon type-I diabetes is limited. However, GLP-1/exendin-4 and GABA provide a synergistic effect, and the efficacy of GABA is substantially improved. According to the invention, GABA and GLP-1/exendin-4 are simultaneously applied in-vivo in a subject, and enhanced biological effects are obtained. When GABA and GLP-1/exendin-4 are simultaneously applied in a type-I diabetes individual, hyperglycemia of diabetes mellitus can be completely inverted.
Interleukin (IL-)23 is a major mediator and therapeutic target in chronic inflammatory diseases that also elicits tissue protection in the intestine at homeostasis or following acute infection1-4. However, the mechanisms that shape these beneficial versus pathological outcomes remain poorly understood. To address this gap in knowledge, we performed single-cell RNA sequencing on all IL-23 receptor-expressing cells in the intestine and their acute response to IL-23, revealing a dominance of T cells and group 3 innate lymphoid cells (ILC3s). Unexpectedly, we identified potent upregulation of the immunoregulatory checkpoint molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on ILC3s. This pathway was activated by gut microbes and IL-23 in a FOXO1- and STAT3-dependent manner. Mice lacking CTLA-4 on ILC3s exhibited reduced regulatory T cells, elevated inflammatory T cells and more-severe intestinal inflammation. IL-23 induction of CTLA-4+ ILC3s was necessary and sufficient to reduce co-stimulatory molecules and increase PD-L1 bioavailability on intestinal myeloid cells. Finally, human ILC3s upregulated CTLA-4 in response to IL-23 or gut inflammation and correlated with immunoregulation in inflammatory bowel disease. These results reveal ILC3-intrinsic CTLA-4 as an essential checkpoint that restrains the pathological outcomes of IL-23, suggesting that disruption of these lymphocytes, which occurs in inflammatory bowel disease5-7, contributes to chronic inflammation.
In vivo studies have indicated that the absolute bioavailability of orally administered SSZ is less than 15% for parent drug. In the intestine, SSZ is metabolized by intestinal bacteria to SP and 5-ASA. Of the two species, SP is relatively well absorbed from the intestine and highly metabolized, while 5-ASA is much less well absorbed.

### Absorption:

Following oral administration of 1 g of SSZ to 9 healthy males, less than 15% of a dose of SSZ is absorbed as parent drug. Detectable serum concentrations of SSZ have been found in healthy subjects within 90 minutes after the ingestion. Maximum concentrations of SSZ occur between 3 and 12 hours post-ingestion, with the mean peak concentration (6 mcg/mL) occurring at 6 hours.

In comparison, peak plasma levels of both SP and 5-ASA occur approximately 10 hours after dosing. This longer time to peak is indicative of gastrointestinal transit to the lower intestine where bacteria mediated metabolism occurs. SP apparently is well absorbed from the colon with an estimated bioavailability of 60%. In this same study, 5-ASA is much less well absorbed from the gastrointestinal tract with an estimated bioavailability of from 10% to 30%.

### Distribution:

Following intravenous injection, the calculated volume of distribution (Vdss) for SSZ was 7.5 ± 1.6 L. SSZ is highly bound to albumin (>99.3%) while SP is only about 70% bound to albumin. Acetylsulfapyridine (AcSP), the principal metabolite of SP, is approximately 90% bound to plasma proteins.

### Metabolism:

As mentioned above, SSZ is metabolized by intestinal bacteria to SP and 5-ASA. Approximately 15% of a dose of SSZ is absorbed as parent and is metabolized to some extent in the liver to the same two species. The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours. The primary route of metabolism of SP is via acetylation to form AcSP. The rate of metabolism of SP to AcSP is dependent upon acetylator phenotype. In fast acetylators, the mean plasma half-life of SP is 10.4 hours while in slow acetylators, it is 14.8 hours. SP can also be metabolized to 5-hydroxy-sulfapyridine (SPOH) and N-acetyl-5-hydroxy-sulfapyridine. 5-ASA is primarily metabolized in both the liver and intestine to N-acetyl-5-aminosalicylic acid via a non-acetylation phenotype dependent route. Due to low plasma levels produced by 5-ASA after oral administration, reliable estimates of plasma half-life are not possible.

### Excretion:

Absorbed SP and 5-ASA and their metabolites are primarily eliminated in the urine either as free metabolites or as glucuronide conjugates. The majority of 5-ASA stays within the colonic lumen and is excreted as 5-ASA and acetyl-5-ASA with the feces. The calculated clearance of SSZ following intravenous administration was 1 L/hr. Renal clearance was estimated to account for 37% of total clearance.
The application relates to the field of antibody medicaments, in particular to development and application of a cell membrane protein F1F0-ATP synthetase antibody for inhibiting tumor angiogenesis. The present application provides an anti-F1F 0-ATP synthetase antibody comprising a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 and a light chain variable region comprising LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the sequence set forth in SEQ ID NO: 1; HCDR2 comprises the sequence shown in SEQ ID NO. 2; HCDR3 comprises the sequence shown in SEQ ID NO. 3; LCDR1 comprises the sequence shown in SEQ ID NO. 4; LCDR2 comprises the sequence shown in SEQ ID NO. 5; LCDR3 comprises the sequence shown in SEQ ID NO. 6. The application screens and obtains a monoclonal antibody (MKAB 188-5F 11) aiming at the beta subunit of the F1F0-ATP synthetase, and the monoclonal antibody selectively binds to the F1F0-ATP synthetase on the surface of a cell membrane. The monoclonal antibody has strong anti-tumor activity and is expected to be developed into an excellent anti-tumor angiogenesis antibody drug.
The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co- incubation with a peptide containing this repeat (PGEEDLPGEEDLP). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.
Efudex (5-fluorouracil) has been used as topical chemotherapy for the treatment of actinic keratoses (AKs) since the 1950's. Through many years of use, Efudex has been deemed to be a safe and effective therapy. It requires, however, a high level of patient compliance and is known to cause a vigorous inflammatory reaction when actinic keratoses are treated. It has the distinct advantage of identifying precancerous skin lesions not apparent on clinical inspection or palpation. Following a course of Efudex to the face, patients have been noted to have fewer signs of dermatoheliosis.

The investigators propose to determine if Efudex is associated with improvement of aging skin in the setting of treating actinic keratoses. The researchers hope to demonstrate less p53 staining following Efudex treatment. It is proposed that the skin improvements seen following a course of Efudex are due to both reduction of actinic keratoses and impact on photoaging. The researchers propose to quantify the effects of Efudex therapy on the immunohistochemical staining properties of facial skin with respect to p53 and procollagen. The hypothesis is that Efudex therapy will decrease p53 immunostaining thus providing biochemical evidence to support this treatment in the reduction of actinic keratoses with concomitant improvement of aging skin.
Recent years have seen growing recognition of the complexity of the role of the microbiota in shaping the immune system and its potential effects for health and disease. In particular, the gut bacteria composition has been associated with the pathogenesis of autoimmune and inflammatory diseases. Intriguingly, presence of intestinal inflammation in psoriatic arthritis (PsA) patients has been documented in several studies. Also, in genetically predisposed patients reactive arthritis, which share some of the clinical manifestations of PsA, can be triggered by certain types of bacterial gut infections. Furthermore, a recent study has reported that several intestinal bacteria including Akkermansia and Ruminoccocus, which are known to play an important role in maintaining gut homeostasis, were practically absent in PsA patients. Mechanisms through which the microbiota may be involved in the pathogenesis of PsA include an abnormal activation of the gut-associated lymphoid tissue (GALT) and/or an altered mucosal permeability thus compromising the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules.

By conducting a double-blinded, randomized, placebo-controlled trial of a non-related donor fecal microbiota transplantation (FMT) infused into the small intestine, this study will reveal whether FMT is more effective than an identically appearing placebo (saline) in reducing disease activity in psoriatic arthritis patients presenting with a minimum of three swollen joints despite at least three months of methotrexate treatment (maximal tolerable dosis ≥ 15 mg/week). All patients will throughout the study continue their individual treatment with weekly methotrexate.
The early posthatch period is crucial to intestinal development, shaping long-term growth, metabolism, and health of the chick. The objective of this study was to determine the effect of genetic selection on morphological characteristics and gene expression during early intestinal development. Populations of White Plymouth Rocks have been selected for high weight (HWS) and low weight (LWS) for over 63 generations, and some LWS display symptoms of anorexia. Intestinal structure and function of these populations were compared to a commercial broiler Cobb 500 (Cobb) during the perihatch period. Egg weights, yolk-free embryo BW, yolk weights, and jejunal samples from HWS, LWS, and Cobb were collected on embryonic day (e) 17, e19, day of hatch, day (d) 3, d5, and d7 posthatch for histology and gene expression analysis. The RNAscope in-situ hybridization method was used to localize expression of the stem cell marker, olfactomedin 4 (Olfm4). Villus height (VH), crypt depth (CD), and VH/CD were measured from Olfm4 stained images using ImageJ. mRNA abundance for Olfm4, stem cell marker Lgr5, peptide transporter PepT1, goblet cell marker Muc2, marker of proliferation Ki67, and antimicrobial peptide LEAP2 were examined. Two-factor ANOVA was performed for measurements and Turkey's HSD was used for mean separation when appropriate. Cobb were heaviest and LWS the lightest (P < 0.01). at each timepoint. VH increased in Cobb and CD increased in HWS compared to LWS (P < 0.01). PepT1 mRNA was upregulated in LWS (P < 0.01), and Muc2 mRNA was decreased in both HWS and LWS compared to Cobb (P < 0.01). Selection for high or low 8-wk body weight has caused differences in intestinal gene expression and morphology when compared to a commercial broiler.
For people with prediabetes, it may be possible to delay or prevent the progression to diabetes by reducing postprandial glucose (PPG). The Glycemic Excursion Minimization (GEM) lifestyle intervention guide can reduce PPG in people with type 2 diabetes and has been studied in this population with continuous glucose monitor (CGM) feedback to help the user learn what elevates and lowers their PPG. This study examines if the GEM lifestyle intervention guide plus continuous feedback from the FreeStyle Libre 2 CGM and FitBit will allow participants with prediabetes with HbA1c 6.0-6.4% to (1) improve their metabolic status by illustrating the effects of their routine food and physical activity choices on their glucose levels and variability, more than Routine Care (RC), and (2) to enhance these investigations by adding comprehensive plasma proteomics to the analyses. The investigators will recruit up to 36 adult participants with prediabetes through the University of Colorado, with the goal of having at least 30 participants complete the study. Participants will be randomized to the intervention or RC. Those randomized to the intervention will be given a GEM treatment manual, Libre2 CGM, and an activity monitor and will follow the GEM lifestyle intervention guide for 4 months. Those participants randomized to RC will follow recommendations from their primary care provider. RC participants will have the opportunity to receive GEM four months after consenting and completing the RC pre-post assessments if they meet eligibility criteria. It is anticipated that 50% of the RC participants will want/be able to cross over to GEM upon completion of RC. Pre-post blinded CGM data and activity data, clinical, and psychosocial outcomes will be collected and analyzed. It is anticipated that this pilot project will demonstrate the benefits of using GEM plus FreeStyle Libre 2 and FitBit to reduce percentage of CGM readings \>120 mg/dL, from blinded pre-post FreeStyle Libre Pro, as well as reduce BMI and depressive symptoms and increase modified diabetes empowerment. Comprehensive proteomics will be measured on small samples of EDTA treated venous blood. Individual proteins and protein pathways will be measured for each of the participants.
Support persons will receive written material resources on support strategies to stop smoking, and resources on how to stop smoking. Support person participants assigned to the intervention group will additionally receive a 1-call coaching session about 15-25 minutes in duration on how to support their Veteran smoker. The coaching session will be delivered by research staff by phone or video call. Veteran smokers will receive written smoking cessation resource and referral information for VHA and non-VHA EBCT options.
OBJECTIVES: The long-term outcomes comparing valve-sparing root replacement, composite valve graft with bioprosthesis, and mechanical prosthesis have yet to be explored. We investigated the long-term survival and reintervention rates after 1 of 3 major aortic root replacements in patients with tricuspid aortic valves and patients with bicuspid aortic valves.
METHODS: A total of 1507 patients underwent valve-sparing root replacement (n = 700), composite valve graft with bioprosthesis (n = 703), or composite valve graft with mechanical prosthesis (n = 104) between 2004 and 2021 in 2 aortic centers, excluding those with dissection, endocarditis, stenosis, or prior aortic valve surgery. End points included mortality over time and cumulative incidence of aortic valve/proximal aorta reintervention. Multivariable Cox regression compared adjusted 12-year survival. Fine and Gray competing risk regression compared the risk and cumulative incidence of reintervention. Propensity score-matched subgroup analysis balanced the 2 major groups (composite valve graft with bioprosthesis and valve-sparing root replacement), and landmark analysis isolated outcomes beginning 4 years postoperatively.
RESULTS: On multivariable analysis, both composite valve graft with bioprosthesis (hazard ratio, 1.91, P = .001) and composite valve graft with mechanical prosthesis (hazard ratio, 2.62, P = .005) showed increased 12-year mortality risk versus valve-sparing root replacement. After propensity score matching, valve-sparing root replacement displayed improved 12-year survival versus composite valve graft with bioprosthesis (87.9% vs 78.8%, P = .033). Adjusted 12-year reintervention risk in patients receiving composite valve graft with bioprosthesis or composite valve graft with mechanical prosthesis versus valve-sparing root replacement was similar (composite valve graft with bioprosthesis subdistribution hazard ratio, 1.49, P = .170) (composite valve graft with mechanical prosthesis subdistribution hazard ratio, 0.28, P = .110), with a cumulative incidence of 7% in valve-sparing root replacement, 17% in composite valve graft with bioprosthesis, and 2% in composite valve graft with mechanical prosthesis (P = .420). Landmark analysis at 4 years showed an increased incidence of late reintervention in composite valve graft with bioprosthesis versus valve-sparing root replacement (P = .008).
CONCLUSIONS: Valve-sparing root replacement, composite valve graft with mechanical prosthesis, and composite valve graft with bioprosthesis demonstrated excellent 12-year survival, with valve-sparing root replacement associated with better survival. All 3 groups have low incidence of reintervention, with valve-sparing root replacement showing decreased late postoperative need for reintervention compared with composite valve graft with bioprosthesis.
The investigators designed a single center, open-label, prospective study. Adults with active idiopathic inflammatory myopathies will be enrolled, meeting the Bohan \& Peter Dermatomyositis/Polymyositis(DM/PM) or Rheumatology(ACR) \& European allance of associations for rheumatology(EULAR)(2017) diagnostic criteria. Inhibitors of janus kinase including tofacitinib 5 mg once a day or twice a day and baricitinib 2mg once a day or 4mg once a day was administered for 6 months to explore its efficacy and safety, which could help to evaluate inhibitors of janus kinase's clinical characteristics and mechanism. Patients would be evaluated the improvement of clinical and laboratory indexes. Changes of symptoms, immune cell subsets and cytokines were monitored. Symptoms were evaluated by Visual Analogue Scale (VAS) of patient global and physician global, manual muscle testing(MMT-8), the Health Assessment Questionnaire(HAQ), Creatine kinase, Myositis Disease Activity Assessment Tool(MDAAT).