anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein- mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a praracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autorcine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkk1, we believe that the G171V mutation may cause an incrase in Wnt activity in osteoblasts by reducing the number of targets for paracrine Dkk1 to antagonize without affecting the activity of autocrine Wnt.
The investigators at Rockefeller University Hospital are engaged in research on the nature, diagnosis and treatment of obesity and diabetes. The investigators are trying to find out why insulin, a blood sugar lowering hormone that is released by the pancreas following a meal, does not work effectively in individuals with obesity or type 2 diabetes. The investigators have recently discovered a protein in fat cells of obese mice that helps fat cells to take up and break down sugar from the blood. This protein (called FOXA2) also prevents the generation of more fat cells. FOXA2 is only present in obese mice, but absent from fat stores of lean animals. Insulin can stimulate the production of FOXA2 in fat cells. Furthermore, the levels of FOXA2 protein correlate with the degree of blood insulin levels. In this study, we are would like to determine whether FOXA2 is also produced in fat cells of humans, and if its level correlates with the degree of obesity and insulin resistance.
Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Recombinant DNA molecule comprising a nucleotide sequence coding for hepatitis B surface antigen (HBsAg) and a regulatory region derived from the yeast arg 3 gene to effect transcription of the HBsAg sequence in yeast is new. Micro-organism transformed with the DNA molecule defined above is new. - Vector comprising the yeast arg 3 regulatory region and a restriction site near to it so that a protein synthesised by expression of a coding sequence inserted into the restriction site is free from extraneous amino acid residues is new. Vaccine for stimulation of protection against hepatitis B virus (HBV) infection comprises HBsAg produced by a micro-organism as defined above. - The vaccine stimulants protection in humans against HBV infection on parenteral admin. The DNA fragment and the HBsAg produced by it can be used as a probe for detection of HBV in biological samples by DNa hybridisation techniques and immunoassays. EPAB- EP-106828 B Recombinant DNA molecule comprising a nucleotide sequence which codes for HBsAg and a regulatory region which can effect transcription in yeast, the said sequence being expressed as a polypeptide that retains the immunogenicity of HBsAg and comprises the HBsAg polypeptide of 226 amino acids and a polypeptide extension at its N-terminal end, characterised in that the extension is a polypeptide at least a portion of which is not derived from the pre-S region, in which the sequence comprises a sequence which codes for an extension comprising both a polypeptide which is derived from the pre-S region and a polypeptide which is not derived therefrom, and in which the sequence comprises a sequence which codes for an extension which is derived from the pre-S region and is composed of a sequence containing up to the 42 N-terminal amino acids which naturally precede the HBsAg polypeptide of 226 amino acids. (Dwg.0/5) - EP-106828 B Recombinant DNA molecule comprising a nucleotide sequence which codes for HBsAg and a regulatory region which can effect transcription in yeast, the said sequence being expressed as a polypeptide that retains the immunogenicity of HBsAg and comprises the HBsAg polypeptide of 226 amino acids and a polypeptide extension at its N-terminal end, characterised in that the extension is a polypeptide at least a portion of which is not derived from the pre-S region, in which the sequence comprises a sequence which codes for an extension comprising both a polypeptide which is derived from the pre-S region and a polypeptide which is not derived therefrom, and in which the sequence comprises a sequence which codes for an extension which is derived from the pre-S region and is composed of a sequence containing up to the 42 N-terminal amino acids which naturally precede the HBsAg polypeptide of 226 amino acids. (Dwg.0/5)
Brief motivational interventions (BMIs) to reduce risky drinking in college students are well established as beneficial, but the needs of emerging adult (EA) risky drinkers who live in disadvantaged communities and are not fulltime college students have been neglected. They tend to have more constrained access to rewarding opportunities, adult roles, and activities that present pro-social alternatives to heavy drinking. When coupled with the foreshortened time horizons typical of many EAs, this suggests the need for interventions that not only enhance motivation to reduce drinking, but guide EAs to engage in alternatives to heavy drinking and orient their behavior toward longer-term positive goals. Guided by behavioral economics (BE), this study will disseminate and evaluate a brief motivational BE intervention that combines BMI elements with the Substance Free Activity Session shown to reduce drinking by increasing future orientation and engagement in pro-social alternatives. The intervention will be delivered using a digital platform appropriate for EAs whose social networks operate through such communications. Because peers influence substance use, a peer-driven sampling method (Respondent Driven Sampling \[RDS\]) will be used to recruit 500 community-dwelling EAs ages 18-28 for a cluster randomized controlled trial that compares the intervention with a health education control condition. Additional EA target population members ("seed" participants, n = 250) will start RDS recruitment but are not part of the intervention evaluation sample. The evaluation study will assess participants' drinking practices and problems, BE outcome predictors, and social networks at enrollment and at 1, 6, and 12-month follow-ups. Intervention efficacy and behavior change mechanisms will be examined. Reduced alcohol demand and delay discounting and favorable post-intervention shifts in future orientation, substance-free vs. substance-involved activities, and use of protective behavioral strategies to reduce drinking-related harms are predicted to mediate intervention effects. Social network analysis will assess whether the intervention attenuates network promotion of individual drinking. The study will be the first to test a web-based alcohol reduction intervention focused on BE principles and to use digital RDS to reach community-dwelling EAs for intervention. The study will translate and test BE mediators and moderators of change, and the digital intervention has high potential for reach and scalability with under-served community risk groups.
Provided herein is an antibody (e.g., an isolated antibody) that specifically binds an epitope (e.g., linear epitope) within amino acids spanning the extracellular portion of human IL-13RA2. In some embodiments, the amino acids spanning the extracellular portion of human IL-13RA2 have at least 90% identity with the corresponding canine sequence of IL-13RA2. In some embodiments, the antibody specifically binds both human and canine IL-13RA2. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a recombinant antibody. In some embodiments, the antibody is humanized. In some embodiments, the antibody is the monoclonal antibody produced by hybridoma 1E10B9 or a recombinant form thereof.
This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date of enrollment in Study 165-501 (incident-users) or who have previously started treatment with pegvaliase at the date of enrollment in Study 165-501 (prevalent-users) are eligible for participation in Study 165-503. Subjects participating in the 165-501 study who consent to participate in this study (165-503) will be requested to provide pre-dose blood samples for Phe, immunologic and inflammatory marker testing approximately every 3 months for the first 3 years of participation, then every 6 months for the remainder of the study. Subjects will be requested to provide additional pre-dose blood samples at the time of Study 165-501 -protocol defined safety events. Additional pre-dose samples will be drawn as per standard of care as detailed in protocol 165-501. The blood Phe, immunologic (PAL IgG, PEG IgG, PEG IgM, anti-pegvaliase IgE), and inflammatory (C3/C4, hsCRP) markers, will be sent to a central laboratory for processing. Data collected in the 165-501 study will be combined with the data collected in this study to decrease burden on sites for data entry and to avoid duplication of ADR reporting (see Criteria for Evaluation). The combined data will be reported in the Clinical Study Report for this study. Subjects can withdraw from Study 165-503 and remain on Study 165-501, but they cannot withdraw from Study 165-501 and remain on Study 165-503 as safety events and other data-points are collected in Study 165-501.
Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) aims to optimize the peroperative detection and removal of PSMA-avid lymph node (LN) metastases (LNMs) and has been described in patients with recurrent prostate cancer (PCa). In newly diagnosed PCa patients undergoing pelvic LN dissections, PSMA RGS could guide the urologist toward PSMA-expressing LNMs as identified on preoperative 18F-PSMA PET/CT imaging. The objective was to evaluate the safety and feasibility of 111In-PSMA RGS in primary PCa patients with one or more suggestive LNs on preoperative 18F-PSMA PET/CT. Methods: This prospective, phase I/II study included 20 newly diagnosed PCa patients with at least 1 suggestive LN on preoperative 18F-PSMA PET/CT. PSMA RGS was performed 24 h after 111In-PSMA-I&T administration, and postoperative 18F-PSMA PET/CT was performed to verify successful removal of the suggestive lesions. The primary endpoint was determination of the safety and feasibility of 111In-PSMA RGS. Safety was assessed by monitoring adverse events. Feasibility was described as the possibility to peroperatively detect suggestive LNs as identified on preoperative imaging. Secondary outcomes included the accuracy of 111In-PSMA RGS compared with histopathology, tumor- and lesion-to-background ratios, and biochemical recurrence. Results: No tracer-related adverse events were reported. In 20 patients, 43 of 49 (88%) 18F-PSMA PET-suggestive lesions were successfully removed. 111In-PSMA RGS facilitated peroperative identification and resection of 29 of 49 (59%) RGS-target lesions, of which 28 (97%) contained LNMs. Another 14 of 49 (29%) resected LNs were not detected with 111In-PSMA RGS, of which 2 contained metastases. Conclusion: 111In-PSMA RGS is a safe and feasible procedure that allows peroperative detection of 18F-PSMA PET/CT-suggestive lesions in newly diagnosed PCa patients. The use of a radioactive PSMA tracer and a detection device (γ-probe) during surgery helps in identifying LNs that were suggestive of PCa metastases on the 18F-PSMA PET/CT before surgery and thus may improve the peroperative identification and removal of these LNs.
PURPOSE: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center.
METHODS: A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control.
RESULTS: Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT.
CONCLUSION: Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.
INTRODUCTION: Anterior lumbar interbody fusion (ALIF) can treat spondylolisthesis, degenerative disc disease and pseudoarthrosis. This approach facilitates complete discectomy, disc space distraction, indirect decompression of neural foramina and placement of large interbody devices. Several intra- and postoperative complications can be attributed to the anterior approach: vascular/visceral injury, hypogastric plexus injury and urogenital consequences. Spine-specific complications include implant migration, graft failure, pseudoarthrosis and persistent symptomology.
METHODS: This retrospective study reviewed patient demographics, medium-term outcomes and complication rates following ALIF surgery performed over a 5-year period. A total of 110 consecutive patients had undergone ALIF surgery at a single tertiary spinal centre. The database was reviewed with a primary outcome of identifying postoperative 90-day complications and whether a revision anterior operation was required after primary ALIF.
RESULTS: No patients required revision anterior operation after their primary ALIF surgery by final follow-up. Out of 110 patients, 11 (10%) recorded a complication attributed to the anterior stage of their operation within 90 days.
CONCLUSIONS: Our 90-day complication rate of 10% lies within the 2.6% acute complication and 40% overall complications rates described in previous literature. The risk of vascular/visceral injury is significant (3%) and we recommend that ALIF be performed as a dual surgeon procedure with a vascular-trained access surgeon accompanying the spinal surgeon. ALIF is a valid revision surgical option for failed posterior approaches leading to complications such as pseudoarthrosis. In our sample, 89% of patients were managed with posterior fixation to augment the anterior fusion as, biomechanically, this is a proven construct.
We present an approach to computing the probability of epidemic "burnout," i.e., the probability that a newly emergent pathogen will go extinct after a major epidemic. Our analysis is based on the standard stochastic formulation of the Susceptible-Infectious-Removed (SIR) epidemic model including host demography (births and deaths) and corresponds to the standard SIR ordinary differential equations (ODEs) in the infinite population limit. Exploiting a boundary layer approximation to the ODEs and a birth-death process approximation to the stochastic dynamics within the boundary layer, we derive convenient, fully analytical approximations for the burnout probability. We demonstrate-by comparing with computationally demanding individual-based stochastic simulations and with semi-analytical approximations derived previously-that our fully analytical approximations are highly accurate for biologically plausible parameters. We show that the probability of burnout always decreases with increased mean infectious period. However, for typical biological parameters, there is a relevant local minimum in the probability of persistence as a function of the basic reproduction number [Formula: see text]. For the shortest infectious periods, persistence is least likely if [Formula: see text]; for longer infectious periods, the minimum point decreases to [Formula: see text]. For typical acute immunizing infections in human populations of realistic size, our analysis of the SIR model shows that burnout is almost certain in a well-mixed population, implying that susceptible recruitment through births is insufficient on its own to explain disease persistence.
An orthopedic system configured for use in a pre-operative, intra-operative, and post-operative assessment. The orthopedic system comprises a first screw, a second screw, a first device, a second device, and a computer. The first device and the second device are respectively coupled to a first bone and a second bone of a musculoskeletal system. The first and second devices each include electronic circuitry, one or more sensors, and an IMU. A bracket, wrap, or sleeve can be used to hold the first and second devices to the musculoskeletal system. The first and second devices are configured to send measurement data to a computer. The first and second devices each have an antenna system. Electronic circuitry in the first or second devices are configured to harvest energy from a received radio frequency signal to recharge a battery to maintain operation.
BACKGROUND/AIMS: The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC.
METHODS: A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test.
RESULTS: Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01).
CONCLUSION: Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.
Provided herein are HER2-targeting molecules comprising Shiga toxin A Subunit derived polypeptides having 1) de-immunization and 2) reduced, protease-cleavage sensitivity while retaining Shiga toxin function(s), such as,  e.g. , potent cytotoxicity via ribosome inhibition. Certain HER2-targeting molecules of the present invention exhibit reduced immunogenic potential in mammals and are well-tolerated by mammals while retaining aforementioned features. The HER2-targeting molecules of the present invention have uses for selectively killing specific cells ( e.g. , HER positive tumor cells); for selectively delivering cargos to specific cells ( e.g. , HER positive tumor cells), and as therapeutic and/or diagnostic molecules for treating and diagnosing a variety of conditions, including cancers and tumors involving the expression or over-expression of cell-surface HER2.
Catechins and Procyanidins of Ginkgo biloba Show Potent Activities on Inhibition of Beta-Amyloid Peptide Aggregation and Destabilization of Preformed Fibrils In this invention, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with the reference compounds, six of them were identified as catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, procyanidins B1 and B3. The activities of these polyphenols on A342 aggregation inhibition and preformed fibrils destabilization were assayed. The bioassay results showed that all the polyphenols and fractions of EGb containing catechins and procyanidins exerted potent activities on A342 aggregation inhibition and could also destabilize the performed fibrils. Therefore, catechins and procyanidins could be regarded as potent active constituents of EGb of A342 aggregation inhibition and the fibrils destabilization. <DocRef#00 129238-YW > M006.038.DRF 18 Spec Draft v.final
Dispersing compositions comprise (1) a polyoxyethylene derivative of a monoester of sorbitan with a higher fatty acid having from 16 to 18 carbon atoms and (2) a lower polyethylene glycol having an average molecular weight in the range of from 200 to 600, the ratio by weight of said polyoxyethylene ester (1) to said glycol, (2) being from 4 : 3 to 9 : 1 respectively.  Suitable sorbitan ester derivatives are the polyoxyethylene derivatives of sorbitan monopalmitate, sorbitan monooleate and sorbitan monostearate.  Polyethylene glycols specified are those having average molecular weight of 200, 300, 400 and 600. The dispersing compositions are used for preparing rapidly water-dispersible Vitamin A fatty acid ester compositions (see Division A5).ALSO:A stable, readily water-dispersible Vitamin A ester composition comprises a Vitamin A higher fatty acid ester, wherein the acyl moiety of the ester has at least eight carbon atoms, and in admixture therewith and as dispersing agent therefor a mixture of (1) a polyoxyethylene derivative of a monoester of sorbitan with a higher fatty acid having from 16 to 18 carbon atoms and (2) a lower polyethylene glycol having an average molecular weight that is in the range of 200 to 600, said Vitamin A ester being present in said composition up to 20% by weight of the total and the ratio by weight of (1) to (2) being from 4 : 3 to 9 : 1 when said Vitamin A concentration is below 10% and from 4 : 3 to 5 : 1 when said Vitamin A concentration is at least 10%.  The preferred Vitamin A esters are Vitamin A palmitate, Vitamin A corn oil fatty acid esters and Vitamin A coconut oil fatty acid esters. Sweetening and flavouring agents and preservatives such as methyl and propyl paraben may be added to the compositions.  The compositions are used to form stable, aqueous Vitamin A solutions and may also be employed in the form of gelatine capsules, and in aqueous dispersions containing also water-soluble vitamins.