anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention relates to a molecular scaffold suitable for covalently binding at least one biologically active molecule to a carrier molecule, the scaffold comprising a polymeric structure and the biologically active molecules covalently bound to said polymeric structure, and wherein the scaffold further comprises a chemical group for covalently coupling of the scaffold to the carrier molecule. The biologically active molecule has a molecular weight of 3.000 Dalton or less, such as 1.700 Dalton - 1.950 Dalton. The biologically active molecule is an amphiphilic molecule in some embodiments. The biologically active molecule is a single specific molecule or is a mixture of different types of molecules, when more than one biologically active molecules are covalently bound to the polymeric (or oligomeric) structure. In particular, the invention relates to monoclonal antibody-based antibody-drug conjugates with improved therapeutic window of the drug due to covalent linkage of (a cluster of) potentiator molecules, e.g. a payload such as a protein toxin or oligonucleotide to the ADC, or alternatively, due to co-administration of an ADC and a cell-targeting conjugate comprising (a cluster of) potentiator molecules to a patient in need thereof. The invention also relates to a method for producing a scaffold suitable for covalently binding a biologically active molecule to a carrier molecule, providing a cluster of potentiator molecules. Furthermore, the invention relates to a method for producing a scaffold covalently bound to a carrier molecule, the scaffold comprising a covalently bound biologically active molecule, the carrier molecule comprising an antibody and a payload.
Tobacco vein necrosis (TVN) is a complex phenomenon regulated by different genetic determinants mapped in the HC-Pro protein (amino acids N330, K391 and E410) and in two regions of potato virus Y (PVY) genome, corresponding to the cytoplasmic inclusion (CI) protein and the nuclear inclusion protein a-protease (NIa-Pro), respectively. A new determinant of TVN was discovered in the MK isolate of PVY which, although carried the HC-Pro determinants associated to TVN, did not induce TVN. The HC-Pro open reading frame (ORF) of the necrotic infectious clone PVY N605 was replaced with that of the non-necrotic MK isolate, which differed only by one amino acid at position 392 (T392 instead of I392). The cDNA clone N605_MKHCPro inoculated in tobacco induced only weak mosaics at the systemic level, demostrating that the amino acid at position 392 is a new determinant for TVN. No significant difference in accumulation in tobacco was observed between N605 and N605_MKHCPro. Since phylogenetic analyses showed that the loss of necrosis in tobacco has occurred several times independently during PVY evolution, these repeated evolutions strongly suggest that tobacco necrosis is a costly trait in PVY.
Even though there some studies showing good outcomes using absorbable sutures in skin closure in clean surgical wounds, ED based studies still need to be conducted to convince ED physicians that the use of absorbable sutures to close the skin in traumatic lacerations are just as acceptable as traditional non-absorbable sutures. Use of absorbable sutures confers several advantages over non-absorbable sutures. For one, patients do not need an additional physician visit either in the office, or more often that not, in the emergency department. These visits add to ED overcrowding, prolonged length of ED stay and are often not reimbursed if seen in the emergency department. Moreover, adult patients need to miss work or school and children often have to miss school or daycare to have these sutures removed. The potential to avert another traumatic experience from suture removal in children who had been restrained for suture placement is another advantage of using absorbable sutures over non-absorbable sutures.
INTRODUCTION: Recurrent shoulder dislocations often cause attrition of the labrum and progressive loss of the anterior bony contour of the glenoid. Treatment options for this pathology involve either soft tissue repair or bony augmentation procedure. The optimal management for patients with shoulder instability with subcritical bone loss remains unknown and current clinical practice is highly varied.
METHODS AND ANALYSIS: The Shoulder instability Trial comparing Arthroscopic stabilisation Benefits compared with Latarjet procedure Evaluation (STABLE) is an ongoing multicentre, randomised controlled trial of 114 patients diagnosed with recurrent anterior shoulder instability and subcritical glenoid bone loss (10%-20%, measured on 3D CT using circle of best fit technique). Patients are randomised either arthroscopic capsuloligamentous repair (Bankart repair+remplissage) or open or arthroscopic coracoid transfer (Latarjet procedure). The primary outcome of this trial will be the between-group difference in the change from baseline to 24 months postintervention in Western Ontario Shoulder Instability Index scores. Secondary outcomes include: (1) rates of recurrent shoulder dislocations and symptoms of instability up to 24 months' postsurgery; (2) clinical outcomes measured by American Shoulder and Elbow Society score, Shoulder Activity Scale, EQ-5D and Patient Satisfaction Scale; (3) physical examination (range of motion, stability); (4) return to previous level of activity/sport; (5) rate of shoulder-related complications and serious adverse events.
ETHICS AND DISSEMINATION: This protocol has been reviewed and approved by the Hamilton Integrated Research Ethics Board (HiREB; project number 15998) prior to commencement of the trial. Results from the study will be submitted for publication in a peer-reviewed journal regardless of whether there are statistically significant findings.
TRIAL REGISTRATION NUMBER: NCT05705479; this study was prospectively registered on clinicaltrials.gov.
BACKGROUND: This study evaluated blood glucose (BG), creatinine levels, metabolic issues, length of stay (LOS), and early postoperative complications in diabetic primary total knee arthroplasty (TKA) patients. It examined those who continued home oral antidiabetic medications and those who switched to insulin postoperatively. The hypothesis was that continuing home medications would lead to lower BG levels without metabolic abnormalities.
METHODS: Patients who had diabetes who underwent primary TKA from 2013 to 2022 were evaluated retrospectively. Diabetic patients who were not on home oral antidiabetic medications or who were not managed as an inpatient postoperatively were excluded. Patient demographics and laboratory tests collected preoperatively and postoperatively as well as 90-day emergency department visits and 90-day readmissions, were pulled from electronic records. Patients were grouped based on inpatient diabetes management: continuation of home medications versus new insulin coverage. Acute postoperative BG control, creatinine levels, metabolic abnormalities, LOS, and early postoperative complications were compared between groups. Multivariable regression analyses were performed to measure associations.
RESULTS: A total of 867 primary TKAs were assessed; 703 (81.1%) patients continued their home oral antidiabetic medications. Continuing home antidiabetic medications demonstrated lower median maximum inpatient BG (180.0 mg/dL versus 250.0 mg/dL; P < .001) and median average inpatient BG (136.7 mg/dL versus 173.7 mg/dL; P < .001). Logistic regression analyses supported the presence of an association (odds ratio = 17.88 [8.66, 43.43]; P < .001). Proportions of acute kidney injury (13.5 versus 26.7%; P < .001) were also lower. There was no difference in relative proportions of metabolic acidosis (4.4 versus 3.7%; P = .831), LOS (2.0 versus 2.0 days; P = .259), or early postoperative complications.
CONCLUSIONS: Continuing home oral antidiabetic medications after primary TKA was associated with lower BG levels without an associated worsening creatinine or increase in metabolic acidosis.
LEVEL III EVIDENCE: Retrospective Cohort Study.
The invention belongs to the field of genetic engineering, discloses a streptococcus thermophilus derived target sequence recognizable by a CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR associated 9) system and further discloses a sgRNA (single guide ribonucleic acid) and a coding DNA (deoxyribonucleic acid) molecule thereof. The target sequence is shown as n-20th of any one of SEQ ID NO:1-63, wherein n=1-5. A sequence of the sgRNA is 5'-recognition sequence- Cas9 protein recruitment sequence-3', and a DNA sequence corresponding to the recognition sequence is identical to the target sequence. The invention also discloses the CRISPR-Cas9 system, and the CRISPR-Cas9 system comprises Cas9 proteins and sgRNA and/or comprises carriers carrying a Cas9 protein coding sequence and a sgRNA coding sequence. The invention further discloses application of the CRISPR-Cas9 system to CXCR4 gene editing and preparation of medicines for treating HIV (human immunodeficiency virus) infection. CXCR4 gene editing can be realized to protect cells from HIV infection.
PCT No. PCT/JP96/00917 Sec. 371 Date Jan. 8, 1998 Sec. 102(e) Date Jan. 8, 1998 PCT Filed Apr. 3, 1996 PCT Pub. No. WO96/31529 PCT Pub. Date Oct. 10, 1996The present invention relates to a peptide having the following amino acid sequence: Ala-Xaa1-Leu-Xaa2-Phe-Xaa3-Xaa4-Xaa5-(Xaa6)n (wherein Xaa1 and Xaa4 each independently represents an amino acid residue which may have an alkyl or heteroalkyl side chain which may be substituted by a hydroxy, amino or guanidyl group; Xaa2 and Xaa6 each independently represents an amino acid residue which may have an alkyl or heteroalkyl side chain which may be substituted by a hydroxyl group; Xaa3 and Xaa5 each independently represents an amino acid residue which may have a hydrophobic side chain; and n stands for 1 or 0), or derivatives thereof; and a modification thereof. The peptide or derivatives thereof according to the present invention is useful as a pharmaceutical composition for the prevention and treatment of autoimmune diseases, rejection reaction attendant on the organ transplantation, inflammation or the like.
Circular RNAs have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of this protocol will investigate the expression pattern of circular RNA (circRNA) by bioinformatics analysis in patients with acute ischemic stroke and healthy control. The candidate circRNA will be verified as biomarkers for the detection and prognosis of acute ischemic stroke. Distinctive expression patterns of circRNA will be identified by individual quantitative real time polymerase chain reaction (qRT-PCR). A diagnostic or predictive model will be established using logistic regression. The panel of these altered circRNAs may be associated with acute IS and could serve as a novel diagnostic or predictive method.
Drop 5 ml of sirolimus oral solution and 5 g of dressing into the mixed bottle. Apply mixed gel of topical sirolimus to affected area. Use it twice a day for 6 months.
An articular chondrocyte having the ability to mineralise calcium is described. The chondrocyte may be mature, or of foetal origin, and may be provided as a cell-line, preferably of human origin. The chondrocyte may comprise an oncogene, which is preferably temperature-sensitive, especially the SV40T antigen. The cell-line may be produced by a process involving an immortalisation agent, which may comprise the oncogene. The cell-lines may be used to identify therapeutic agents for the treatment of arthritis. There is also described a human hypertrophic cell-line, in which the cells may have the features described, and may be prepared by a process analogous to that defined above. The cells may be used to produce joint matrix tissue for use in the repair and/or replacement of damaged tissue, or for use in the identification of therapeutic agents for the treatment of arthritis.
LPS induced sepsis is a complex process involving various immune cells and signaling molecules. Dysregulation of macrophage polarization and ROS production contributed to the pathogenesis of sepsis. PGP is a transmembrane transporter responsible for the efflux of a number of drugs and also expressed in murine macrophages. Natural products have been shown to decrease inflammation and expression of efflux transporters. However, no treatment is currently available to treat LPS induced sepsis. Verapamil and Tangeretin also reported to attenuate lipopolysaccharide-induced inflammation. However, the effects of verapamil or tangeretin on lipopolysaccharide (LPS)-induced sepsis and its detailed anti-inflammatory mechanism have not been reported. Here, we have determined that verapamil and tangeretin protects against LPS-induced sepsis by suppressing M1 macrophages populations and also through the inhibition of P-glycoprotein expression via downregulating STAT1/STAT3 and upregulating SOCS3 expression in macrophages. An hour before LPS (10 mg/kg) was administered; mice were given intraperitoneal injections of either verapamil (5 mg/kg) or tangeretin (5 mg/kg). The peritoneal macrophages from different experimental groups of mice were isolated. Hepatic, pulmonary and splenic morphometric analyses revealed that verapamil and tangeretin decreased the infiltration of neutrophils into the tissues. Verapamil and tangeritin also enhanced the activity of SOD, CAT, GRX and GSH level in all the tissues tested. verapamil or tangeretin pre-treated mice shifted M1 macrophages to M2 type possibly through the inhibition of P-glycoprotein expression via downregulating STAT1/STAT3 and upregulating SOCS3 expression. Hence, both these drugs have shown protective effects in sepsis via suppressing iNOS, COX-2, oxidative stress and NF-κB signaling in macrophages. Therefore, in our study we can summarize that mice were treated with either Vera or Tan before LPS administration cause an elevated IL-10 by the macrophages which enhances the SOCS3 expression, and thereby able to limits STAT1/STAT3 inter-conversion in the macrophages. As a result, NF-κB activity is also getting down regulated and ultimately mitigating the adverse effect of inflammation caused by LPS in resident macrophages. Whether verapamil or tangeretin offers such protection possibly through the inhibition of P-glycoprotein expression in macrophages needs clarification with the bio availability of these drugs under PGP inhibited conditions is a limitation of this study.
Half of the study sample will be allocated to EECP therapy (35 sessions) of 1-hour each. Acetazolamide challenged HMPAO-SPECT will be performed before randomization and repeated 2-months after the completion of EECP therapy. MRI of the brain would be performed after completion of EECP therapy to document any silent stroke.
Atypical antipsychotic (AA) medications are associated with obesity, diabetes mellitus, dyslipidemia, and cardiovascular disease.1 The prevalence of obesity in the AA medicated population ranges from 40-60%, compared to 30% of the general population. Treatments that are aimed at either reducing the burden of obesity in psychotic illness or preventing the weight gain and other metabolic changes associated with AA are needed. One potential therapy that has received inadequate clinical evaluation is Green tea (Camillia sinensis; GT). GT contains flavonoids including epigallocatechin gallate (EGCG), as well as caffeine, that have been documented to promote weight and fat loss in normal to overweight healthy subjects. Recently green tea was shown to significantly decrease plasma LDL and triglyceride concentrations and increase HDL concentrations in obese women. GT has never been evaluated for its potential to prevent weight gain or changes in plasma lipid concentrations in patients initiating therapy with AA. However, case reports of individuals indicate that treatment with a green tea extract may have efficacy in preventing weight gain in 4 patients that initiated treatment with quetiapine.

We hypothesize that intake of GT in the form of a dietary supplement will result in significantly less weight gain than supplementation with placebo in patients initiating therapy with Zyprexa®. We propose to conduct an 12-week double-blind, placebo-controlled pilot study of 48 out-patient volunteers to determine if twice daily supplementation with GT 1) attenuates weight and fat gain in patients initiating therapy with Zyprexa® and 2) attenuates changes in cardiovascular risk factors including plasma lipoprotein and triglyceride concentrations. The experiments will be performed on patients who initiate therapy with Zyprexa® with a BMI \< 40kg/m2 that do not have dyslipidemia requiring pharmacologic intervention.
In toxicity studies in rats and monkeys of up to 26-week and 39-week duration, respectively, findings included vasodilation, increases in serum calcium, decreases in serum phosphorus, and soft tissue mineralization at doses ≥10 mcg/kg/day. The 10 mcg/kg/day dose resulted in systemic exposures to abaloparatide in rats and monkeys that were 2 and 3 times, respectively, the exposure in humans at daily subcutaneous doses of 80 mcg.

Pharmacologic effects of abaloparatide on the skeleton were assessed in 12- and 16-month studies in ovariectomized (OVX) rats and monkeys, at doses up to 11- and 1-times human exposure at the recommended subcutaneous dose of 80 mcg, respectively (based on AUC comparisons). In these animal models of postmenopausal osteoporosis, treatment with abaloparatide resulted in dose-dependent increases in bone mass at vertebral and/or nonvertebral sites, correlating with increases in bone strength. The anabolic effect of abaloparatide was due to the predominant increase in osteoblastic bone formation and was evidenced by increases in trabecular thickness and/or cortical thickness due to endosteal bone apposition. Abaloparatide maintained or improved bone quality at all skeletal sites evaluated and did not cause any mineralization defects.

In an 8-week study in androgen-deficient orchiectomized (ORX) male rats, a male osteoporosis model, the effects of 5 and 25 mcg/kg/day abaloparatide (≥47-fold clinical exposures by AUC) were examined on bone formation, bone mass, and bone strength. Abaloparatide induced bone formation and improved cortical and trabecular BMD, geometry, and architecture without increasing parameters of bone resorption.
Voltage-gated sodium (Nav) channels are crucial in transmitting action potentials in neurons. The tetrodotoxin-resistant subtype Nav1.8 is predominantly expressed in the peripheral nervous system, offering a unique opportunity to design selective inhibitors for pain relief. A number of compounds have been reported to specifically block Nav1.8. Among these, VX-548 is already in regulatory review for the treatment of moderate-to-severe acute pain and holds the promise to be the first non-opioid pain killer over the past twenty years. Recent structural studies using cryogenic electron microscopy (cryo-EM) and structure-based predictive modeling have provided unprecedented insights into the structural pharmacology of Nav1.8. In this review, we summarize the latest developments in Nav1.8-selective inhibitors, focusing on the druggable sites and mechanisms that confer subtype specificity. These structural insights highlight the potential for Nav1.8 inhibitors to deliver non-addictive pain management, thus illuminating the avenue to next-generation analgesic development.
Patients in the rocuronium/sugammadex group will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction. Additional rocuronium will be given to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 twitches.
Every participant receives general anesthesia and a modified pectoral nerve block for breast surgery. Participants of this arm receive single-shot ropivacaine (0,2%, 30ml) plus 2ml placebo (NaCl 0,9%).
The current study aimed to construct the growth curve and find the best-fitting non-linear model for the Nili-Ravi buffalo calves. The pedigree and monthly body weight data for 6644 calves born between 2010 and 2020 (inclusive) in six herds, maintained in different geographical regions of Punjab were collected. The study was performed under a longitudinal design and various non-linear models were used to associate the age with weight by using the easyreg package in R studio. Finally, the genetic parameters of growth curve were estimated through the bi-variate sire model in ASReml (v4.2). The model with the highest value of coefficient of determination and the lowest values of Akaike's information criterion, Bayesian information criterion, and root-mean-square error was considered as the best fit for defining the growth curve. The Brody model was found as the best fitted model with the values of 0.6648, 627871.80, 627908.10, and 30.793 for the R2adj, AIC, BIC, & RMSE respectively, for the combined dataset. The values of growth curve parameters for the Brody model were 943.99 ± 101.38Kg (A), 0.96 ± 0.004Kg (B), and 0.0005 ± 0.00Kg (K) for all animals. A higher K-value of females indicates their early maturity compared with male animals in this breed. The heritability estimates for the growth curve traits were low, while the values of genetic correlations were higher than those of phenotypic correlations. The data revealed that Asymptotic weight (A) and birth weight (B) were positively correlated with each other, while the rate of maturity (K) was negatively correlated with initial and final body weights.
Radiostereometric Analysis, or RSA, is an accurate in vivo measurement technique using two simultaneous radiographs. It provides researchers with three dimensional motion analyses to look not only at routine flexion/extension, but also other rotational and translational changes. The measurement accuracy offered by this technique far exceeds the manual techniques currently used. Utilization of the RSA technology at the IHP and the United States is in its infancy. The investigators have placed much effort over the past 2-3 years to put the necessary dedicated resources and personnel in place. This has been a collaborative effort between the Department of Orthopedic Surgery and the Imaging Core at IHP. Preliminary work on the accuracy, reliability, and surgical planning for use of RSA has been completed and presented at national conferences.

The purpose of this study is to assess the amount of motion in the lumbar spine in patients with the AST Stabilimax BAR. The AST Stabilimax BAR is designed to allow for motion in the spine while providing the necessary stability to the spinal segment. The amount and degree of this motion is currently unknown clinically, but has been biomechanically tested in vitro. By using tantalum bead markers placed in the spine at the time of the surgery, RSA analysis can determine the amount and degree of motion the implant provides. Two questions will be examined with this data: 1) what is the amount of sagittal and coronal plane motion that occurs in vivo with the AST Stabilimax BAR system? and 2) will this change over the 2 year time frame for this study?