anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The proposed work should help move toward the long-term goal of selection of antihypertensive drug therapy based on a patient's genetic make-up. Hypertension (HTN) is the most common chronic disease for which drugs are prescribed, and the most prevalent risk factor for heart attack, stroke, renal failure and heart failure. Responses to antihypertensive drug therapy exhibit considerable interpatient variability, contributing to poor rates of HTN control (currently about 40-50% in the US), and frequent nonadherence and dropout from therapy. We propose to identify genetic predictors of the antihypertensive and adverse metabolic responses to two preferred and pharmacodynamically contrasting drugs, a beta-blocker (metoprolol) and a thiazide diuretic (chlorthalidone) in a sequential monotherapy design in 400 hypertensive individuals. Data collected will include home and clinic blood pressure, blood samples for testing for adverse metabolic effects and other biomarkers, RNA, and DNA and urine sample. We will conduct genome-wide association single nucleotide polymorphism (SNP) genotyping and data from the study will be used for replication of findings from the previous PEAR trial, along with new discoveries. The primary aims are to define the genetic determinants of the antihypertensive response and adverse metabolic responses (e.g. changes in glucose, triglycerides and uric acid). The proposed research is significant because genetically-targeted antihypertensive therapy could lead to dramatically higher response rates and fewer adverse effects than the usual trial-and-error approach. This would likely lead to higher rates of HTN control, less need for polypharmacy, reduced health care costs, and improved outcomes.
The present invention relates to negative function modulators of at least one variant of non-erythropoietic erythropoietin (V-EPO) and pharmaceutical compositions or kits containing the same. The negative function modulator of V-EPO may be a monospecific or multispecific antibody anti-EV 3, anti-EV 4, anti-EV 1-5, anti-EV 1-1 or EV2-1, or anti-Epo receptor (EpoR), anti-EPHB 4, anti-CSF 2RB, antisense oligonucleotide, DNA decoy, RNA decoy, ribozyme, antagomiR, shRNA, LNA or siRNA. Several uses of these modulators of function have been described, which have been advantageously used as medicaments and for the treatment of tumour pathologies, proliferative pathologies, autoimmune and non-autoimmune chronic inflammatory diseases, for the treatment of neurodegenerative diseases and for the treatment of patients undergoing organ or tissue transplantation. The invention also describes variants of EPO for use in the diagnosis and treatment of tumor pathologies, proliferative pathologies, autoimmune and non-autoimmune chronic inflammatory diseases, in the diagnosis and treatment of neurodegenerative diseases, and in the treatment of patients undergoing organ or tissue transplantation and as diagnostic agents. According to another aspect, monoclonal antibodies to at least one variant of erythropoietin are described. According to another aspect, the use of at least one alternative splice variant of non-erythrogenic EPO and its measurement at the tissue and/or system level, as well as the study of the methylation status of the promoters of genes involved in the EPO signaling pathway (e.g. EPO, EPOR, EPHB, CSF2 RB) as diagnostic, prognostic and predictive markers for oncological, proliferative, neurodegenerative or inflammatory pathologies are described.
Achilles tendon rupture (ATR) is commonly treated with open surgical repair. Following surgical repair, there are a variety of protocols, ranging from complete immobilization to immediate postoperative mobilization with early weightbearing. However, no clear consensus regarding the optimal postoperative rehabilitation protocol for ATRs exists. Early rehabilitation after ATR has been shown to be beneficial in animal and human studies. Human prospective studies and randomized controlled trials have shown that early postoperative mobilization do not pose additional risks compared to cast immobilization, with a trend toward a reduction in lost work days and an earlier return to sport. However, these trials define early postoperative mobilization differently (i.e. use different combinations of weightbearing and range of motion). This makes it difficult to determine which factor in the early rehabilitation process plays an important role in optimizing recovery. An important component of early rehabilitation is weightbearing.

Comparison: Patients weightbearing in the early rehabilitation period after surgical repair of the Achilles tendon compared to patients non-weightbearing after the surgical repair of the Achilles tendon repair. With the exception of weightbearing status, both groups performed the same rehabilitation program.
BACKGRUOUND: Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.
METHODS: We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.
RESULTS: Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin.
CONCLUSION: We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.
INTRODUCTION: Prenatal exposure to nonpersistent chemicals, including organophosphate pesticides, phthalates, and bisphenols, is associated with altered fetal and childhood growth. Few studies have examined these associations using longitudinal growth trajectories or considering exposure to chemical mixtures.
METHODS: Among 777 participants from the Generation R Study, we used growth mixture models to identify weight and body mass index trajectories using weight and height measures collected from the prenatal period to age 13. We measured exposure biomarkers for organophosphate pesticides, phthalates, and bisphenols in maternal urine at three timepoints during pregnancy. Multinomial logistic regression was used to estimate associations between averaged exposure biomarker concentrations and growth trajectories. We used quantile g-computation to estimate joint associations with growth trajectories.
RESULTS: Phthalic acid (OR = 1.4; 95% CI = 1.01, 1.9) and bisphenol A (OR = 1.5; 95% CI = 1.0, 2.2) were associated with higher odds of a growth trajectory characterized by smaller prenatal and larger childhood weight relative to a referent trajectory of larger prenatal and average childhood weight. Biomarkers of organophosphate pesticides, individually and jointly, were associated with lower odds of a growth trajectory characterized by average prenatal and lower childhood weight.
CONCLUSIONS: Exposure to phthalates and bisphenol A was positively associated with a weight trajectory characterized by lower prenatal and higher childhood weight, while exposure to organophosphate pesticides was negatively associated with a trajectory of average prenatal and lower childhood weight. This study is consistent with the hypothesis that nonpersistent chemical exposures disrupt growth trajectories from the prenatal period through childhood.
Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated in vivo through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, in vivo knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.
Docetaxel will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
Endometrial cancer was diagnosed with histopathological examination of the samples obtained by dilatation and curettage. Preoperative serum CA-125 levels were determined in all patients. Serum and abdominal washing fluid CA-125 levels were measured with a double antibody sandwich immunoenzymatic method, using Beckman Coulter DXI (Ireland) analyzer. In addition to routine preoperative investigations, MRI was done in patients who were thought to have an extension outside the uterus.

During surgery, abdominal exploration was performed first, and then an abdominal fluid sample was obtained for cytological examination and measurement of CA-125 level. One hundred milliliters of normal saline was used as the abdominal washing liquid to obtain the sample for CA-125 measurement. Subsequently, total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO) were performed.
Lotrafilcon B commercially marketed contact lens randomly assigned to one eye, with galyfilcon A commercially marketed contact lens in the fellow eye for contralateral wear. Lenses were worn for approximately 5 days or more per week, at least 10 hours per day, for up to 4 weeks in a daily wear (DW modality).
BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a rare leukemia subtype first classified by the World Health Organization in 2016. The incidence of Ph+ AML is approximately 0.5 - 3%, and its prognosis is poor. Ph+ AML with additional chromosomal abnormalities in children has rarely been reported, and its treatment and prognosis remain uncertain.
METHODS: We retrospectively analyzed 649 patients with AML from 2006 - 2021. Six (0.9%) patients with Ph+ AML were identified and treated with conventional chemotherapy. The clinical features and prognoses were retrospectively analyzed.
RESULTS: Six cases of AML with a Ph chromosome were reported. One of the six individuals exhibited a biphenotypic immunophenotype, one exhibited a simple myeloid immunophenotype, and the other four exhibited myeloid and lymphoid expression. Karyotypic analysis (R banding) was performed in six cases, four of which were classical Ph chromosomal abnormalities, two of which had additional abnormalities outside the Ph chromosome. Fluorescence in situ hybridization (FISH) analysis using the BCR/ABL fusion gene distinguished that the BCR major breakpoint break in three cases was type P210 and the BCR minor breakpoint break in three cases was type P190. The complete remission rate of the six patients in this study using conventional chemotherapy was 60%, with a median survival time of 7.5 months.
CONCLUSIONS: In summary, Ph+ AML is a heterogeneous disease often associated with additional chromosomal abnormalities. Ph+ AML is seen with a lymphoid immunophenotype and alterations in associated genes such as the IGH gene. Adults were predominantly P210 and two cases in children were both P190. Conventional treatments are less effective, and there are no standard treatment regimens.
This is a randomised, double-blind, placebo-controlled, two-period crossover proof-of-concept trial of methylphenidate (MPH) for children with childhood apraxia of speech (CAS). 24 children aged 6 to 12 years with CAS will be recruited. If children pass the screening procedure, which includes a physical exam conducted by a medical officer at the Melbourne Children's Campus, children will be enrolled into the 8 weeks + 2-day trial (includes 2-day washout). Participants will be randomly assigned to sequence A (4 weeks of MPH, followed by 4 weeks of placebo) or sequence B (4 weeks of placebo, followed by 4 weeks of MPH). After 4 weeks in period 1, a two-day washout period will occur before participants crossover to period 2 for 4 weeks. Pre- and post-treatment speech outcomes will be measured. The investigators' primary objective is to provide proof-of-concept that speech intelligibility could demonstrate greater improvements from baseline to 4 weeks following a 4-week period of MPH use compared with placebo in children with CAS. The secondary objectives are to describe feasibility, tolerability and change from baseline in: connected speech intelligibility, quality of language production, speech quality, functional speech intelligibility, phonological working memory, attentional and hyperactive behaviour.
Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including melphalan). Some patients also received other chemotherapeutic agents or radiation therapy. Precise quantitation of the risk of acute leukemia, myeloproliferative syndrome, or carcinoma is not possible. Published reports of leukemia in patients who have received melphalan (and other alkylating agents) suggest that the risk of leukemogenesis increases with chronicity of treatment and with cumulative dose. In one study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was 19.5% for cumulative doses ranging from 730 to 9,652 mg. In this same study, as well as in an additional study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was less than 2% for cumulative doses under 600 mg. This does not mean that there is a cumulative dose below which there is no risk of the induction of secondary malignancy. The potential benefits from melphalan therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.

Adequate and well-controlled carcinogenicity studies have not been conducted in animals. However, intraperitoneal (IP) administration of melphalan in rats (5.4 to 10.8 mg/m2) and in mice (2.25 to 4.5 mg/m2) 3 times per week for 6 months followed by 12 months post-dose observation produced peritoneal sarcoma and lung tumors, respectively.
PURPOSE:The titled emulsion, obtained by adding a substance reactive with iron ions to blacken and an aqueous solution of soap to an aqueous solution of a water-soluble inorganic iron salt, and adding a thickener or alcohol thereto, and capabler of blackening gray hair into black hair unfadable even after washing the hair by very easy operation. CONSTITUTION:A hairdressing emulsion obtained by adding a substane reactive with iron ions, e.g. gallic acid, tannic acid, pyrogallol, dopa or phloroglucinol, to blacken and an aqueous solution of soap to an aqueous solution of a water- soluble inorganic iron salt, e.g. ferrous sulfate or ferric chloride, to form a black dyestuff in a state of dispersion in water, adding a thickener, e.g. high polymer saccharide or sodium carboxymethyl cellulose (CMC-Na), for preventing settling of the above-mentioned dyestuff and an alcohol for uniforming the product thereto, and further adding if necessary a preservative, perfume, etc. thereto. The above-mentioned emulsion is applied to the hair to exhibit good dyeing property, and the color is scarcely removed even by washing the hair with an acidic shampoo.
Eligible subjects will first enter Arm A1, receive treatment for this group on D1, and undergo study visits and biological sample collection (PK samples and immunogenicity samples) at established timepoints. After the last subject in Arm A1 has completed at least 3 days of safety and tolerability observation,After no safety events (≥ Grade 2 study drug-related AEs) have occurred as assessed by the investigator, enrollment into the A2 Arm may be initiated. Enrollment in subsequent treatment groups and so on. If a subject in this dose group experiences an AE ≥ Grade 2 related to the investigational product, the investigator will assess the time to continue observation and start the next treatment group according to the subject ' s condition.

Based on the data obtained in Phase 1b, the grouping for Phase 2 will be determined by the investigator and the sponsor in consultation. It may be Group X1, Group X2, and Group X3. Eligible subjects were randomized 1: 1: 1: 1 to receive treatment in Group X1, X2, X3, or placebo on D1 and to undergo study visits and biological sample collection (immunogenicity samples) at established timepoints.
Control group Trabectedin 1.3 mg/m\^2 i.v.will be administered on Day 1. Dexamethasone will be administered 30 minutes prior to trabectedin.
PURPOSE:To improve the adhesiveness for skin by allowing an adhesive layer to contain the adhesiveness applying resin. CONSTITUTION:The hydrophilic polymer used for adhesive composition comprises at least one kind selected from the group consisting of (cross-linked type) polyacrylic acid (salt), carboxymethyl-cellulose (salt), hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, sodium alginate, polyvinyl pyrrolidone, methyl vinyl ether - maleic anhydride copolymer and gelatin. Water is used in 200-1200 pts.wt. for 100 pts.wt. hydrophilic polymer. The adhesiveness applying resin consists of at least one kind selected from the group consisting of rosin ester, hydrogen-added petroleum resin, and terpene group resin, and incorporated with 10-300 pts.wt. for 100 pts.wt. of hydrophilic polymer. Accordingly, the excellent adhesiveness for skin can be obtained.
The present invention provides a partial cDNA corresponding to an RNA containing double stranded regions (R-RNA), which, when transcribed in vitro, gives rise to an RNA transcript that activates PKR. An approximately 226-252 bp nucleotide (nt) sequence responsible for activation of PKR (the activation sequence) has been identified within the cDNA and isolated. Antisense oligonucleotides corresponding to specific portions of the 252 nt cDNA fragment stimulate proliferation of different cells in culture. Various portions of the cDNA or R-RNA may also be used to inhibit cell proliferation in cell cultures. The present invention further provides pharmaceutical compositions comprising the subject nucleic acid fragments and oligonucleotides. Kits which comprise at least one of the subject isolated nucleic acid molecules or oligonucleotides and a pharmaceutically acceptable carrier are also provided.
Ovarian endometrioma (OE) is a common gynecological condition characterized by the formation of "chocolate cysts". Recent research indicates that the cyst fluid acts as a "toxic environment" for the ovary and plays a significant role in the development of OE, with macrophages being pivotal. However, the specific molecular and cellular mechanisms of it are not fully understood. In this study, clinical samples are integrated, single-cell sequencing, in vivo and in vitro experimental models to comprehensively investigate the effects of OE fluid on ovarian function and the mechanisms of it. Combined with bioinformatics analysis and experimental validation, the findings demonstrate that OE fluid can cause ovarian function decline, which associated with inflammatory response, and mitochondrial dysfunction and cellular senescence, while activating the cGAS/STING signaling pathway. As a STING inhibitor, H-151 effectively alleviates ovarian dysfunction, inflammatory state and cell apoptosis induced by OE fluid. Furthermore, it is also discovered that H-151 can inhibit OE fluid-induced mitochondrial dysfunction and cellular senescence. These findings provide important theoretical and experimental foundations for further research and development of STING inhibitors as potential drugs for treating ovarian dysfunction.
The invention relates to an innovative form of antiedematous substance application, in a form of plasters, comprising aluminum acetate-tartrate. 
     Apart from aluminum acetate-tartrate (or another substance mentioned above), the plaster can comprise one or few other active substances having an adjunctive or enhancing effect with respect to aluminum acetate-tartrate. The plaster structure is based on a possibility of storing and controlled release of the biologically active substances. The active substances, depending to the plaster structure, may be subject to the modified (e.g. sustained) release. Therapeutic properties of the product result from the combination of all constituents of the given product. Analysis has also shown a synergistic effect.
Surgery will be performed by a certified trauma surgeon, with experience in wrist arthroscopy. A delay of minimal 5 days before performing arthroscopy is mandatory to enable visualisation due to the organisation of the hematoma. During wrist arthroscopy, the forearm will be positioned upright and in neutral position, the elbow flexed by 90° and axial traction of 4-6 kg will be performed. Four portal entrees are created by superficial stab incisions and blunt preparation through the joint capsule; one midcarpal radiair and one midcarpal ulnar portal and the 3-4 and 6-R portal. A shaver is used for removal of fracture haematoma and osteocartilaginous debris. Cartilage damage will be graded using the Outerbridge classification system. With the 1 mm hook probe assessment of the quality of reduction and ligamentous injuries (TFCC, scapholunate and lunotriquetral) will be performed. Wound closure will be performed using standard techniques.