anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cancer cells exhibit significant alterations in their metabolism, characterised by a reduction in oxidative phosphorylation (OXPHOS) and an increased reliance on glycolysis, even in the presence of oxygen. This metabolic shift, known as the Warburg effect, is pivotal in fuelling cancer's uncontrolled growth, invasion, and therapeutic resistance. While dysregulation of many genes contributes to this metabolic shift, the tumour suppressor gene p53 emerges as a master player. Yet, the molecular mechanisms remain elusive. This study introduces a comprehensive mathematical model, integrating essential p53 targets, offering insights into how p53 orchestrates its targets to redirect cancer metabolism towards an OXPHOS-dominant state. Simulation outcomes align closely with experimental data comparing glucose metabolism in colon cancer cells with wild-type and mutated p53. Additionally, our findings reveal the dynamic capability of elevated p53 activation to fully reverse the Warburg effect, highlighting the significance of its activity levels not just in triggering apoptosis (programmed cell death) post-chemotherapy but also in modifying the metabolic pathways implicated in treatment resistance. In scenarios of p53 mutations, our analysis suggests targeting glycolysis-instigating signalling pathways as an alternative strategy, whereas targeting solely synthesis of cytochrome c oxidase 2 (SCO2) does support mitochondrial respiration but may not effectively suppress the glycolysis pathway, potentially boosting the energy production and cancer cell viability.
Patients between the ages of 5-18 years. They will complete the 5-18 version of the BOQ on iPads or through the HTTPS Tonic link.
Older diabetes patients will attend regular clinician visits and one targeted primary care physician visit during the 12 weeks post-enrollment. They will be enrolled in a diabetes education class. Blood pressure, H1C and lipids will be measured at enrollment, 6 weeks , and 12 weeks.
PURPOSE:To obtain a formed hydrophobic gel of KONJAK (paste made from starch of devil's tongue) or gelatinous substance of formed hydrophobic KONJAK having high strength, by forming a mixture of hydrophilic KONJAK derivative,a catalyst and optionally other substances and heat-treating the formed mixture at a specific temperature. CONSTITUTION:A mixture of (A) a hydrophilic KONJAK derivative giving hydrophobic KONJAK by freezing and (B) a catalyst (preferably hydrochloric acid, adipic acid, anhydrous ethanol, etc.) or a mixture of the above components and (C) other substances (preferably cereals, synthetic resins, etc.) is formed and heat-treated at >=80 deg.C. The formed mixture may be frozen in place of heat-treatment. EFFECT:A KONJAK derivative can be utilized in various uses by the thermal gelatinization.
Basal cell carcinomas (BCCs) are a common skin problem largely caused by long term sun exposure. Current treatments include surgery, curettage/desiccation and simple excision, which are often cosmetically disfiguring. Non-invasive alternative therapy for treatment of BCC lesions is thus being researched. Sap from the plant Euphorbia peplus has been used for many years in Australia as a "folk" remedy to treat a number of skin conditions. The active component of Euphorbia peplus has been isolated and made into a gel applied directly to the skin by Peplin Ltd. To date, only one well-controlled study with PEP005 gel in humans has been completed. Sixteen patients received a single application of PEP005 0.01% or vehicle gel to actinic keratoses on the chest, shoulders, back and/or arms. Results show good tolerance and evidence of activity. The current study is designed to evaluate the safety of two applications of PEP005 gel in patients with superficial basal cell carcinoma (sBCC) on the arms, shoulders, chest, face and/or scalp, testing three concentrations according to two treatment regimens. Approximately 60 patients are planned to be included from multiple Australian centers. Efficacy and cosmetic outcome will be assessed and a recommended treatment regimen will be determined. Assignment to treatment is random and patients and medical staff will be blinded as to the treatment. Patients will have two visits for treatment application and will return for check-up visits the day after the first application and several times thereafter for approximately 3 months.
In Part 1, participants will receive one injection (administration of open-label placebo injections without any active ingredient (5 ml 0.9% saline)) at twenty minutes after start of the experiment during the intervention visit 2. Visit 1 (No treatment) will be the control of the study intervention.
The invention discloses a construction method and application for a double micro-molecule disturbance RNA carrier. It includes the following steps: compounding construction primer of double siRNA producing carrier, PCR expanding of siRNA producing module; cloning and sequencing. The invention has the advantages of simple method to construct siRNA carrier, convenient to operate, and high RNA disturbance efficiency. It could make the gene expression that has the same source sequence of siRNA dumbness and would not influence to other functions of the gene. It has strong specificity, and no poison function. It is a good method to cure virus mixed infection by the double siRNA.
A body implantable lead for the delivery of stimulation energy to a desired body site including a drug dispenser carried by the lead which retains a drug to be dispensed while allowing a dispensing of that drug at least adjacent the desired body stimulation site. The drug may be one which is intended to counter thrombus formation, fibrosis, inflammation or arrhythmias, or any combination thereof, or to accomplish any other localized purpose. The drug may be in liquid form retained in a reservoir carried by the lead with an agency controlling dispensing of the drug. The controlling agency may be a semi-permeable membrane. Alternatively, the reservoir may be formed as an osmotic pump. As a further alternative, the drug may be retained as a coating on a large surface area portion of the lead, or an electrode carried by the lead. In a preferred embodiment, the drug is compounded into a solid material which is carried by the lead while being exposed to body tissues and flesh or fluids at least adjacent the desired stimulation site.
PG positive (PGⅠ ≤ 70ng/ml and PGⅠ/PGⅡ≤7.0) and Hp negative. A questionnaire survey are accomplished in 40-70 years old candidates. Eligible subjects are detected PG I and II, Hp-IgG antibody through serological examination. Gastroscope also accomplished in all participants.
The adjuvant treatment of resected pancreatic cancer is currently in flux. Many in the United States continue to use 5FU-based chemotherapy with radiation to the pancreatic bed. Some in the States, and most investigators in Europe, use a 5FU based chemotherapy-alone approach, based on the ESPAC-1 data. Many investigators believe that since gemcitabine is a more active drug in the metastatic setting, it should be moved "up front" in the adjuvant treatment of pancreatic cancer patients. At Columbia, we offer gemcitabine-based treatments with discussions with patients regarding risks, benefits, and limitations in current knowledge. We have usually offered radiation to those with positive margins, and chemotherapy alone to those without. Based on the early studies using gemcitabine, we believe that this will ultimately prove to be a more effective adjuvant drug than 5FU. Some patients have asked for GTX in the adjuvant setting as well, prompting the creation of this trial. Because of concerns about increased toxicity of this regimen, determination of patient safety will be the primary objective of this study, through careful monitoring of adverse events. This trial will be a chemotherapy-only study, offered to those with clean margins of resection.

Taxotere administered "weekly" has activity in a variety of tumor types including breast, lung, ovarian and prostate cancer. Patients with advanced breast cancer, including some who had previously been treated with paclitaxel or anthracyclines, have responded to the weekly administration of Taxotere. The recommended dose of weekly Taxotere is 30-40 mg/m2/week for 6 out of 8 weeks. The same dose intensity can be achieved on a 3 out of 4 week basis. However, this protocol will give drugs 2 out of every 3 weeks, thus dose intensity is less.

Weekly administration of Taxotere is well tolerated and produces substantially less myelosuppression than is observed with standard Taxotere administration every 3 weeks. Acute toxicities are uncommon, as is peripheral neuropathy. Prolonged treatment with weekly Taxotere, may result in chronic toxicities (including, asthenia (fatigue), anemia, edema, excessive lacrimation (epiphora), and onycholysis). Chronic toxicities are most prominent when Taxotere is administered on a continuous weekly basis, i.e., without a break, and are delayed in onset by providing breaks in treatment (for example, treating 6 out of 8 weeks or 3 out of 4 weeks); these chronic toxicities occur at a lower cumulative dose when a continuous weekly schedule of Taxotere is utilized.

Premedication with dexamethasone is recommended for all patients receiving weekly Taxotere therapy to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. A variety of dexamethasone schedules have been used in studies with weekly Taxotere. Dexamethasone 4 to 8 mg x 3 doses taken orally the night before, the morning of, and the evening after Taxotere administration appears to be an effective schedule. We have found that a single low dose of 10 mg IV before the Taxotere usually prevents anaphylaxis and the pedal edema associated with this drug.
This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches(assessed at Session P2). They will continue to receive only nicotine patches.
Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. In vitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied. Utilizing targeted next-generation sequencing, we screened for genetic polymorphisms covering the colistin transporters (SLC15A1, SLC15A2, SLC22A5, LRP2, and ABCB1) in 42 critically ill patients who received colistimethate sodium. The genetic variants rs2257212 ((NM_021082.4):c.1048C>G) and rs13397109 ((NM_004525.3):C.7626C > T) were identified as being associated with an increased incidence of acute kidney injury (AKI) on Day 7. Colistin area under the curve (AUC) was predicted using a previously published pharmacokinetic model of colistin. Using logistic regression analysis, the predicted 24-h AUC of colistin was identified as an important contributor for increased odds of AKI on Day 7. Among 42 patients, 4 (9.5%) were identified as having high predisposition to colistin-induced AKI based on the presence of predisposing genetic variants. Determination of the presence of the abovementioned genetic variants and early therapeutic drug monitoring may reduce or prevent colistin-induced nephrotoxicity and facilitate dose optimization of colistimethate sodium.
Process for forming a dispersion of spherules comprising organised molecular layers contg. an encapsulated aqueous phase comprises (a) mixing (i) a water-dispersible, liq. lipid having a nonionic or ionic hydrophilic portion and a lipophilic portion adn of HLB value such that it swells in the encapsulated aqs. phase, ith (ii) the aqueous phase to be encapsulated; (b) stirring to form a lamellar phase; and (c) addig a dispersing liq. in amt. greater than that of the lamellar phase and vigorously shaking for 15 min. to 3 hrs. Process is esp. used for encapsulation of cosmetic agents such as artificial tanning agents, sunscreen agents, antiperspirants, deodorants, depilatories, antiserborrhoeics etc., or a foodstuff or pharmaceutical agent such as vitamins, hormones, enzymes, vaccines, antiinflammatories, e.g. hydrocortisone, antibiotics and bactericides.
The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise.
The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.
Ganaxolone has potential for abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. In a human abuse potential study, 400, 800, and 2000 mg oral doses of ZTALMY were compared to a 6 mg oral dose of lorazepam and placebo. On positive subjective measures of "drug liking", "overall drug liking", "high", "good drug effects", and "take drug again", the 400 and 800 mg doses of ZTALMY produced mean scores that were within or just outside of the acceptable placebo range and were not statistically significantly different than placebo. The 2000 mg dose of ZTALMY produced responses on these positive subjective measures that were slightly greater than the acceptable placebo range and were statistically significantly greater than placebo. Scores on these positive subjective measures for all three doses of ZTALMY were statistically significantly lower than those produced by lorazepam.
Drug delivery system comprises a certain number of hormone-containing daily unit, which exhibits a hormone combination consisting of at least an estrogen from ethinyl estradiol (I) and estradiol (II) and from at least a metabolite of the chlormadinone acetate from e.g. 3alpha -hydroxy-6-chloro-17alpha -acetoxy-4,6-pregnadiene-20-one, optionally mixed with chlormadinone acetate as gestagen component for the continuous, daily, oral administration of the hormone-containing daily units, optionally in combination with 7 to 3 hormone-free daily units for the hormonal contraception. Drug delivery system for the hormonal contraception comprises a certain number of hormone-containing daily units, which exhibits a hormone combination consisting of at least an estrogen from ethinyl estradiol (I) and estradiol (II) as estrogen components and from at least a metabolite of the chlormadinone acetate from 3alpha -hydroxy-6-chloro-17alpha -acetoxy-4,6-pregnadiene-20-one (3alpha -hydroxy-chlormadinone acetate), 3beta -hydroxy-6-chloro-17alpha -acetoxy-4,6-pregnadiene-20-one (3beta -hydroxy-chlormadinone acetate), optionally mixed with chlormadinone acetate and/or 3alpha -hydroxy-6-chloro-17alpha -acetoxy-5beta -pregnane-20-one and/or 3beta -hydroxy-17alpha -acetoxy-5beta -pregnane-20-one as gestagen component for the continuous, daily, oral administration of the hormone-containing daily units, optionally in combination with 7 to 3 hormone-free daily units. Independent claims are included for: (1) a kit comprising at least a drug delivery system for the hormonal contraception; and (2) a kit comprising several drug delivery systems. ACTIVITY : Contraceptive; Neuroprotective. MECHANISM OF ACTION : None given.
Improvements in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatments in the United States have made the disease in many cases a chronic illness. However, many individuals have failed multiple lines of standard therapy, and thus, development of new modes of salvage treatment is crucial. Restriction of viral replication, mediated by CD8+ cells, appears to play an important role in control of HIV replication. A subset of individuals, many of whom possess human leukocyte antigen (HLA) B\*57 exhibit restriction of HIV type 1 viral replication to less than 50 copies/mL, presumably by a mechanism that is CD8+ T-cell mediated, and become elite long-term non-progressors (LTNP), who have no evidence of progressive immunodeficiency and no development of opportunistic complications during many years of follow-up. Other individuals, including those with HLA-B\*57 show no evidence of control of HIV replication, and without antiretroviral therapy will develop progressive immunodeficiency and HIV-related opportunistic complications. In this exploratory study, we are investigating a novel cell transfer strategy: up to 3 patients with HIV infection have failed at least 2 standard regimens of antiretroviral therapy, have a CD4+ count under 200 cells/mm (3), and a plasma HIV viral load of greater than 10,000 copies/mL, will be administered 10 (10) peripheral blood mononuclear cells obtained by lymphapheresis from an "elite" LTNP matched to the recipient on at least one HLA-B allele. Up to 70 patients may be enrolled for screening to identify 3 donors and 3 recipients. Up to 3 infusions may be administered per patient, with each infusion occurring no more frequently than every 3 months. The primary endpoints will be the safety of the infusions and the survival of donor cells in the recipient. Changes in the recipient s CD4+ and CD8+ cell number, other immune parameters, and plasma HIV viral load will also be monitored closely for evidence of anti-HIV activity.
Extended suicide, a specific type of homicide-suicide event, has severe social consequences yet remains lacking systematic research. This retrospective study investigated 51 cases of extended suicide involving mental disorders in central China with aim of better understanding risk factors for such events and guiding prevention strategies. Over an 8-year period from 2015 to 2022, cases were collected from forensic institutions, and demographic characteristics, case details, and psychiatric data were recorded. The 51 incidents involved 51 perpetrators and 79 victims, with more female perpetrators (58.8%) and more female victims (54.4%). The average age of the perpetrators was 36.1, and most were married (88.2%). Almost all of the victims were family members of the perpetrator, like the most numerous children (64.6%), followed by spouses (24.1%). The most common homicide mode of death was mechanical asphyxia (38.0%), followed by sharp devices (36.7%) and drug poisoning (16.5%). Depressive disorders (76.5%) were the most common diagnosis of mental disorder for perpetrators. The study analyzed the unique characteristics of extended suicide to enrich such data. These findings help strengthen the screening and identification of potential perpetrators and victims to prevent such cases from occurring.
Nephrotic syndrome (NS) is characterized by proteinuria and hypoalbuminemia, and patients with nephrotic syndrome are known to be hypercoaguable with increased incidence of venous thromboembolism necessitating anticoagulation. While classically warfarin has been used as an anticoagulant in NS, newer oral anticoagulants, such as apixaban, are increasingly used to treat venous thromboembolism (VTE) in the general population. It is unknown how hypoalbuminemia and proteinuria affect the pharmacokinetics and pharmacodynamics of apixaban.

This will be a parallel arm, single-dose pilot study of the pharmacokinetics of apixaban in adults with nephrotic syndrome. Goal enrollment of twenty subjects with non-diabetic nephropathy who have nephrotic-range proteinuria, defined as \>3.5g/24 hours or UPC \>3.5 and ten healthy control subjects without nephrotic syndrome. Each subject will be administered a single dose of apixaban 10 mg. Plasma drug concentration level and plasma anti-Xa activity levels will be measured at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration in order to determine the maximum plasma concentration of apixaban, area under the curve, and half-life of apixaban in the setting of hypoalbuminemia and proteinuria due to nephrotic syndrome. Apixaban levels will be measured via liquid-chromatography spectrometry mass. Additionally, thrombin generation will be measured at 0, 3, 6, and 24 hours.