anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVES: Routine screening for chronic kidney disease (CKD) could enable timely interventions to slow down disease progression, but currently there are no clinical guidelines for screening. We aim to evaluate the cost-effectiveness of screening for CKD using a novel analytical tool based on a cumulative sum statistic of estimated glomerular filtration rate (CUSUMGFR).
METHODS: We developed a microsimulation model that captured CKD disease progression, major complications, patients' awareness, and treatment adherence for a nationally representative synthetic cohort of age ≥ 30 years in the United States. In addition to the status quo with no screening, we considered four CUSUMGFR-based universal screening policies by frequency (annual or biennial) and starting age (30 or 60 years), and two targeted annual screening policies for patients with hypertension and diabetes, respectively. For each policy, we evaluated the total discounted disability-adjusted life years (DALYs) and direct health costs over a lifetime horizon and estimated the incremental cost-effectiveness ratio (ICER). We further performed one-way and probabilistic sensitivity analyses to assess the impact of parameter uncertainty.
RESULTS: Compared with the status quo, all the CUSUMGFR-based screening policies were cost-effective under the willingness-to-pay (WTP) range of $50,000 -$100,000, with the estimated incremental cost-effectiveness ratios (ICERs) ranging from $15,614/DALYs averted to $54,373/DALYs averted. Universal annual screening with starting age of 30 was the non-dominated policy on the cost-effectiveness frontier under the WTP of approximately $25,000. Adding more recent treatment option of sodium-glucose cotransporter-2 (SGLT2) inhibitors to the treatment regimen was found to be cost-saving. Among the most influential model parameters, variation in the CKD progression rate, adherence, and testing cost resulted in the highest variability in model outcomes.
CONCLUSIONS: CUSUMGFR-based screening policies for CKD are highly cost-effective in identifying patients at risk of end stage kidney disease in early stages of CKD. Given its simple requirement of a basic blood test, the CUSUMGFR-based screening can be easily incorporated into clinical workflow for disease monitoring and prevention.
Aberrant expression of G protein-coupled receptor class C group 5 member A (GPRC5A) has been reported in multiple cancers and is closely related to patient prognosis. However, the mechanistic role of GPRC5A in gallbladder cancer (GBC) remains unclear. Here, we determined tumor expression levels of GPRC5A and the molecular mechanisms by which GPRC5A regulates gallbladder cancer metastasis. We found that GPRC5A was significantly upregulated in GBC, correlating with poorer patient survival. Knocking down GPRC5A inhibited GBC cell metastasis both in vitro and in vivo. GRPRC5A knockdown resulted in downregulation of TNS4 expression through the JAK2-STAT3 axis. Clinically, GPRC5A expression positively correlated with TNS4. Finally, STAT3 bound to TNS4's promoter region, inducing its expression. Overall, GPRC5A showed high expression in GBC tissues, associated with poor patient prognosis. Our findings first demonstrate that the GPRC5A-JAK2-STAT3-TNS4 pathway promotes GBC cell metastasis, suggesting potential therapy targets.
It has been discovered that proliferation of inflammatory breast cancer (IBC) cells can be inhibited by inhibiting the function of histone deacetylase 6 (HDAC6). Advantageously, such functional inhibition is accomplished by administration of a therapeutically effective dose of Ricolinostat (ACY1215) to a patient in whom IBC cells are proliferating. In further accordance with the invention, it is possible to predict the responsiveness of a particular patient with cancer (particularly breast cancer, and most specifically inflammatory breast cancer) to administration of an HDSC6 inhibitor. This is accomplished by acquiring mRNA gene expression profiles of a biopsy sample of the patient's tumor tissue. The processed gene expression profiles of the patient are then integrated into a gene expression database and are then normalized across the entire database. Then, the normalized gene expression profiles are input to an algorithm. An HDAC6 signature characteristic of the patient's tumor type is also input to the algorithm, and the output of the algorithm makes it possible to evaluate the responsiveness of the patient's tumor to administration of HDAC6 inhibitor. Advantageously, the gene expression profiles are acquired using standard RNA-Seq technology or microarray and the gene expression database is The Cancer Genome Atlas ("TCGA").
FIELD: medicine, toxicology. SUBSTANCE: method is based on saturation of organs and tissues microcirculation with oxygen. For this purpose perfluorocarbon emulsion perfluoran is administrated parenterally twice, each other day at the dose 6-12 ml/kg after poisoning. Method ensures to enhance the effectiveness of treatment of toxic body damage by saturation of microcirculatory stream with oxygen and penetration into contracted and spasmodic vessels due to decreased emulsion particles. EFFECT: enhanced effectiveness of treatment. 3 tbl
Epidemiological data indicate a strong association between alcohol use disorder (AUD) and neuropathic pain. Genetically-selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit a high preference for alcohol compared with their background strain (Wistar rats), but their sensitivity to mechanical allodynia after chronic alcohol exposure is unknown. The present study compared the development of mechanical allodynia between "low, non-pathological drinker" Wistar rats and "high drinker" msP rats using the two-bottle choice (2BC) free-access procedure. Several studies reported the involvement of endocannabinoids (eCBs) in modulating mechanical allodynia, but there are no data on their role in alcohol-related allodynia. Thus, the present study assessed eCBs and their related lipid species in lumbar dorsal root ganglia (DRG) and correlated them with mechanical allodynia in our model. We found that male and female msP rats developed persistent mechanical allodynia during protracted abstinence from alcohol, presenting no sign of recovery, as opposed to Wistar rats. This effect directly correlated with their total alcohol intake. Notably, we found a correlation between lower lumbar DRG 2-arachidonoylglycerol (2-AG) levels and the development of higher mechanical allodynia during abstinence in msP rats of both sexes but not in Wistar rats. Moreover, alcohol-exposed and abstinent msP and Wistar females but not males exhibited significant alterations of thromboxane B2 and prostaglandin E2/prostaglandin D2 compared with naive rats. These findings demonstrate that DRG 2-AG metabolism is altered in msP rats during prolonged abstinence and represents a potentially interesting pharmacological target for the treatment of mechanical allodynia during alcohol abstinence.
OBJECTIVE: To investigate the clinical efficacy of transumbilical single-incision laparoscopic surgery in the treatment of complicated appendicitis in overweight/obese adolescents.
METHODS: A retrospective analysis was conducted on the clinical data of 226 adolescent patients with complicated appendicitis who were admitted to our hospital from January 2014 to June 2022. Among them, 102 cases underwent transumbilical single-incision laparoscopic appendectomy as the observation group, and another 124 cases underwent conventional three-port laparoscopic appendectomy as the control group. The surgical time, intraoperative blood loss, duration of incisional pain, postoperative flatus time, length of hospital stay, surgical site infection (SSI), satisfaction with cosmetic result, and occurrence of postoperative complications were compared between the two groups.
RESULTS: Both groups completed the surgery smoothly, and there were no statistically significant differences in gender, age, BMI, duration of illness, white blood cell count, and preoperative CRP value between the two groups (P > 0.05). There were no statistically significant differences in surgical time and intraoperative blood loss between the two groups (P > 0.05). However, the observation group had shorter hospital stays, shorter duration of incisional pain, shorter postoperative time to flatus, and lower overall postoperative complication rates compared to the control group, with statistically significant differences (P < 0.05). The observation group had higher satisfaction with cosmetic result compared to the control group, with statistically significant differences (P < 0.05). Both groups were followed up for one year postoperatively, and there were no occurrences of residual appendicitis or severe adhesive intestinal obstruction.
CONCLUSION: When proficiently mastered, the application of transumbilical single-incision laparoscopy in the treatment of complicated appendicitis in overweight/obese adolescents offers advantages such as minimal trauma, rapid recovery, fewer complications, and improved aesthetic outcomes.
FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, and is intended for treatment of Helicobacter pylori (HP) associated chronic ulcerous disease of stomach and duodenum. Carried out is drug therapy, which includes per-oral introduction of sub-citrate of bismuth, omeprazole, amoxicillin and furazolidone, immune-modulator of microbial origin and complex bifido and lacto bacteria. As immuno-modulator of microbial origin introduced is ribomunyl. Dose is 750 mg. During the first month 1 time per day in the morning on an empty stomach on the first 4 days of each week. In the following 2 months -the first 4 days of each month. Complex bifido and lacto bacteria (LB-complex) in dose 5 ml, during 25 days from the first day of antibacterial medication intake. Intake is before 30 minutes before a meal. Content of microbial bodies in 1 ml of complex is 1010-1012. ^ EFFECT: method makes it possible to correct secondary immunodeficiency and reduce treatment terms. ^ 3 cl, 2 dwg, 2 ex
The INSURE trial is a multi-center, prospective trial to collect information about adequate ICD therapies in ICD patients before \& after their first elective ICD replacement. For this purpose all consecutive ICD patients will be included in the study, whose first implanted device is replaced due to ICD battery depletion (i.e. arrival at battery indicator ERI). ICD replacements due to other reasons can be included if duration of first ICD implantation was \> 3 years. All patients included in the trial are regularly followed up until delivery of their first adequate ICD therapy. The collected data shall provide statistically valid information about the risk to patients who never have experienced adequate ICD therapy before the ICD replacement investigated in this study. In the future, these statistical risk data can give additional information to implanting physicians, such as whether an ICD replacement can eventually be omitted in those patients who are at very low risk for the occurrence of ICD therapies. All actually available GUIDANT ICDs with CE certificate can be implanted in this trial.
The usual care group will receive generic pelvic floor muscle exercise (PMFX) instructions and demonstrations by the research coordinator at the initial post-operative time point. This will include instruction on how to engage the pelvic floor and specific PFMX prescription. Repetition volume will start at 20 repetitions per day during weeks 1-2; 60/day during weeks 3-4; and 90/day during weeks 5-6, and 100+/day for weeks 7-26. The total number of repetitions will be divided equally between rhythmic (contract and relaxed over one second) and sustained contractions (contract and hold for up to 10 seconds).
Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA (atmospheres), with five-minute air brakes every 20 minutes.
OBJECTIVE: To examine the relationship between C-reactive protein (CRP) and knee pain, and further explore whether this association is mediated by obesity.
METHODS: The population was derived from 1999 to 2004 National Health and Nutrition Examination Survey. Logistic regression was used to analyze the relationship between CRP and knee pain in three different models, and the linear trend was analyzed. A restricted cubic spline model to assess the nonlinear dose-response relationship between CRP and knee pain. Mediation analyses were used to assess the potential mediating role of obesity. Subgroup analyses and sensitivity analyses were performed to ensure robustness.
RESULTS: Compared with adults with lower CRP (first quartile), those with higher CRP had higher risks of knee pain (odds ratio 1.39, 95% confidence interval 1.12-1.72 in third quartile; 1.56, 1.25-1.95 in fourth quartile) after adjusting for covariates (except body mass index [BMI]), and the proportion mediated by BMI was 76.10% (p < .001). BMI and CRP were linear dose-response correlated with knee pain. The odds ratio for those with obesity compared with normal to knee pain was 2.27 (1.42-3.65) in the first quartile of CRP, 1.99 (1.38-2.86) in the second, 2.15 (1.38-3.33) in the third, and 2.92 (1.72-4.97) in the fourth.
CONCLUSION: Obesity mediated the systemic inflammation results in knee pain in US adults. Moreover, higher BMI was associated with higher knee pain risk in different degree CRP subgroups, supporting an important role of weight loss in reducing knee pain caused by systemic inflammation.
Insulin-dependent post-transplant diabetes mellitus (PTDM) was reported in 20% of Prograf-treated kidney transplant patients without pretransplant history of diabetes mellitus in the Phase III study (See Tables Below). The median time to onset of PTDM was 68 days. Insulin dependence was reversible in 15% of these PTDM patients at one year and in 50% at 2 years post transplant. Black and Hispanic kidney transplant patients were at an increased risk of development of PTDM.

Insulin-dependent post-transplant diabetes mellitus was reported in 18% and 11% of Prograf-treated liver transplant patients and was reversible in 45% and 31% of these patients at 1 year post transplant, in the U.S. and European randomized studies, respectively (See Table below). Hyperglycemia was associated with the use of Prograf in 47% and 33% of liver transplant recipients in the U.S. and European randomized studies, respectively, and may require treatment (see ADVERSE REACTIONS).

Insulin-dependent post-transplant diabetes mellitus was reported in 13% and 22% of Prograf-treated heart transplant patients receiving mycophenolate mofetil or azathioprine and was reversible in 30% and 17% of these patients at one year post transplant, in the US and European randomized studies, respectively (See Table below). Hyperglycemia defined as two fasting plasma glucose levels ≥126 mg/dL was reported with the use of Prograf plus mycophenolate mofetil or azathioprine in 32% and 35% of heart transplant recipients in the US and European randomized studies, respectively, and may require treatment (see ADVERSE REACTIONS).
Patients will be treated with localized PBM with a diode laser with continuous wave (laser λ =660 nm; power 100mW;radiant energy: 177J/cm2; 5-s exposure time per point and 0.5J of energy per point) applied directly to the surrounding oral mucosa and to the center of OLP, always by the same operator, twice a week for 4 weeks, totaling 8 session. The number of points will be variable according to the lesion size. The output power of the laser equipment will be evaluated using a power meter (Laser Check; MMOptics LTDA, São Paulo, Brazil) before treatment to confirm the effective mean power as well as the doses applied during the procedure.
PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model.
METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle.
RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group.
CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.
Telmisartan

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

Amlodipine

Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
A computer apparatus and method for identifying and visualizing tumors in a histological image and measuring a tumor margin are provided. A CNN is used to classify pixels in the image according to whether they are determined to relate to non-tumorous tissue, or one or more classes for tumorous tissue. Segmentation is carried out based on the CNN results to generate a mask that marks areas occupied by individual tumors. Summary statistics for each tumor are computed and supplied to a filter which edits the segmentation mask by filtering out tumors deemed to be insignificant. Optionally, the tumors that pass the filter may be ranked according to the summary statistics, for example in order of clinical relevance or by a sensible order of review for a pathologist. A visualization application can then display the histological image having regard to the segmentation mask, summary statistics and/or ranking. Tumor masses extracted by resection are painted with an ink to highlight its surface region. The CNN is trained to distinguish ink and no-ink tissue as well as tumor and no-tumor tissue. The CNN is applied to the histological image to generate an output image whose pixels are assigned to the tissue classes. Tumor margin status of the tissue section is determined by the presence or absence of tumor-and-ink classified pixels. Tumor margin involvement and tumor margin distance are determined by computing additional parameters based on classification-specified inter-pixel distance parameters.
Subjects will be randomized in a 1:1 allocation to either GEMOX or CP after signed consents and baseline evaluations are completed, allowing for safe entry into the study. In order to avoid an unbalanced distribution by baseline characteristics, randomization will be stratified by one factor: disease stage (in a 1:4 proportion for Stage IIIb vs. Stage IV or relapsed disease).
NECON 7/7/7® Tablets are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Oral contraceptives are highly effective. Table I lists the typical accidental pregnancy rates for users of combined oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the NORPLANT® System depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

NECON 7/7/7® has not been studied for and is not indicated for use in emergency contraception.
CKD SMS (Chronic Kidney Disease Self-Management Support) intervention (6,27), guided by the Social Cognitive Theory, through the manipulation of self-efficacy, is educational for the adult with CKD in early stages where a primer will be used which contains a primer that explains the functions of the kidneys, the first signs and symptoms of CKD and the strategies to control or delay the progression of CKD, such as the benefits of maintaining a healthy lifestyle and adherence to treatment. Also, a diary for participants to record side effects of medications, monitor their clinical data, treatment plan and questions for medical appointments.