anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The Warburg effect occurs both in cancer cells and in inflammatory macrophages. The aim of our work was to demonstrate the role of PI3K-Akt-mTOR axis in the Warburg effect in HL-60 derived, rat peritoneal and human blood macrophages and to investigate the potential of selected inhibitors of this pathway to antagonize it. M1 polarization in HL-60-derived and human blood monocyte-derived macrophages was supported by the increased expression of NOS2 and inflammatory cytokines. All M1 polarized and inflammatory macrophages investigated expressed higher levels of HIF-1α and NOS2, which were reduced by selected kinase inhibitors, supporting the role of PI3K-Akt-mTOR axis. Using Seahorse XF plates, we found that in HL-60-derived and human blood-derived macrophages, glucose loading reduced oxygen consumption (OCR) and increased glycolysis (ECAR) in M1 polarization, which was antagonized by selected kinase inhibitors and by dichloroacetate. In rat peritoneal macrophages, the changes in oxidative and glycolytic metabolism were less marked and the NOS2 inhibitor decreased OCR and increased ECAR. Non-mitochondrial oxygen consumption and ROS production were likely due to NADPH oxidase, expressed in each macrophage type, independently of PI3K-Akt-mTOR axis. Our results suggest that inflammation changed the metabolism in each macrophage model, but a clear relationship between polarization and Warburg effect was confirmed only after glucose loading in HL-60 and human blood derived macrophages. The effect of kinase inhibitors on Warburg effect was variable in different cell types, whereas dichloroacetate caused a shift toward oxidative metabolism. Our findings suggest that these originally anti-cancer inhibitors may also be candidates for anti-inflammatory therapy.
OBJECTIVE: The aim of this study was to investigate the prevalence of comorbidities and cardiovascular (CV) risk factors (RFs) in treatment-naive patients with early psoriatic arthritis (ePsA) and to identify factors that contribute to metabolic burden in ePsA.
METHODS: This was an observational longitudinal multicenter cohort study. Clinical and demographic characteristics, CV RFs, and comorbidities were compared in patients newly diagnosed with psoriatic arthritis (PsA) and sex- and age-matched controls. In patients with PsA, comorbidities were reevaluated after one year's follow-up because the disease activity changed.
RESULTS: Sixty-seven patients with ePsA and 61 healthy volunteers were included. The rate of comorbidities was similar in patients with ePsA and in healthy controls; 82.1% of patients with ePsA had CV RFs at baseline as compared with 62.3% of healthy volunteers (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.14-2.0). Patients with ePsA had higher odds of having multiple (two or more) comorbidities (OR 1.9, 95% CI 1.2-3.0) and multiple CV RFs (OR 2.1, 95% CI 1.3-3.2) than the controls. Comorbidities or CV RFs in patients with ePsA were not influenced by duration of skin psoriasis. Dyslipidemia was the most prevalent comorbidity in the PsA cohort (64.2% vs 39.3% in controls; OR 1.7, 95% CI 1.2-2.5). Patients with ePsA had, on average, above normal body mass index (mean ± SD 28.82 ± 4.5) and a higher rate of obesity (40.3% vs 18.3% in controls; OR 1.9, 95% CI 1.1-3.2). After 1 year, although disease activity scores improved, the proportion of patients with comorbidities and CV RFs did not increase or drop.
CONCLUSION: Our data imply that patients with PsA already have higher comorbidities and CV burden at early stages of the disease, suggesting that these are not only a consequence of long-lasting disease and chronic systemic inflammation.
INTRODUCTION: Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty.
AIM: We aimed to evaluate the genetic changes in Indian HA-patients that are associated with the development of inhibitors.
METHODS: All HA-patients with inhibitors who availed coagulation-laboratory services from January-2015 till December-2021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity-matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse-shifting-PCR. Inversion-negative patients were further assessed by targeted NGS, MLPA.
RESULTS: Thirty HA-patients with inhibitors were identified. All had severe-HA. Thirty severe-HA-patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion-negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion-negative patients with and without inhibitors. Seven novel-variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor-positive patients, and one frameshift variant in inhibitor-negative patient. After adjusting for clinical risk-factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41-56.3)].
CONCLUSION: Intron 22 inversions are the commonest variant in Indian patients with severe-HA. Large deletions predispose to inhibitor development independent of clinical risk factors.
The invention provides a preparation method of a drug-loaded silicone grease ultrasonic contrast agent. The preparation method comprises fully dissolving silicone grease, polyethylene glycol phosphate derivatives and a fat-soluble anticancer drug in an organic solvent, adding water into the solution, carrying out whirling, removing the organic solvent, supplying water with a volume 3 times that of the solution into the solution, carrying out ultrasonic disintegration by an ultrasonic disintegrator, simultaneously and fast adding liquid fluorocarbon into the solution to obtain a pre-emulsion, and carrying out dialysis on the pre-emulsion in PBS for 1h to obtain a product. The preparation method has simple processes. The product has the average particle size of about 100nm and is conducive to aggregation at a tumor position by internal EPR effects. Siloxane silicone grease network distribution substantially improves structure stability and prolongs internal blood circulation time. Through HIFU, the drug-loaded silicone grease ultrasonic contrast agent release drugs at a local part of tumor tissue, drug treatment targeting is improved, HIFU treatment effects are substantially improved and HIFU-chemotherapy combined treatment is realized.
Ramipril and ramiprilat inhibit ACE in human subjects and animals. Angiotensin converting enzyme is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In hypertensive patients with normal renal function treated with ALTACE alone for up to 56 weeks, approximately 4% of patients during the trial had an abnormally high serum potassium and an increase from baseline greater than 0.75 mEq/L, and none of the patients had an abnormally low potassium and a decrease from baseline greater than 0.75 mEq/L. In the same study, approximately 2% of patients treated with ALTACE and hydrochlorothiazide for up to 56 weeks had abnormally high potassium values and an increase from baseline of 0.75 mEq/L or greater; and approximately 2% had abnormally low values and decreases from baseline of 0.75 mEq/L or greater [see Warnings and Precautions (5.8)]. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

The effect of ramipril on hypertension appears to result at least in part from inhibition of both tissue and circulating ACE activity, thereby reducing angiotensin II formation in tissue and plasma.

Angiotensin converting enzyme is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasopressor peptide, play a role in the therapeutic effects of ALTACE remains to be elucidated.

While the mechanism through which ALTACE lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, ALTACE has an antihypertensive effect even in patients with low-renin hypertension. Although ALTACE was antihypertensive in all races studied, Black hypertensive patients (usually a low-renin hypertensive population) had a blood pressure lowering response to monotherapy, albeit a smaller average response, than non-Black patients.
1336802 Cephalosporin solvates ELI LILLY & CO 19 Jan 1972 [20 Jan 1971] 2657/72 Heading C2A Novel cephalosporin complexes of N,N- dimethylformamide (DMF) or N,N-dimethylacetamide (DMA) with a cephalosporin acid (which is defined as being any compound having the cephem ring structure with a carboxylic acid group attached in the 4-position of the dihydrothiazine ring) are prepared by: (a) mixing DMF or DMA with an ester or salt thereof of the cephalosporin acid in which the ester group is removable by treatment with a reducing agent in an acidic medium; (b) treating the mixture with a reducing agent in acidic medium to remove the ester group; and (c) adding a basic substance to raise the pH sufficiently to precipitate the desired complex. The preferred cephalosporin acids have the formula wherein R<SP>1</SP> is hydrogen or an acyl group of formula in which B is -NH 2  and W is phenyl 3- or 4- hydroxyphenyl, 4 - (α - amino - C 1  to C 3  alkyl)- phenyl, 4 - chlorophenyl, 3 - chloro- or 3,5- dichloro - 4 - hydroxyphenyl, 2- or 3 - thienyl, or sydnonyl; and A is hydrogen, -O-CO- (C 1  to C 4  alkyl), -O-CO- (C 4  to C 7  cycloalkyl), or -X-Z where X is O or S and Z is C 1  to C 4  alkyl, 1,3,4-thiadiazol-2-yl, or 1-methyl- 1H - tetrazol - 5 - yl. When the ester of the cephalosporin acid contains a free amino group, this is preferably blocked, before carrying out step (a) above, with a blocking group which is removable by acidic hydrolysis, subsequent removal of this blocking group being effected by the acidic medium used in step (b). The cephalosporin acid complex from step (c) may be purified by (d) dissolution in acidified DMF or DMA which may contain up to 40% by volume of a miscible polar liquid (e.g. water) and then (e) adding a base to reprecipitate the purified complex. The complex may be converted to the free cephalosporin acid by (f) dissolving in acidified water, heating to 40 to 70 C. and then (g) adding a base to bring the solution to the isoelectric pH of the cephalosporin, when the latter precipitates in the zwitterion form. The process (a)-(g) provides a means for obtaining pure cephalosporin acids from their impure solutions. Pharmaceutical compositions comprise an antibiotic cephalosporin, that has been prepared by the procedure (a) to (g) above, together with a suitable carrier.
Indium lung is an occupational lung disease caused by exposure to indium-tin-oxide (ITO) dust. Compared to other occupational lung diseases, indium lung has a shorter latency period and the respiratory status continues to worsen even after exposure to the work environment improves. Paraseptal emphysema which affects mainly the subpleural area is seen on chest images obtained via computed tomography (CT), regardless of the smoking history. However, the pathogenesis of emphysema in indium lung is still unclear. Therefore, we re-evaluated the pathology of three previously reported cases of indium lung. Paraseptal emphysema was observed in both smokers and nonsmokers. Obstructive respiratory impairment worsened over time in the cases with paraseptal emphysema. Many alveolar walls were destroyed independent of the presence or absence of emphysetamous changes or fibrosis. Moreover, bronchiolitis was found to be less common in indium lung than in asbestosis (the most common occupational lung disease) or common cases of chronic obstructive pulmonary disease caused by smoking. It has been shown that ITO causes protease anti-protease imbalance, oxidant-antioxidant imbalance, and continuous, abnormal inflammation (the three major causes of emphysema). In addition, nano-sized ITO is less likely to be trapped in the upper airways and may easily reach the subpleural alveoli. Furthermore, ITO may continue to cause sustained tissue injury at the alveolar level potentially resulting in emphysema. Further studies are needed to elucidate the detailed pathogenesis of indium lung by comparing it with other occupational lung diseases.
The objective of this study is to compare the effectiveness of insulin alone vs the combination of insulin and metformin in treating patients with gestational diabetes (GDM). Currently, outside of pregnancy, the treatment of type 2 diabetes mellitus (T2DM) with both metformin and insulin is superior to using insulin alone. In pregnancy, insulin alone has traditionally been used, though some advocate the use of metformin alone as primary therapy. There have been no trials published to date specifically comparing combination therapy to insulin alone. Our hypothesis is that the combination of metformin and insulin will improve overall control of blood glucose, the improvement of which has been demonstrated to improve maternal and neonatal outcomes. Control of blood glucose will be determined by hemoglobin A1c at the time of delivery.
###  Teratogenic Effects: Pregnancy Category B.

Oral reproduction studies were performed at doses of 10 mg/kg/day in mice, 1,000 mg/kg in rats and 125 mg/kg/day in rabbits. These doses correspond in each species, respectively, to approximately 200, 40000, and 10000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis. Inhalation reproduction studies were conducted in rats and rabbits at doses of 1.5 and 1.8 mg/kg (approximately 60 and 140 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). These studies demonstrated no evidence of teratogenic effects as a result of ipratropium bromide. At oral doses 90 mg/kg and above in rats (approximately 3600 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis) embryotoxicity was observed as increased resorption. This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Atrovent® HFA (ipratropium bromide HFA) Inhalation Aerosol should be used during pregnancy only if clearly needed.
Patients from 18 to 60 years of age recovering after traumatic brain injury are recruited to participate in a multidisciplinary telerehabilitation containing total of 20 video meetings over a period of 4-5 months. The study design consists of a 3-day visit in rehabilitation ward for the pre-treatment clinical assessments and education on the telerehabilitation protocol. A self-exercise program is supervised and monitored using a health platform application on a tablet computer through weekly video meetings. A digital diary recordings enable the therapists to track on the progress of therapies. The primary goal is to achieve the individual goals set in the Goal Attainment Scaling. The secondary goals are related to the improvement of psychological well-being (BDI) and quality of life (WHOQOL-Bref).
Oculeve device, intranasal (test) application for approximately 3 minutes followed by oculeve device, extranasal (control) application for approximately 3 minutes followed by sham device, intranasal (control) application, for approximately 3 minutes on Day 0. There was rest period of 60 minutes before proceeding to the next application.
The present invention is related with polypeptides which show an increased activity compared with tilapia growth hormone. These polypeptides are able to stimulate growth, survival and the quality of fish and crustaceans larvae. Also, they increase the defences against pathogens and stimulate parameters related with the immune system of aquatic organisms. The polypeptides encoding genes were cloned into a  Pichia pastoris  expression vector. This vector allows the extracellular expression of the target proteins. The culture supernatants which contain the target polypeptides were administrated by immersion baths or as a feed additive to aquatic organisms.
Dry needling was performed using sterile plastic cylindrical guide needles (25 mm length, 0.25 mm diameter) The needles were inserted 5 mm deep into hypertonic and irritable nodules (trigger points, TrPs) within the masseter and temporalis muscles. Each needle was rotated twice clockwise and then removed after remaining in the TrPs for a total of 20 minutes. The treatment was administered in three sessions, each one week apart.
Glomerulonephritis is one of the major disease manifestations of systemic lupus erythematosus (SLE). The treatment of membranous (type V) lupus nephritis, a subset that carries a high morbidity, remains unsatisfactory. Recent studies suggest that immunosuppressive therapy targeted against the calcineurin pathway of T-helper cells, for example, tacrolimus, may be effective in the treatment of primary membranous nephropathy. The investigators plan to conduct an open-label single-arm study of the efficacy and safety of tacrolimus in the treatment of membranous nephropathy secondary to SLE. Twenty patients with biopsy-proven membranous nephropathy secondary to SLE will be recruited. They will be treated with oral prednisolone and tacrolimus for 6 months, followed by 6 months of maintenance steroids alone. Proteinuria, renal function, clinical and serologic lupus activity will be monitored. Complete remission is defined as 24-hour urinary protein excretion to less than 0.5 gm/day. This study will explore the potential role of tacrolimus in the treatment of membranous lupus nephritis, which is usually resistant to conventional therapy.
The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (\>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment.
BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a routine preoperative method for evaluating suspicious axillary lymph nodes (ALNs) in patients with breast cancer. However, a range of reasons such as morphological pitfalls, technical artifacts, and sampling errors restrict the sensitivity and accuracy of FNAC. This retrospective study investigated the diagnostic value of GATA-binding protein 3 (GATA-3) immunocytochemistry for FNAC.
METHODS: Breast cancer patients who underwent preoperative FNAC for suspicious ALNs, relevant GATA-3 immunocytochemistry, and postoperative status of ALNs were reviewed from the period of March 2020 to February 2022. Altogether, 102 patients were included in the study. FNAC material smears stained with hematoxylin and eosin was initially assessed by two cytopathologists and categorized into five groups: nondiagnostic, negative, atypical, suspicious, and positive for malignancy. Only group of cells positive for malignancy was considered positive. For each case, two selected slides were digitized (whole slide imaged) at ×40 magnification and decolored for GATA-3 immunocytochemistry. The expression of GATA-3 was scored ranging from 0 to 9 (Score ≥3: Positive, Score ≤2: Negative). If either FNAC or GATA-3 immunocytochemistry was positive or the combined test positive, then the case was considered positive. The sensitivity, specificity, and accuracy of FNAC, GATA-3 immunocytochemistry, and combined FNAC/GATA-3 immunocytochemistry were analyzed by χ2 and Fisher's tests.
RESULTS: The mean age of the study participants was 50.62 (ranging: 30-73 years). Invasive breast carcinoma (not otherwise specified) accounted for most histological subtypes, and grade 2 was the leading Nottingham grade. Sixteen cases directly underwent mastectomy while the other 86 patients had neoadjuvant therapy. A more serious diagnosis was made based on GATA-3 detection in 22.5% (n = 23) of 102 cases. Of the 23 cases, metastasis was confirmed by GATA-3 detection in 21 cases, and an uncertain diagnosis was ascertained based on GATA-3 immunocytochemistry in 2 with nondiagnostic FNAC results. The sensitivity (77/87, 88.5%) of GATA-3 detection for distinguishing malignancies from benign lesions was higher than that of FNAC alone (62/87, 71.3%) (p < .05).
CONCLUSIONS: GATA-3 immunocytochemistry exhibited high diagnostic efficacy in distinguishing malignant breast cancer cells. Moreover, combined FNAC and GATA-3 immunocytochemistry achieved optimal results in terms of reducing the false-negative rate and promoting accuracy.
This pilot study of N9 as induction chemotherapy will enroll 30 patients with newly-diagnosed HR-NB. A first cohort of \>1 to 12-year old, and a second cohort of extended age \<19 years old. Both cohorts will be analyzed together.
The present invention refers to a novel pharmaceutical composition of Losartan and Atorvastatin for treating hypertension associated with dyslipidemia. On the other hand hypertension is defined as the chronic increase in the systolic and diastolic blood pressure, also representing one of the most frequent chronic diseases suffered by humanity. The blood pressure is a value that acquires relevance when the blood pressure values, diastolic (over 80 mmHg) and systolic (increases higher than 120 mmHg, cause a high morbid-mortality in most of the individuals of all studied populations, at any age and both sexes and, according to the World Health Organization and the international society of hypertension, the levels of blood pressure may result optimum when the systolic blood pressure is lower than 120 mmHg and the diastolic pressure 80 mmHg. Said values are based on the determination of the blood pressure in clinics and not in ambulatory conditions. For ambulatory conditions the pressure is controlled for 24 hrs. and has values higher than 125/80 mmHg.
<P>PROBLEM TO BE SOLVED: To provide a method, etc., for ameliorating disease symptoms caused by e.g. mood disorder or related disorder such as depression or anxiety disorder and a method for searching active ingredients for medicines effective for treating the mood disorder or the related disorder and to provide a model mammal, etc., utilized in the method.  <P>SOLUTION: The method for ameliorating disease symptoms caused by mood disorder or related disorder comprises a step for excessively making either one of the following proteins exist in the brain in mammal. These proteins includes (a) an activated Gm1 protein having a specific sequence and (b) a protein composed of an amino acid sequence in which one or a plurality of amino acids are lost, added or substituted, having functions as the activated Gm1 protein in the activated Gm1 protein having the specific sequence. The mammal or the like is utilized by applying the method.  <P>COPYRIGHT: (C)2007,JPO&INPIT