anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Histopathological heterogeneity is a hallmark of prostate cancer (PCa). Using spatial and parallel single-nucleus transcriptomics, we report an androgen receptor (AR)-positive but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small cell carcinoma. Such small cell-like PCa (SCLPC) is clinically aggressive with low AR, but high stemness and proliferation, activity. Molecular characterization prioritizes protein translation, represented by up-regulation of many ribosomal protein genes, and SP1, a transcriptional factor that drives SCLPC phenotype and overexpresses in castration-resistant PCa (CRPC), as two potential therapeutic targets in AR-indifferent CRPC. An SP1-specific inhibitor, plicamycin, effectively suppresses CRPC growth in vivo. Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.
The standard of care chemotherapy for first-line advanced pancreatic adenocarcinoma is FOLFIRINOX, NALIRIFOX, or gemcitabine/nab-paclitaxel. However, multiple studies suggest that basal-like subtypes of pancreatic adenocarcinoma do not respond to FOLFIRINOX. Based upon existing retrospective analyses, the addition of epidermal growth factor receptor (EGFR) inhibitors such as erlotinib to gemcitabine and nab-paclitaxel suggest improved rates of response in subjects with basal-like pancreatic adenocarcinoma compared to FOLFIRINOX.

Subjects with a classical subtype will be treated on standard-of-care oxaliplatin-based triplet chemotherapy. Subjects with basal type will receive the erlotinib combination treatment. The purpose of this study is to find out the best dose of the erlotinib combination treatment. The erlotinib combination treatment is not FDA-approved. However, the combinations of erlotinib, gemcitabine, and nab-paclitaxel are both approved by the FDA for the treatment of pancreatic cancer. The standard of care treatments are both FDA-approved. All three drugs have been used in combination before in other clinical trials and a certain amount of safety data exists.

In the basal-like arm of this study, a two-stage utility of bayesian optimal interval ( U-BOIN) design will be used to evaluate the range of safe and admissible doses in Stage 1 and the optimal best dose (OBD) in Stage 2 basal subjects. After the determination of the OBD, an expansion cohort will be enrolled to obtain additional precision of the overall response rate (ORR). In total, 52 patients will be enrolled in the basal-like arm. Separately, 52 patients with "classical" tumors will be enrolled in a parallel arm and given standard-of-care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX) to determine long-term outcomes including overall survival, objective response rate, and progression-free survival. This is to test the safety and effectiveness (how well a treatment works) of both treatments, depending on the cancer type.
CSP: In this group polyps will be removed with the cold snare polypectomy technique, as a single piece. Additionally, a 1-2mm of normal tissue around the small polyp will also be ensnared in the CSP.
The present invention relates to a combination of at least two amphenicol antibiotics (including any salt or dosage form thereof) with significance of synergistic activity. The application of patterns include the dosages, the major ingredients (include different types of amphenicol salts and dosage forms), and the combinations of amphenicol. The present combinations include at least two individual amphenicol antibiotic that at any concentrations above 1/128 of their original minimum inhibition concentrations (MICs). These newly invented combinations can be used for therapeutic or prophylactic purposes on veterinary and human medicine. These combinations not only perfectly inhibit amphenicol-sensitive bacteria, but also perfectly inhibit amphenicol-resistant bacteria. The active integrations of the present combinations can effectively decrease the dosages of individual amphenicol antibiotic, and thereby reduce the antibiotic residues in products of food-producing animal origin, decrease the possible toxicities of the production environments and non-target animals.
INTRODUCTION: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.
METHODS: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes.
RESULTS: Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality.
CONCLUSIONS: Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.
Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.
Meal consumption, especially if high in fats, sugars and total energy content, leads to a transient rise in blood glucose and lipids. The extent of glycemic and lipidemic postprandial responses have been linked to the progression of cardiovascular and other chronic degenerative diseases, such as type 2 diabetes and Alzheimer through a substantial increase in oxidative stress, systemic inflammation, and endothelial dysfunction. In addition, some studies have shown that consuming a high fat meal is associated with a postprandial increase in plasma and serum endotoxin concentrations in humans. LPS, lipopolysaccharide, is considered a major predisposing factor for inflammation-associated diseases such as atherosclerosis, sepsis and obesity. Therefore, following a correct dietary model may be beneficial in order to limit postprandial excursion and to modulate hormonal responses involved in satiety.

The physiological postprandial response depends on several factors, both intrinsic, such as natural characteristic of food, and extrinsic, such as the way in which food is processed. Thus, the present study aims at evaluating if the reformulation of some commercial confectionery products can lead to an improvement of the nutritional profile, through a decrease of postprandial metabolic and hormonal, oxidative stress, inflammation and endotoxaemia responses in comparison with commercial confectionery products (snacks).
Serious and rarely fatal anaphylactic reactions have been reported in patients receiving therapy with tramadol. When these events do occur it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis, and Stevens-Johnson syndrome. Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Tramadol HCl 37.5 mg/Acetaminophen 325 mg (see CONTRAINDICATIONS).

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Tramadol HCl 37.5 mg/Acetaminophen 325 mg tablets immediately and seek medical care if they experience these symptoms. Do not prescribe Tramadol HCl 37.5 mg/Acetaminophen 325 mg tablets for patients with acetaminophen allergy.
The initial dosage varies from 0.75 mg to 9 mg a day depending on the disease being treated.

It Should Be Emphasized That Dosage Requirements Are Variable And Must Be Individualized On The Basis Of The Disease Under Treatment And The Response Of The Patient.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage that maintains an adequate clinical response is reached.

Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

In the treatment of acute exacerbations of multiple sclerosis, daily doses of 30 mg of dexamethasone for a week followed by 4 mg to 12 mg every other day for one month have been shown to be effective (see Error! Hyperlink reference not valid.: Error! Hyperlink reference not valid.).

In pediatric patients, the initial dose of dexamethasone may vary depending on the specific disease entity being treated. The range of initial doses is 0.02 mg to 0.3 mg/kg/day in three or four divided doses (0.6 mg to 9 mg/m2bsa/day).

These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders, the following dosage schedule combining parenteral and oral therapy is suggested:
) 1. Technical Result Increase in efficiency of medicaments use, widening of spectrum of action, reduce of toxicity. 2. Essence A method comprises preparing a reaction product by reacting at least one alkaloid with a phosphorus derivative which contains at least one aziridine group in organic solution at elevated temperature and washing the reaction product. 3. Field of Application Pharmacology.
Laparoscopic cholecystectomy (LC) is an increasingly common operation in the pediatric population, although numbers remain significantly lower than in adults. Currently, this operation is performed by both adult and pediatric surgeons and there is no consensus as to whether specialist low-volume or adult high-volume surgeons should be performing this operation. A literature search was performed to compare the outcomes following pediatric LC when performed by adult or pediatric surgeons. 19,993 patients were included in this analysis. Overall, post-operative complications were reduced when LC was performed by high-volume adult surgeons, along with reduced length of stay and associated cost. Overall morbidity following LC in children is comparable to adults. When performed by higher volume adult surgeons, there was a statically significant reduction in post-operative complications and re-admission rates. Morbidity was also reduced in patients with simple cholelithiasis. Initial results show that in pediatric patients presenting with cholelithiasis, LC performed by a high-volume adult general surgeon is safer. In more complex children with needs from other specialist pediatricians, surgery performed by a pediatric surgeon is recommended. Further research with direct comparisons is still required.
The aim of this study was to investigate the effects of miR-424-5p on biological behaviors and angiogenesis of the HTR-8/SVneo Cells. Our study included 60 parturient women, which were divided into an PA group (placenta accreta, n = 30) and a normal group (normal placenta, n = 30). QPCR was used to measure the expression of miR-424-5p in placental tissues. The effects of the miR-424-5p mimic on proliferation, migration, and invasion of human HTR-8/SVneo cells and angiogenesis were analyzed. The potential modulated relationship between miR-424-5p and low-density lipoprotein receptor-related protein-6 (LRP6) was demonstrated by luciferase assay. The expression of LRP6, β-catenin, matrix metalloproteinase-2 (MMP-2), placental growth factor (PGF) and vascular endothelial growth factor (VEGF) were measured by qPCR and Western blot assays. The expression of miR-424-5p in the PA group was significantly decreased than that in the normal group. The expression of miR-424-5p has negative correlation with blood loss. Upregulation of miR-424-5p significantly suppressed the cell proliferation, migration, and invasion of HTR-8/SVneo cells in vitro, as well as the tube formation of human umbilical vein endothelial cells (HUVECs). The luciferase assay demonstrated that LRP6 was a target of miR-424-5p. The expression of LRP6, β-catenin, MMP-2, PGF and VEGF were also decreased with upregulation of miR-424-5p (p < 0.05). The inhibitory effects of miR-424-5p on HTR-8/SVneo cells and angiogenesis were enhanced by downregulation of LRP6, but were reversed by upregulation of LRP6. The present study suggests that downregulation of miR-424-5p is related to the occurrence of PA. Enhancing miR-424-5p inhibits proliferation, migration, invasion and angiogenesis of the HTR-8/SVneo cells through targeting LRP6 mediated β-catenin, providing more insights about PA.
Patients will take placebo for 3 months. Placebo is manufactured by the same company as the L-carnitine and will have a similar appearance.
The objective of this prospective randomized two-group repeated measures experimental design is to determine the efficacy of the HEART (Heart Failure Exercise and Resistance Training) Camp behavioral exercise training intervention on long-term adherence to exercise at 18 months in patients with HF. A sample size of 246 subjects with heart failure will be recruited over a 3 year period. All subjects will receive a cardiopulmonary exercise test and 9 supervised exercise training sessions during a 3 week run-in period prior to randomization. Subjects completing 6 of 9 training sessions will be randomized to the HEART Camp Intervention group (HC) or to an enhanced usual care (EUC) exercise group. The HC intervention group will receive cognitive-behavioral strategies that address the intervention components of knowledge, attitudes, self-efficacy, behavioral self-management skills and social support. The EUC group is provided access to the exercise facility and regular facility staff for the 18 month study period. Our central hypothesis is that the HC group will have significantly better adherence to exercise at 18 months. We will test our hypothesis with the following Specific Aims: Aim 1. To evaluate the effect of HEART Camp on adherence to exercise (measured by self-report and validated by heart rate monitor); Aim 2. To evaluate which components of the HEART Camp intervention mediate the effects of the intervention on adherence; Aim 3. To evaluate the effect of HEART Camp on specific health outcomes; Aim 4. To explore selected demographic variables (age, race, gender, body mass index and left ventricular ejection fraction) as potential moderators of the effect of the HEART Camp intervention on adherence; and Aim 5. To explore the perceptions and experiences that contextualize exercise adherence.
The present invention relates to novel quinoline derivatives of formula (I) wherein, R1? is a straight chain or cyclic lower alkyl group having 1 to 3 carbon atoms, a straight chain or cyclic lower alkyl group having 1 to 3 carbon atoms which is substituted with a halogen atom, a phenyl group or a phenyl group substituted with one or two halogen atoms; R2? is a hydrogen atom, a lower alkyl or amino group; R3? is a halogen atom or a substituted or unsubstituted heterocyclic group represented by formula (A) which contains at least one nitrogen atom as a hetero atom in the ring, wherein R6?, R7?, R8? and R9? are each hydrogen atoms or lower alkyl groups, or two of these groups may form a bond, m and n are 0 or 1, and Ca?-Cb? may not form a bond, or is single or double bond; X is nitrogen atom or C-R4? wherein R4? is hydrogen or halogen atom, or lower alkyl or lower alkoxy group; and Y and Z are each hydrogen atoms, or electron withdrawing groups, for example, ester, cyano, nitro, acyl or substituted acyl, substituted or unsubstituted amide, lower alkylsulfoxy or lower alkylsulfonyl group, and pharmaceutically acceptable acid addition salts thereof, and also to processes for preparing these compounds. The present invention also provides an antibacterial composition comprising a compound of formula (I) or its acid addition salt as an active ingredient and pharmaceutically acceptable excipients. The novel quinoline derivatives of the present invention have an excellent antibacterial activity against bacteria or bacteroides.
Demographic data of all participants were recorded. Tampa Scale of Kinesiophobia (TSK), Beck Depression Inventory (BDI), Quality of Life Scale Short Form-36 (SF-36), International Physical Activity Questionnaire Short Form (IPAQ-SF), Functional Ambulation Classification (FAS), Functional Independence Measure (FIM), Expanded Disability Status Scale (EDSS) were implemented.
BACKGROUND: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer.
METHODS: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay.
RESULTS: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients.
CONCLUSION: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.
Core-shell particles have a hydrophobic core and a shell formed of o containing hyperbranched polymers (HP). The HP can be covalently bound to the one or more materials that form the core or coated thereon. The HP coating can be modified to adjust the properties of the particles. For example, unmodified HP coatings resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HP coating can be chemically modified to form functional groups that react with functional groups on tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HP coated nanoparticles. In some embodiments, the particles include cosmetic, therapeutic, diagnostic, nutraceutical, and/or prophylactic agents, such as those used as sunblock compositions.
Community health workers (CHWs) will conduct screening for CVD risk using a mobile phone application to assess risk and to schedule appointments at primary care centers (PCCs). The screening process will be non-invasive and no surgical, pharmaceutical, or other testing procedures will be utilized for screening of CVD risk by CHWs. If the CHW calculates the risk of CVD to be \> 10%, s/he will schedule a clinical visit with a health professional at one of the PCCs for further assessment and/or appropriate treatment. An automatic reminder messaging system will send reminder messages about upcoming appointments to the participants.
After analgesia endoscopy will be performed. After diagnostic endoscopy if there is not any gastric pathology that would be contraindication for Botox injection and balloon placement, 200 U of botulinum toxin A will be injected to the antrum and the fundus. After 24 hour or 1 week the second procedure (placement of gastric balloon) will be performed. And Starting from first hour until 1 week, patient's nausea-vomiting and retching scores, re-admission to hospital, quality of life scores will be documented.