anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs).
METHODS: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs.
RESULTS: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway.
CONCLUSIONS: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.
The safety and effectiveness of Methylphenidate Transdermal System in pediatric patients less than 6 years have not been established. Long-term effects of methylphenidate in children have not been well established.

The safety and effectiveness of Methylphenidate Transdermal System for the treatment of ADHD have been established in pediatric patients 6 to 17 years.

Long Term Suppression of Growth

Growth should be monitored during treatment with stimulants, including Methylphenidate Transdermal System. Children who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions (5.8)].

Juvenile Animal Toxicity Data

Rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only.

Studies with transdermal methylphenidate have not been performed in juvenile animals. In a study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (Postnatal Day 7) and continuing through sexual maturity (Postnatal Week 10). When these animals were tested as adults (Postnatal Weeks 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose. The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day. The clinical significance of the long-term behavioral effects observed in rats is unknown.
Breast cancer is the most common malignancy among women in the U.S. and the primary prevention of this disease is a major public health issue. The U.S. Preventive Services Task Force and other professional organizations recommend that clinicians discuss chemoprevention with high-risk women. Breast cancer chemoprevention with anti-estrogens, such as tamoxifen, raloxifene, exemestane, and anastrozole, is under-utilized, despite several randomized controlled trials demonstrating a 40-65% decrease in breast cancer incidence among high-risk women. Compounding this underutilization is the fact that a large proportion of women may be unaware of their high-risk status due to the investigators' inability to adequately screen them in the primary care setting. Further research is needed to determine how knowledge about breast cancer, actual/perceived risk, and risks/benefits of chemoprevention are best communicated to women in order to promote breast cancer prevention strategies.

The investigators hypothesize that combining a patient-centered decision aid with a physician-centered decision support tool integrated into clinic workflow will improve accuracy of breast cancer risk perception, facilitate referrals for specialized risk counseling, and increase chemoprevention uptake. We anticipate that the BNAV tool will facilitate referrals to the breast clinic by primary care providers (PCPs) and that the RealRisks decision aid will prime high-risk women to seek these referrals. The primary endpoint is uptake of a selective estrogen receptor modulator (SERM) or Aromatase inhibitor (AI) for breast cancer chemoprevention at 6 months (after the next primary care appointment) in the active arm compared to usual care.
Aim 1: To assess the feasibility, acceptability, and content utility of the ECHO program among the clinicians in the participating primary care clinics. Data will be collected to assess successful program implementation and participant engagement. We will document outreach efforts, reporting why clinics decline to participate and as well as the initial motivations of those who agree. Data will be collected from participating clinicians: a pre-training questionnaire about their prior experience with ACP and dementia; feedback at the end of each session; and a longer questionnaire at the end of the training that measures intentions to engage in ACP, their understanding of dementia, their confidence in engaging patients and families in ACP, and what barriers they expect to encounter. Attendance will be documented, and ECHO sessions will be recorded so participation and trainee engagement can be assessed. At the end of the follow-up period, clinicians will participate in interviews focused on barriers to and facilitators of ACP in the context of dementia. Feasibility and acceptability of this intervention will be evaluated using descriptive and qualitative analyses of these data.

Aim 2: To pilot test the ascertainment of outcomes for the ADVANCE-PC program in the 3-month period when trained clinicians are attempting to conduct ACP routinely in their clinics. The primary outcome will be the proportion of patients with dementia and/or their care partners seen by participating clinicians who are engaged in ACP. To pilot test pragmatic assessment of this outcome, we will work with clinics to determine how the number of patients with dementia seen in a defined period (the denominator) and number who are engaged in ACP (the numerator) can be efficiently identified in by each clinic using their electronic health record (EHR). We will collect information on EHR functionality and current dementia and ACP documentation during Months 1-3 and integrate support for documentation and measurement into the training. Our secondary outcomes are clinician confidence, intentions, and behavior related to ACP. These will be evaluated during the ECHO program using questionnaires modeled after data collection activities routinely used by clinics for quality improvement and formally measured and analyzed using research questionnaires pre and post completion of the ECHO program and a semi structured interview at the end of the follow-up period.
Before initiating the study, all potential subjects were invited to attend an educational program that explained the purpose and methodology of this study. After getting informed consent from patients, demographic data including age, sex, medical history (including comorbidities and risk factors), current medicine, lifestyle habits, height (cm), and weight (kg) were recorded, and body mass index (BMI) was calculated as weight divided by height squared (kilograms per square meter, kg/m2). The included subjects need to perform transthoracic echocardiography or provide an echocardiographic examination within one month. CAD diagnosis was determined based on the results of the coronary angiography, using stenosis 50% cutoffs considered have coronary diseases or not.

Consecutive patients of both sexes with coronary angiography from outpatient or inpatient departments of Fuwai Hospital were recruited into the study. The inclusion criteria were Chinese, aged 35 to 75 years with CAD verified by coronary angiography, and able to give informed written consent. The subjects were excluded if they had New York Heart Association Class III-IV degree with ejection fraction \< 45%, severe pulmonary disease, significant psychiatric disease, or history of pharyngeal surgery for OSA or current use of CPAP treatment for OSA. They were also excluded if they declined to participate or were unable to provide informed consent.
Participants in this group will be administered a dose of alcohol by researchers in our mobile lab. The dose is designed (based on participant sex and body weight) to bring blood alcohol concentration to .06 g/dL.
Reactive arthritis, previously known as Reiter's Syndrome or Disease was a post-dysenteric, asymmetrical acute large joint polyarthritis, with fever, conjunctivitis, iritis, purulent urethral discharge, rash and penile soft tissue swelling. Although the eponym was given to Hans Reiter, various forms of the condition have been recorded in history a few hundred years before Reiter. Two French doctors, Noel Fiessinger (1881-1946) and Edgar Leroy (d. 1965), presented a paper at la Societe des Hopitaux-in Paris on the 8th December 1916 on dysentery in 80 soldiers on the Somme, and four of whom developed a "syndrome conjunctivo-uretro-synovial". Their paper was given 4 days before Reiter's presentation on 12th December 1916 at the Society of Medicine in Berlin, on a German army officer with an illness similar to those described by Fiessinger and Edgar Leroy. It is documented that Hans Reiter was one of a number of University professors who signed an oath of allegiance to Adolf Hitler in 1932. For socio-ethical reasons and for clinical utility, Reiter's syndrome is now known as reactive arthritis.
A young woman in her early 30s presented with a right thyroid mass and progressive hoarseness due to a right vocal cord palsy. The preoperative fine-needle aspiration cytology was classified as Bethesda V and she underwent a total thyroidectomy and neck dissection. Intraoperatively, the thyroid mass was adherent to the oesophagus, trachea and encasing the right recurrent laryngeal nerve which was sacrificed. Final histopathology diagnosed a rare subtype of thyroid cancer known as intrathyroidal thymic carcinoma (ITC). She was then sent for adjuvant radiotherapy after a multidisciplinary tumour board discussion. This case report highlights the difficulty in preoperative diagnosis of ITC and the importance of immunohistochemical staining in clinching the diagnosis. In view of its rarity, there have been no published consensus on the treatment of ITC, hence we would like to share some learning points through a comprehensive literature review.
Sports-related concussions (SRCs) are a growing health concern, since they may lead to persistent symptoms and, particularly if repeated, to e.g. depression, accelerated dementia onset, and development of chronic traumatic encephalopathy. Here, we addressed the hypotheses that immediate controlled head- and neck cooling could hasten return-to-play in a Swedish cohort of concussed professional ice hockey players. Over three seasons, 15 teams used either immediate head- and neck cooling or standard management for SRC. All players followed the same return-to-play management protocol. Using a baseline questionnaire, no difference in the number of previous SRCs between groups was observed. In total, 92 SRCs were recorded. Eleven players did not complete the study protocol, and thus 81 players were included. Of these, 29 were treated by immediate selective head- and neck cooling for ≥ 30 min, and 52 controls received standard acute SRC management.
Endotracheal pressure with different cuff shapes can result in different cuff pressure change after head positional change. In this study, 52 patients underwent middle ear surgery with general anesthesia were randomly allocated to two group; patients were intubated with taper guard cuffed tube or cylindrical shaped cuffed tube. Anesthesia was maintained with sevoflurane with air/O2 and remifentanil. The cuff pressure was initially set at 24 centimeters of water in the neural head position and was measured after the change to the 45 degree head rotation. In addition, sore throat, hoarseness , dysphagia and cough were recorded 0, 6, 12, 24 hr after surgery. The change of cuff pressure was compared between two groups. The side effects associated with tube were compared between two groups.
The IRON-PATH II Project is a pre-clinical and clinical study designed as a multicenter, prospective, observational (non-interventional), investigator initiated study. The total number of patients to be recruited will be 210 (80 patients without ID and 130 patients with ID). Patients will be recruited during 12 months in 7 centers across Spain and Portugal and followed for a fixed period of 12 months. The primary objective of the clinical study is to define pathways associated with systemic and tissue ID in HF patients compared with non-ID HF patients and explore the change in the patterns of pathway activation/suppression after irons status normalization in ID patients with intravenous iron treatment using an integrative omics and systems biology approach including whole-genome analysis of gene expression (transcriptome), protein synthesis (proteomics) and metabolic characterization (metabolomics) from blood samples. Key secondary objectives will include changes in patient-reported outcomes (PROMs) such as QoL, patient-reported experience measures (PREMs), the occurrence of events, among others between those with and without ID. The aims of the pre-clinical study is to confirm previous findings of the IRONPATH I study and to explore in vitro interventions in cardiac cells models with iron deficiency.
Acute Hemodynamic Effects

Acute intravenous infusions of FLOLAN for up to 15 minutes in patients with idiopathic or heritable PAH or PAH/SSD produce dose‑related increases in cardiac index (CI) and stroke volume (SV) and dose‑related decreases in pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and mean systemic arterial pressure (SAPm). The effects of FLOLAN on mean pulmonary artery pressure (PAPm) were variable and minor.

In humans, hemodynamic changes due to epoprostenol (e.g., increased heart rate, facial flushing) returned to baseline within 10 minutes of termination of 60-minute infusions of 1 to 16 ng/kg/min. This pharmacodynamic behavior is consistent with a short in vivo half-life and rapid clearance in humans, as suggested by the results of animal and in vitro studies.

In animals, the vasodilatory effects reduce right- and left-ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally-mediated bradycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.

Drug Interaction Studies

Additional reductions in blood pressure may occur when FLOLAN is administered with diuretics, antihypertensive agents, or other vasodilators.

When other antiplatelet agents or anticoagulants are used concomitantly, there is a potential for FLOLAN to increase the risk of bleeding. However, patients receiving infusions of FLOLAN in clinical trials were maintained on anticoagulants without evidence of increased bleeding.
Hydration status plays a key role in healthy ageing, and it is potentially affected by several factors, including drug consumption. However, research on this issue to date is scarce, especially in highly vulnerable groups, such as the elderly. We aimed to study the relationship linking hydration status, analysed by means of a validated questionnaire, 24 h urine analysis, body composition assessment, and drug consumption in a sample of old adults. A total of 144 elders were included in the study. Cardiovascular drug consumption was significantly associated with a lower water intake in men (β = -0.282, p = 0.029). Moreover, urinary analysis revealed that total drug intake as well as the consumption of diuretics and cardiovascular drugs were associated with poorer hydration status, whereas genito-urinary drugs were associated with an opposite effect, and these results were confirmed in terms of body composition. Hence, total drug consumption (β = -0.205), diuretic (β = -0.408), cardiovascular (β = -0.297), and genito-urinary drugs (β = 0.298) were significantly associated (p < 0.05) with total body water. The obtained results confirmed the impact of chronic treatment with certain drugs on hydration status. Nutritional interventions may be of great interest in certain population groups in order to prevent complications due to altered hydration status.
OBJECTIVE: Obstructive sleep apnea is closely related to oxidative stress. 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) can scavenge reactive oxygen species (ROS) and ameliorate oxidative damage in the body. The mechanism by which Tempol alleviates chronic intermittent hypoxia-induced lung injury has rarely been reported. This study aimed to confirm the molecular mechanism by which Tempol alleviates lung injury.
METHODS: The levels of miR-212-5p and Sirtuin 6 (SIRT6) in injured lungs were analyzed using bioinformatics. In vitro, intermittent hypoxia (IH) treatment induced hypoxia in BEAS-2B cells and we established a model of chronic intermittent hypoxia (CIH) in mouse using a programmed hypoxia chamber. We used HE staining to observe the morphology of lung tissue, and the changes in lung fibers were observed by Masson staining. The levels of inflammatory factors in mouse serum were detected by ELISA, and the levels of the oxidative stress indicators GSH, MDA, SOD and ROS were detected using commercially available kits. Moreover, a real-time qPCR assay was used to detect miR-212-5p expression, and Western blotting was used to detect the levels of SIRT6, HIF-1α and apoptosis-related proteins. CCK-8 was used to detect cell proliferation. Subsequently, we used flow cytometry to detect cell apoptosis. Dual-luciferase gene reporters determine the on-target binding relationship of miR-212-5p and SIRT6.
RESULTS: SIRT6 was highly expressed in CIH-induced lung injury, as shown by bioinformatics analysis; however, miR-212-5p expression was decreased. Tempol promoted miR-212-5p expression, and the levels of SIRT6 and HIF-1α were inhibited. In BEAS-2B cells, Tempol also increased proliferation, inhibited apoptosis and inhibited oxidative stress in BEAS-2B cells under IH conditions. In BEAS-2B cells, these effects of Tempol were reversed after transfection with an miR-212-5p inhibitor. miR-212-5p targeted and negatively regulated the level of SIRT6 and overexpression of SIRT6 effectively reversed the enhanced influence of the miR-212-5p mimic on Tempol's antioxidant activity. Tempol effectively ameliorated lung injury in CIH mice and inhibited collagen deposition and inflammatory cell infiltration. Likewise, the therapeutic effect of Tempol could be effectively reversed by interference with the miR-212-5p inhibitor.
CONCLUSION: Inhibition of the SIRT6-HIF-1α signaling pathway could promote the effect of Tempol by upregulating the level of miR-212-5p, thereby alleviating the occurrence of lung injury and providing a new underlying target for the treatment of lung injury.
VP-16 is an antitumor agent. Previous problems with VP-16 include the route of administration and the toxicities. VP-16 has been given intravenously for 3 consecutive days in a 21-day cycle for lung cancer and testicular cancer. VP-16 has also been used in lymphoma therapy. Oral VP-16 would eliminate the need for an intravenous catheter and so a patient could avoid the pain, inconvenience, and potential complications associated with medications administered intravenously. The relative ease of outpatient administration and the potentially significant antitumor activity of oral VP-16 motivates this study. The possibility of weekly drug administration is the other focus of this study.

Four patients are entered at each dose level starting with level 1. Patients are not entered into the next higher dose level until at least two patients at the previous dose level have completed at least 3 weeks of therapy with grade 2 or less maximum tolerated dose-defining toxicities. Treatment is repeated weekly for 52 weeks until either a grade 3 or 4 toxicity occurs, or until a patient shows a complete response or progressive disease. Patients with a complete response are continued on drug for 4 additional weeks from the time that complete response is first documented. Patients with progressive disease are withdrawn from study. Patients with partial response or stable disease continue until either unacceptable toxicity occurs or a complete response or progression of disease is reached.
FIELD: organic chemistry, pharmacy, cosmetics. SUBSTANCE: invention relates to new bicyclic aromatic compounds of the general formula (I) where values R 1 ,R 2 ,R 3 , X and Ar are given in p. 1 of the invention claim. Compounds show activity with respect to cellular differentiation and proliferation and can be used in treatment of patients with dermatological sicknesses associated with keratinization damage. Compounds are used by topical or systemic route. Compounds of the formula (I) can be used for body hygiene and care for hair. Invention describes a pharmaceutical composition containing the above indicated compounds and using for the same purposes as compounds of the formula (I). EFFECT: enhanced effectiveness of compounds and compositions. 16 cl, 3 dwg, 27 ex
Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.