anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
T-cell-directed cancer therapies such as T-cell-engaging bispecifics (TCBs) are commonly associated with cytokine release syndrome and associated clinical signs that can limit their tolerability and therapeutic benefit. Strategies for reducing cytokine release are therefore needed. Here, we report on studies performed in cynomolgus monkeys to test different approaches for mitigating cytokine release with TCBs. A "priming dose" as well as subcutaneous dosing reduced cytokine release compared with intravenous dosing but did not affect the intended T-cell response to the bispecific. As another strategy, cytokines or cytokine responses were blocked with an anti-IL-6 antibody, dexamethasone, or a JAK1/TYK2-selective inhibitor, and the effects on toxicity as well as T-cell responses to a TCB were evaluated. The JAK1/TYK2 inhibitor and dexamethasone prevented CRS-associated clinical signs on the day of TCB administration, but the anti-IL-6 had little effect. All interventions allowed for functional T-cell responses and expected damage to target-bearing tissues, but the JAK1/TYK2 inhibitor prevented the upregulation of activation markers on T cells, suggesting the potential for suppression of T-cell responses. Our results suggest that short-term prophylactic dexamethasone treatment may be an effective option for blocking cytokine responses without affecting desired T-cell responses to TCBs.
PURPOSE: A hair treatment composition is provided to ensure hair conditioning effects and to maintain hair style. CONSTITUTION: A hair treatment composition contains 0.01-10 wt% of reducing sugar as an active ingredient. The reducing sugar is selected from a group consisting of xylose, glucose, fructose, galactose, lactose, and maltose. The composition further contains one or more kinds selected from amino acids and proteins. A method for hair treatment comprises: a step of applying the hair treatment composition on hair; and a step of heating at 60-200 deg. C.
Treatment will include a 1.5-hour intervention session combined with daily text-messaging for up to 1 week pre-quit and 4 weeks post-quit. The intervention includes: mindful breathing, visualization, and identification and thinking about goals and priorities inconsistent with smoking. During the text-messaging phase, elements of the intervention discussed during the in-person session will be reinforced. Participants will be provided transdermal nicotine patches (TNP). TNP are a safe and effective approach to nicotine replacement when an individual attempts to stop smoking and are safe for use without prescription. Participants will begin the regimen on the scheduled quit date with an initial dose of 21 mg (4 weeks), followed by 14 mg (2 weeks), and 7 mg (2 weeks). Alterations to dosing will be allowed when appropriate and consistent with manufacturer's recommendations. While TNP will be offered to all participants, they can decline or discontinue use of TNP at any time.
Cardiovascular disease (CVD) has emerged as an increasingly important cause of morbidity and mortality among people living with HIV (PLWHIV). Now that HIV is considered a manageable chronic disease, the identification and treatment of comorbid medical conditions including CVD are increasingly the focus of research and clinical attention. What is missing, however, is yet another critical component of care for PLWHIV: integrated care for histories of trauma. Experiences of trauma increase the likelihood of HIV infection as well as CVD risk, yet health care for PLWHIV is rarely coordinated to address these three intersecting issues of HIV, CVD, and trauma, particularly among those disproportionately affected by HIV, i.e., ethnic minority patients. Histories of trauma among PLWHIV are associated with inconsistent treatment adherence and non-adherence, and trauma history alone is associated with poor CVD outcomes. Failure to address trauma poses significant barriers to the adoption of CVD risk strategies among PLWHIV. Health systems that coordinate and integrate care across HIV and chronic conditions such as CVD may provide the infrastructure needed to address the complex interplay of these conditions and their therapies. The investigators have designed a novel blended, culturally-congruent, evidence-informed care model, "Healing our Minds and Bodies" (HHMB), to address patients' trauma histories and barriers to care, and to prepare patients to engage in CVD risk reduction. Recognizing the need to ensure that PLWHIV receive CVD guideline-concordant care, the investigators have also identified implementation strategies to prepare providers and clinics for addressing CVD risk among their HIV-positive patients. Therefore, using a hybrid type II effectiveness/implementation study design, the goal of this study is to increase both patient and organizational readiness to address trauma and CVD risk among PLWHIV. The Specific Aims are: (1) to assess and enhance organizational readiness for addressing trauma and CVD risk among ethnic minority PLWHIV; specifically, a phased approach will drive the use of implementation strategies designed to educate, monitor, and support providers and staff in adhering to CVD care guidelines; (2) using mixed methods, to (a) evaluate the use and effectiveness of implementation strategies over time, and (b) identify barriers and facilitators to organizational adoption of guidelines, provider adherence to guidelines, feasibility, and sustainability; and (3) To evaluate the effect of HHMB on cognitive-behavioral, emotional, and clinical outcomes among 260 African American and Latino PLWHIV. The investigators will use the Replicating Effective Programs (REP) framework to guide the use of implementation strategies and the tailoring of the HHMB intervention within our participating implementation settings, and the Consolidated Framework for Implementation Research to guide the evaluation analyses.
BACKGROUND: The lungs are highly susceptible to damage during sepsis, with severe lung injury potentially progressing to acute respiratory distress syndrome and even fatal sepsis. Effective efferocytosis of apoptotic cells is crucial in alleviating inflammation and tissue injury.
METHODS: We established a septic lung injury mouse model via intraperitoneal injection of lipopolysaccharide. Lung injury was assessed by histology, immunofluorescence, neutrophil immunohistochemistry staining, and cytokine detection. We extracted alveolar macrophages by bronchoalveolar lavage and primary macrophages from mouse bone marrow to investigate the regulatory effects of Dexmedetomidine (DEX) on efferocytosis. We further validated the molecular mechanisms underlying the regulation of macrophage efferocytosis by DEX through knockdown of AXL expression. Additionally, we examined the efferocytic ability of monocytes isolated from patients.
RESULTS: We discovered that DEX treatment effectively alleviated pulmonary injury and inflammation. Lipopolysaccharide reduced macrophage efferocytosis and AXL expression which were reversed by DEX. We also found DEX inhibited the increased activation of A Disintegrin And Metalloproteinase 10 (ADAM10) and the production of soluble AXL. Moreover, our findings demonstrated that DEX decreased the elevated ROS production linked to higher ADAM10 activation. Blocking AXL negated DEX's benefits on efferocytosis and lung protection. Efferocytosis in monocytes from septic lung injury patients was notably lower than in healthy individuals.
CONCLUSION: Our findings demonstrated that DEX treatment effectively reduces septic lung injury by promoting macrophage efferocytosis through ROS/ADAM10/AXL signaling pathwway.
PURPOSE:To obtain a suppressant for hypoglycemia, containing conduritol A or its derivative as an active ingredient, capable of reducing the load on insulin secretion and useful for treating diabetes. CONSTITUTION:This suppressant for hypoglycemia contains 1-90wt.% conduritol A expressed by formula I or its derivative expressed by formula II (R1 and R2 each is H, acetyl or a lower alkyl, with the proviso that both R1 and R2 are not simultaneously H) as an active ingredient. The compounds expressed by formulas I and II are capable of suppressing a sudden rise in blood sugar level caused in ingesting sugar at meal, etc., and reducing the load on insulin secretion. The suppressant can be prepared into a dosage form for oral or enteral administration. The daily dose thereof for an adult is preferably 10-3000mg internally used in the case of the oral administration. The compounds expressed by formulas I and II can be obtained by carrying out the extraction and purification thereof from a dried leaf of Gymnema sylvestre R. Br. or dried powder of bark of Marsdenia condurango Richenbach fil or according to a well-known chemical synthetic method.
Patients receive tiragolumab IV over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo blood sample collection on study.
PURPOSE: To develop a quality appraisal tool for the assessment of cadaveric biomechanical laboratory and other basic science biomechanical studies.
METHODS: For item identification and development, a systematic review of the literature was performed. The content validity index (CVI) was used either to include or exclude items. The content validity ratio (CVR) was used to determine content validity. Weighting was performed by each panel member; the final weight was either up- or downgraded to the closest of 5% or 10%. Face validity was scored on a Likert scale ranked from 1 to 7. Test-retest reliability was determined using the Fleiss kappa coefficient. Internal consistency was assessed with Cronbach's alpha. Concurrent criterion validity was assessed against the Quality Appraisal for Cadaveric Studies scale.
RESULTS: The final Biomechanics Objective Basic science Quality Assessment Tool (BOBQAT) score included 15 items and was shown to be valid, reliable, and consistent. Five items had a CVI of 1.0; 10 items had a CVI of 0.875. For weighting, 5 items received a weight of 10%, and 10 items a weight of 5%. CVR was 1.0 for 6 items and 0.75 for 9 items. For face validity, all items achieved a score above 5. For test-retest reliability, almost-perfect test-retest reliability was observed for 10 items, substantial agreement for 4 items, and moderate agreement for 1 item. For internal consistency, Cronbach's alpha was calculated to be 0.71. For concurrent criterion validity, Pearson's product-moment correlation was 0.56 (95% confidence interval [CI] = 0.38-0.70, P = .0001).
CONCLUSIONS: Cadaveric biomechanical and laboratory research can be quantitatively scored for quality based on the inclusion of a clear and answerable purpose, demographics, specimen condition, appropriate bone density, reproducible technique, appropriate outcome measures, appropriate loading conditions, appropriate load magnitude, cyclic loading, sample size calculation, proper statistical analysis, results consistent with methods, limitations considered, conclusions based on results, and disclosure of funding and potential conflicts.
CLINICAL RELEVANCE: Study quality assessments are important to evaluate internal and external validity and reliability and to identify methodological flaws and misleading conclusions. The BOBQAT score will help not only in the critical appraisal of cadaveric biomechanical studies but also in guiding the designs of such research endeavors.
Patients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, PET, and MRI, as well as collection of blood during screening, on study, and during follow-up. Patients also undergo a tumor biopsy during screening and on study.
PURPOSE:To improve hydrophilicity (wettability) of a sintered apatite compact and preserve the aforementioned hydrophilicity without deteriorating thereof as mush as possible by heat-treating the sintered apatite compact within at a specific temperature range. CONSTITUTION:A compact of apatite is sintered according to a conventional method and allowed to stand for an optional period just after or after the sintering. The resultant sintered apatite compact is then heat-treated at 800-900 deg.C, preferably 700-800 temperature. The heat-treating time is normally 1-4hr, preferably 2-3hr. Thereby, the hydrophilicity of the sintered apatite compact can be remarkably improved using simple operation and an implant improved in osseous adhesion is obtained. The sintered apatite compact with improved hydrophilicity by the aforementioned method is vacuum packaged and preserved to retain the hydrophilicity for a long period and preservation in a germ-free state can simultaneously be carried out.
Participants in the Treatment arm receive 2 therapy sessions on LifeSteps and sexual decision-making, as well at 8 sessions of Cognitive Behavioral Therapy for Trauma and Self-Care (CBT-TSC). Participants then participate in 3-, 6-, and 9-month follow-up assessments.
Schroth Best Practice Exercises and Cheneau braces. There were 18 sessions, each lasting 90 minutes, a total of 6 weeks for the exercise training.
Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke. ANN NEUROL 2024;96:871-886.
Patients receive doxorubicin IV over 24 hours on days -9 to -6, cyclophosphamide IV over 2 hours on day -5, and paclitaxel IV over 24 hours on day -2. PBSC are reinfused on days -2 and 0. G-CSF is administered beginning on day 0 and continuing until blood counts recover.
Conduit arterial disease in chronic kidney disease (CKD) is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to humans with CKD stage 4-5. Parathyroid hormone (PTH) and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased, and vascular smooth muscle cell (VSMC) transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed that ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (P = 0.022). RNA-Seq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. To examine the effect of activin A signaling, some Alport mice were treated with a monoclonal Ab to activin A or an isotype-matched IgG beginning at 75 days of life until euthanasia. Treatment with the activin A antibody (Ab) did not affect cardiac oxidative phosphorylation. However, the activin A antibody was active in the skeleton, disrupting the effect of CKD to stimulate osteoclast number, eroded surfaces, and the stimulation of osteoclast-driven remodeling. The data reported here show that cardiac mitochondrial respiration is impaired in CKD in the absence of conduit arterial disease. This is the first report of the direct effect of CKD on cardiac respiration.NEW & NOTEWORTHY Heart disease is an important morbidity of chronic kidney disease (CKD). Hypertension, vascular stiffness, and vascular calcification all contribute to cardiac pathophysiology. However, cardiac function in CKD devoid of vascular disease has not been studied. Here, in an animal model of human CKD without conduit arterial disease, we analyze cardiac respiration and discover that CKD directly impairs cardiac mitochondrial function by decreasing oxidative phosphorylation. Protection of cardiac oxidative phosphorylation may be a therapeutic target in CKD.
PCT No. PCT/EP89/01092 Sec. 371 Date May 17, 1990 Sec. 102(e) Date May 17, 1990 PCT Filed Sep. 21, 1989 PCT Pub. No. WO90/04382 PCT Pub. Date May 3, 1990.The aqueous hair- and body-treatment composition having physiological and dermatological compatibility properties as well as a germ-inhibiting effect contains from 0.1 to 50 percent by weight of a surfactant or a surfactant mixture, from 0.01 to 2.0 percent by weight of sodium formate, ammonium formate, potassium formate or magnesium formate, from 0.05 to 2.0 percent by weight of a sorbic acid element selected from the group consisting of sorbic acid and salts of sorbic acid, including alkali metal salts of sorbic acid, particularly sodium sorbate, and from 0.1 to 1.5 percent by weight of phosphoric acid or an aliphatic organic acid containing from 2 to 6 carbon atoms and being free of amino and halogen substituents. A method of preserving an aqueous hair- and body-cleaning composition is also described.
Placebo stimulation is performed using the same current intensity, but only applied for 45 seconds in addition to the 10 second ramp-up and 10 second ramp-down periods. The electrode configuration and placement will be identical to the active stimulation.
PURPOSE:To provide new compounds excellent in emulsifying properties, water- holding properties and moisture-permeability and capable of, therefor, providing cosmetics or medical drugs showing a light feeling in use and excellent in affinity to the skin, promotion of percutaneous absorption of medical components, etc., when used as a cosmetics raw material or a base for an external-use medical drug. CONSTITUTION:Oil-soluble long-chain acyl acidic amino acid mono- or di-esters of the formula (X and Y are ester-formation residue of sterol. Or, one of them is ester-formation residue of sterol and the other is H, etc.; Z is carboxyl or sulfonyl; COR is 8-22C long chain acyl; In case Z is carboxyl, n is 1. In case Z is sulfonyl, n is 1 or 2), e.g. N-lauroyl-L-aspartic acid dicholesterol ester. The above-mentioned compound is recommendably produced by the azeotropic dehydration condensation method where an N-long chain acyl acidic amino acid such as N-lauroyl-L-aspartic acid and a sterol such as cholesterol are heated with stirring in the presence of an acid catalyst such as p-toluenesulfonic acid in a non-polar solvent at 70-200 deg.C for 1-10hr.
Described are methods for treating a keratinized tissue condition in a subject in need thereof. The method may include providing the subject including the keratinized tissue condition. The method may include conducting one or more treatment cycles on the keratinized tissue. Each treatment cycle may include contacting the keratinized tissue with an acid-activated gas-generating composition. Each treatment cycle may include contacting the keratinized tissue with an acid composition. Each treatment cycle may include allowing the acid composition and the acid-activated gas-generating composition to react effective to generate a gas at the keratinized tissue. The one or more treatment cycles may be effective to at least partly ameliorate the keratinized tissue condition in the subject.
Cancer survivors may experience long-term cardiovascular complications due to chemotherapeutic drugs such as doxorubicin (DOX). The exact mechanism of delayed DOX-induced cardiotoxicity has not been fully elucidated. Sex is an important risk factor for DOX-induced cardiotoxicity. In the current study, we identified sex differences in delayed DOX-induced cardiotoxicity and determined the underlying molecular determinants of the observed sexual dimorphism. Five-week-old male and female mice were administered intraperitoneal injections of DOX (4 mg/kg/week) or saline for 6 weeks. Echocardiography was performed 5 weeks after the last dose of DOX to evaluate cardiac function. Thereafter, mice were sacrificed and gene expression of markers of apoptosis, senescence, and inflammation was measured by PCR in hearts and livers. Proteomic profiling of the heart from both sexes was conducted to determine differentially expressed proteins (DEPs). Only DOX-treated male, but not female, mice demonstrated cardiac dysfunction, cardiac atrophy, and upregulated cardiac expression of Nppb and Myh7. No sex-related differences were observed in DOX-induced expression of most apoptotic, senescence, and pro-inflammatory markers. However, the gene expression of Trp53 was significantly reduced in hearts of DOX-treated female mice only. The anti-inflammatory marker Il-10 was significantly reduced in hearts of DOX-treated male mice only, while the pro-inflammatory marker Il-1α was significantly reduced in livers of DOX-treated female mice only. Gene expression of Tnf-α was reduced in hearts of both DOX-treated male and female mice. Proteomic analysis identified several DEPs after DOX treatment in a sex-specific manner, including anti-inflammatory acute phase proteins. This is the first study to assess sex-specific proteomic changes in a mouse model of delayed DOX-induced cardiotoxicity. Our proteomic analysis identified several sexually dimorphic DEPs, many of which are associated with the anti-inflammatory marker Il-10.
FIELD: organic chemistry, cosmetics, pharmacy. SUBSTANCE: invention describes biaromatic compounds of the general formula (I)   where R 1  means hydrogen atom or radical -(CH 2 ) n -OR 7 , R 2  means radical -(CH 2 ) n -OR 8 , -X-Y means a bond taken among linkages   that can be bound both from the left to the right and from to the right to the left; R 3  means chain comprising 4-8 carbon atoms substituted with one or some hydroxyl groups being hydroxyl groups can be protected as methoxy-group and, possibly and except for, they can be substituted with one or some groups of lower alkyl and/or where one or some carbon atoms in chain can be replaced with one or some oxygen or nitrogen atoms. If necessary, nitrogen atoms can be substituted with radicals of lower alkyl and/or where one or some single bonds in chain are replaced with one or some double bonds or with double and triple bond; R 3  is in benzene cycle at para- or meta-position to the bond X-Y; R 4 , R 5 , R 6 , are similar or different and mean hydrogen atom, lower alkyl, radical -OR 10 , n = 0 or 1; R 7  and R 8  mean hydrogen atom; R 9  means hydrogen atom or lower alkyl; W means oxygen, sulfur atom, radical -CH 2 - or radical NH substituted with lower alkyl; R 10  - means lower alkyl, and optical or geometrical isomers of indicated compounds. Invention describes also pharmaceutical composition eliciting agonistic activity with respect to receptors of vitamin D and cosmetic composition used for care body or hair based on indicated compounds. Invention provides the development of novel compounds that elicit selective activity with respect to proliferation and differentiation of cells. EFFECT: valuable properties of composition. 9 cl, 4 dwg, 2 tbl
Patients randomized to the standard of care arm will have a 25\[OH\] Vit D test performed, a sample taken and stored for future tests, and completion of a PHQ-9 depression survey at baseline and at study conclusion. No other contact is planned with the standard of care patients. Follow-up will be done by the querying of electronic records, which includes any 25\[OH\] Vit D testing, use of vitamin D supplementation, and outcomes.