anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Dysregulation of Wingless and Int-1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium-conditioned media (OAS-CM) was collected after incubating synovium from human end-stage OA joints for 24 h in medium. Cytokine levels in the OAS-CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS-CM or 1 ng/mL Interleukin-1β (IL-1β). Effects on expression levels of Wnt signaling members were determined by reverse transcription-quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor α, and granulocyte-macrophage colony-stimulating factor positively correlated with each other. MS increased noncanonical WNT5A and FOS expression. In contrast, these genes were downregulated upon stimulation with OAS-CM or IL-1β. Furthermore, Wnt inhibitors DKK1 and FRZB decreased in response to OAS-CM or IL-1β exposure. Finally, expression of WNT5A in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.
Presepsin (P-SEP) is a specific biomarker for sepsis. Monocytes produce P-SEP by phagocytosing neutrophil extracellular traps (NETs). Herein, we investigated whether M1 macrophages (M1 MΦs) are the primary producers of P-SEP after NET phagocytosis. We co-cultured M1 MΦs and NETs from healthy participants, measured P-SEP levels in the culture medium supernatant, and detected P-SEP using western blotting. When NETs were co-cultured with M1 MΦs, the P-SEP level of the culture supernatant was high. Notably, we demonstrated, for the first time, the intracellular kinetics of P-SEP production by M1 MΦs via NET phagocytosis: M1 MΦs produced P-SEP intracellularly 15 min after NET phagocytosis and then released it extracellularly. In a sepsis mouse model, the blood NET ratio and P-SEP levels, detected using ELISA, were significantly increased (p < 0.0001). Intracellular P-SEP analysis via flow cytometry demonstrated that lung, liver, and kidney MΦs produced large amounts of P-SEP. Therefore, we identified these organs as the origin of M1 MΦs that produce P-SEP during sepsis. Our data indicate that the P-SEP level reflects the trend of NETs, suggesting that monitoring P-SEP can be used to both assess NET-induced organ damage in the lungs, liver, and kidneys during sepsis and determine treatment efficacy.
Provided herein are methods for inhibiting osteolysis or treating osteoporosis in a subject in need thereof, the method including administering to the subject at least one RON inhibitor. The osteolysis may be caused by a condition selected from the group consisting of cancer, inflammation, and cyst. The condition may include a bone tumor or a tumor located in bone. The subject may have been diagnosed with bone cancer. The inhibitor may be ASLAN002. The inhibitor may be OSI-296. The inhibitor may be selective or specific for RON. The inhibitor may not depend on the function of RANKL or TGFβ.
Patients receive abemaciclib PO BID on days 1-28 and 5-FU IV over 46 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study and may additionally undergo a tissue biopsy before treatment and on cycle 1 day 16.
Group weight loss program plus use of the Senseware Armband - Participants in this group attended a 14-session group weight loss program administered by trained facilitators plus 6 one-on-one telephone sessions with a facilitator and wore a SenseWear Armband. The SenseWear system includes the Armband, a real-time display device, and a personalized Weight Management Solutions web account. Participants received training in using the Armband and were asked to wear it at least 16 hours per day.
The invention relates to novel N-alkylated aminoalcohols of the formula    <IMAGE>  (I)  in which Ar is a radical of aromatic character which is unsubstituted or substituted by hydroxyl, n has the values nought or 1 and Alk is an alkylene radical having 2 to 5 carbon atoms and the nitrogen atom and the oxygen atom or, if n is nought, the salicylamide radical are separated from one another by at least two carbon atoms in the straight-chain, and their salts. The main action of the novel compounds consists in a stimulation of cardiac  beta -receptors; the compounds also effect a blockage of adrenergic  alpha -receptors and a lowering in the blood pressure. They can therefore be used as  beta -stimulators, especially as agents having a positively inotropic action for the treatment of cardiac insufficiency. Compounds of the formula I in which Ar is phenyl, unsubstituted or substituted by 1 or 2 hydroxyl groups, Alk is an alkylene radical having 2 to 4 carbon atoms, n has the value 1, and the nitrogen atom and the oxygen atom are separated from one another by at least 2 carbon atoms in the straight-chain, or salts thereof, exhibit effects on the central nervous system, which are reflected for example in the suppression of the symptoms of impaired sympathetic functions and in the suppression of lack of initiative. Such compounds of the formula I therefore can be used for the treatment of reactive or endogenic states of depression of varying degrees of severity, and also for the treatment of neurotic or other psychic disturbances involving loss of initiative and depressive disorders. Such compounds can also be used for the short-term treatment of post-partum or postoperative depression, or of depression of different origin. Such compounds of the formula I can be used on their own or in combination with other antidepressants.
A mutant prourokinase plasminogen activator (M5) was developed to make prouPA less subject to spontaneous activation during fibrinolysis. C1-inhibitor complexes with tcM5. The effect of C1-inhibitor on fibrinolysis and fibrinogenolysis by M5 was determined. Supplemental C1-inhibitor restores the stability of M5 but not that of prouPA. Clot lysis by M5 with supplemental C1-inhibitor showed no attenuation of the rate of fibrinolysis, whereas fibrinogenolysis was prevented by C1-inhibitor. Due to higher dose tolerance of M5 with C1-inhibitor, the rate of fibrin-specific lysis reached that achievable by nonspecific fibrinolysis without inhibitor. Plasma C1-inhibitor stabilized M5 in plasma by inhibiting tcM5 and thereby non-specific plasminogen activation. At the same time, fibrin-specific plasminogen activation remained unimpaired. This unusual dissociation of effects has significant implications for improving the safety and efficacy of fibrinolysis. Methods of reducing bleeding and non-specific plasminogen activation during fibrinolysis by administering M5 along with exogenous C1-inhibitor are disclosed.
Participants in the Learning Skills Together program will begin their participation with a one-on-one phone call with an interventionist, who will ensure the participant is prepared to to attend the group sessions (e.g., familiar with videoconference technology) and will help the participant to set individual goals. The caregiver participant will then attend 4, group-based sessions lasting approximately 1.5 hours each, to learn about common complex care tasks managed by family caregivers to someone with mid-stage Alzheimer's disease, such as managing behavioral symptoms of dementia, incontinence, nutrition, transferring, medication management, and more. Sessions will integrate interactive activities, such as videos, case studies, and discussions. Approximately four weeks later, caregivers will be asked to attend a group reflection session to discuss application of what was learned and progress in meeting individual goals.
The present invention belongs to field of biology and medicine, and especially relates to a novel antibiotic comprising a mimetic antibody, its preparation methods and uses thereof. The novel antibiotic comprising comprising an antibody mimetic and a colicin,or comprising an antibody mimetic and a channel-forming domain of a colicin, the antibody mimetic covalently bonded to the carboxyl end of the polypeptide of the colicin or the channel-forming domain of the colicin, wherein the colicin is selected from a group consisting of colicin E1, Ia, Ib, A, B, N; wherein said antibody mimetic being yielded by fusing two complementarity determining regions (CDRs), V H CDR 1 ) and V L CDR through a cognate framework region (V H FR 2 ) of an immunoglobulin; wherein the immunoglobulin specifically recognizes bacterium porins. Its antibacterial ability is a thousandfold powerful than normal antibiotics. Due to its unique action mechanism, drug resistance resulted in mutation can hardly be acquired by pathogenic bacteria. And the antibiotic will not hurt normal human cells when it kills pathogenic bacteria. Therefore, it can be used for manufacturing antibacterial medicament of killing Diplococcus intracellularis, vancomycin-resistant enterococci, Methicillin-resistant Staphylococcus aureus, or multidrug resistant Pseudomonas aeruginosa.
Pyoderma gangrenosum (PG) is an uncommon dermatosis that consists of nodules and pustules that ulcerate. PG can occur anywhere on the body. Lesions often progress in size and may be multiple. There is no universally accepted treatment for PG. In mild disease, therapy consists of local wound care and topical or intralesional corticosteroids. For more severe disease, systemic agents are necessary. Systemic corticosteroids are often effective, but large doses are required leading to serious long-term side effects. Other immunosuppressives have been reported to be successful in individual case reports and small case series. However, they too are associated with significant toxicities.

Infliximab is an antibody directed against TNF-α. It had been used in success for treatment of PG. Adalimumab (Humira) is a fully human antibody directed against TNF-α. Given that adalimumab has the same target as infliximab, one would expect that adalimumab may also be effective in the treatment of PG. Treatment with adalimumab may be advantageous over infliximab because it can be given at home, whereas infliximab is delivered intravenously in the office. Additionally, because adalimumab is fully human, patients would be less likely to form antibodies against the medication. Purpose of this study is to determine the safety and efficacy of Humira in the treatment of pyoderma gangrenosum.
Heparin-induced thrombocytopenia (HIT) is rare, affecting fewer than 1 in 1500 hospital admissions. Despite the increasing adoption of new therapies in HIT, such as direct oral anticoagulants and pooled immunoglobulins, there is limited high-quality evidence to guide clinicians. Numerous uncommon presentations of HIT and HIT-like entities have recently been recognized, and a harmonized approach to their classification is required to study them better. We present the results of an international survey of opinions from experts and practitioners in the field of platelet immunology regarding the role of direct oral anticoagulants in HIT, novel definitions of subclassifications of HIT-like platelet factor 4 immune conditions (spontaneous autoimmune HIT, persistent autoimmune HIT, and treatment-refractory HIT), and the role for intravenous immunoglobulins in the treatment paradigm of HIT and these HIT-like conditions. From 102 survey responses, there was broad acceptance of rivaroxaban (74.5%) and apixaban (73.5%) even before platelet recovery, as well as for intravenous immunoglobulin in the management of spontaneous (85.6%), persistent (83.7%), and treatment-refractory HIT (87.4%). With this mandate for harmonizing terminologies and treatment approaches in special situations without robust clinical data owing to their rarity, we plan to conduct a robust survey, establish international consensus, and draft management guidelines for HIT and platelet factor 4 immune diseases in the near future.
Subjects in the group A will be given HQP1351 after fasting meal on Day 1. Then after a seven-day of cleaning time, subjects in the group A will be given HQP1351 after 30 minutes of high-fat meal on Day 8.
180 primary health care facilities in Nigeria are participating in this study. In one arm of this trial, 60 of the participating facilities are randomly assigned a physician (in addition to existing clinic staff); in a second arm, 60 facilities are randomly assigned an additional mid-level provider (of similar training to existing providers); and the third arm consists of facilities that receive no additional providers (the control group). Assigned providers will practice in those facilities for approximately one year. Stratifying by treatment arm, the investigators further randomize 10-15 enumeration areas within each facility catchment (service) area to either a Conditional Cash Transfer (CCT) arm or to a control arm. The cash transfer is intended for currently pregnant women in those enumeration areas and is conditioned upon attending four antenatal care visits, giving birth in the facility, and attending at least one postnatal visit.

To measure the effects of the interventions the investigators randomly sample 15 households in each facility catchment area and enroll all currently pregnant women within the study enumeration areas. Women at an advanced stage of pregnancy - third trimester - are excluded because such women will not be exposed to the intervention for the majority of their pregnancy. All household members are interviewed at baseline, midline (6 months later) and endline (12 months later) to collect information about health-seeking behavior and health status. Pregnant women are also interviewed at baseline and approximately 1-3 months after birth to collect information about health care utilization and birth outcomes. Additionally the investigators collect data from the participating health facilities and providers. Using a combination of provider surveys, clinical vignettes, direct clinical observation, and patient exit interviews the investigators examine the effects of the intervention on service delivery and quality.
For individuals living with a chronic illness who require use of long-term medications, adherence is a vital aspect of successful symptom management and outcomes. This study investigated the effect of a smartphone app on adherence, self-efficacy, knowledge, and medication social support in a medically underserved adult population with various chronic illnesses. Participants were randomized to a group who used the app for one month or a control group provided with a printed medication list. Compared to the control group, participants receiving the intervention had significantly greater medication adherence (Cohen's d = -0.52, p = .014) and medication self-efficacy (Cohen's d = 0.43, p = .035). No significant effects were observed related to knowledge or social support. The findings suggest use of the app could positively impact chronic disease management in a medically underserved population in the United States.
The ABPA is responsible for pulmonary exacerbations in chronic bronchial diseases. The treatment of ABPA consists in systemic corticosteroids and anti fungal therapy, which can have severe side effects. The diagnosis is difficult, based on several but non-specific characteristics. One of the radiologic abnormalities on CTscan could be more specific : high attenuation in impacted mucus, but this sign is found in about 30% of cases. Recent articles and investigators experience seem to demonstrate that MRI could provide an interesting tool for ABPA diagnosis, studying the signal of bronchial impactions. The aim of the study is to describe the MRI characteristics of patients with ABPA and compare the results with those obtained by CTscan, and in order to determine if there is a specific signal of impaction in ABPA.
Dosage must be individualized based on severity of arrhythmia and response. Use the lowest effective dose. Obtain baseline chest x-ray, pulmonary function tests, thyroid function tests, and liver aminotransferases. Correct hypokalemia, hypomagnesemia, and hypocalcemia before initiating treatment.

Recommended Dosage:

Initiate treatment with a loading dose of 800 to 1600 mg/day until initial therapeutic response occurs (usually 1 to 3 weeks). Once adequate arrhythmia control is achieved, or if side effects become prominent, reduce Pacerone tablet dose to 600 to 800 mg/day for one month and then to the maintenance dose, usually 400 mg/day.

Administration:

Administer Pacerone tablets consistently with regard to meals [see Clinical Pharmacology (12.3)]. Administration of Pacerone tablets in divided doses with meals is suggested for total daily doses of 1000 mg or higher, or when gastrointestinal intolerance occurs.
PURPOSE:To obtain a first liquid of a cold-wave lotion effective in suppressing the damage of hair and giving excellent feeling and luster to the hair by using an amino-modified silicone and one or more components selected from hydrolyzed protein, polypeptide and their derivatives as essential components. CONSTITUTION:The objective liquid can be produced by using (A) one or more components selected from hydrolyzed protein, polypeptide and their derivatives and having an average molecular weight of 200-4,000 and (B) an amino-modified silicone of formula (X is 10-500; Y is 1-30; n is 1-10; m is 1-10) as essential components and properly compounding the components with perfume, preservative, amine, thickener. etc. The component A is e.g. hydrolyzed product of a protein such as keratin, collagen or silk or its derivative or a polypeptide purified from the hydrolyzed product of the protein. The amounts of the components A and B are 0.1-10wt.% and 0.1-5.0wt.%, respectively.
Patients that are mechanically ventilated for more than 24 hours until the weaning process can be started. At the beginning of the weaning process the PEEP will be adjusted at a value equal with the PEEP during BiPAP (Group 1) and Pmean during BiPAP (Group 2) During controlled mechanical ventilation all patients will be for 5 minutes with FiO2 - 100% ventilated. The PaO2/FiO2 after 5 minutes ventilation with 100% oxygen will be compared with the PaO2/FiO2 during ventilation with 30% oxygen.
NEW MATERIAL:A proteinous substance having a main component molecular weight of 15,000-20,000 and obtained by physically disintegrating toxoplasma, subjecting the resultant water-soluble component to ultra-high-speed centrifugal separation and separating from the supernatant liquid. USE:An antitumor agent exhibiting remarkable antitumor activity even against allogenic tumor, isogenic tumor and autologous tumor. A synergistic effect can be achieved by the combined use with an immuno-activating substance ovioactin. It is easily soluble in water in contrast with an IFN-inducing agent disclosed in Japanese Patent Applitation No.59-27832. PREPARATION:Toxoplasma (e.g. Toxoplasma gondii) is diluted with distilled water and disintegrated by ultrasonic treatment at 4-15 deg.C for 3-5min. The insoluble components in the disintegrated product is optionally removed by centrifugal separation (e.g. at 16,000 G and 4 deg.C for 60min) and the product is converted to isotonic solution with NaCl and subjected to ultra-high-speed centrifugation at >=100,000 G (e.g. at 4 deg.C for 120min). The objective proteinous substance containing a main component having a molecular weight of 15,000-20,000 can be obtained as the supernatant liquid.
NEW MATERIAL:A gamma-globulin complex wherein adriamycin or daunomycin is bonded through a spacer to gamma-globulin. EXAMPLE:An adriamycin-dextran-gamma-globulin complex. USE:A carcinostatic agent. Having a more excellent therapeutic index (toxicic amount/effective amount) than administration of a drug alone, having no problem of antigenicity. The complex is efficiently accumulated in a cancerous cell, so it has low toxicity to a normal cell, and useful as a carcinostatic agent. PREPARATION:Firstly, a spacer such as a dextran oxide shown by the formula is reacted with daunomycin or adriamycin preferably in a ratio of 1:2-200 (molecules), to give a complex of dextran-substance having carcinostatic action. Gamma-globulin in an amount to make 0.1-3w/v% final concentration is added to a solution of 1-30w/v% of the complex, to give a novel gamma-globulin complex.
OBJECTIVE: To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying molecular mechanisms.
METHODS: Cerebral IRI was induced in male Sprague-Dawley (SD) rats using middle cerebral artery occlusion (MCAO). The effects of PTX on cerebral ischaemia-reperfusion brain samples were detected through neurological deficit score, staining and electron microscopy; levels of ferroptosis biomarkers from brain samples were detected using kits. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), transferrin receptor protein 1, divalent metal transporter 1, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting.
RESULTS: Pre-treatment with PTX was found to improve neurological function, evidenced by reduced neurological deficit scores, decreased infarct volume and alleviated pathological features post-MCAO. This improvement was accompanied by reduced lipid peroxidation levels and mitigated mitochondrial damage. Notably, PTX's inhibitory effect on ferroptosis was characterised by enhanced Nrf2 nuclear translocation and regulation of ferroptosis-related proteins. Moreover, inhibition of Nrf2 using ML385 (an Nrf2-specific inhibitor) reversed PTX's neuroprotective effect on MCAO-induced ferroptosis via the SLC7A11/GPX4 signalling pathway.
CONCLUSIONS: Ferroptosis is evident following cerebral ischaemia-reperfusion in rats. Pentoxifylline confers protection against IRI in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signalling pathway.
Alprazolam is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A). Most of the interactions that have been documented with alprazolam are with drugs that inhibit or induce CYP3A4.

Compounds that are potent inhibitors of CYP3A would be expected to increase plasma alprazolam concentrations. Drug products that have been studied in vivo, along with their effect on increasing alprazolam AUC, are as follows: ketoconazole, 3.98 fold; itraconazole, 2.7 fold; nefazodone, 1.98 fold; fluvoxamine, 1.96 fold; and erythromycin, 1.61 fold (see Contraindications, Warnings, and Precautions–Drug Interactions).

CYP3A inducers would be expected to decrease alprazolam concentrations and this has been observed in vivo. The oral clearance of alprazolam (given in a 0.8 mg single dose) was increased from 0.9±0.21 mL/min/kg to 2.13±0.54 mL/min/kg and the elimination t1/2 was shortened (from 17.1±4.9 to 7.7±1.7 h) following administration of 300 mg/day carbamazepine for 10 days (see Precautions–Drug Interactions). However, the carbamazepine dose used in this study was fairly low compared to the recommended doses (1000 to 1200 mg/day); the effect at usual carbamazepine doses is unknown.

The ability of alprazolam to induce human hepatic enzyme systems has not yet been determined. However, this is not a property of benzodiazepines in general. Further, alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally.