anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Heart failure (HF) is considered one of a leading cause of cardiovascular morbidity and mortality worldwide. The association between HF and venous thromboembolism (VTE) has been reported in several studies owing to many physiological and thromboembolic risk factors. Thus, the need for extended thromboprophylaxis during the post-discharge period in HF patients has been evaluated. Most guidelines do not recommend extended thromboprophylaxis because of its uncertain benefits and increased risk of bleeding. However, recent evidence in HF patients revealed no increased risk of bleeding with extended thromboprophylaxis, which highlights the importance of identifying ideal candidates who might benefit from extended thromboprophylaxis. Several risk assessment models (RAMs) have been developed to identify patients at a high risk of VTE who would benefit from in-hospital and post-discharge prophylactic anticoagulation therapy based on the risk-benefit principle. However, their accuracy in predicting VTE is questionable, and none have a standardized approach for evaluating the risk of VTE in HF patients. In this review, we provided an overview of the incidence and pathophysiology of VTE in HF patients, a summary of guideline recommendations for VTE prevention, and a summary of studies evaluating the use of extended thromboprophylaxis, with a focus on subgroup or post-hoc analyses of HF patients. We also discussed the need to design an ideal RAM that can identify candidate patients for extended thromboprophylaxis by stratifying the risk of VTE and identifying the key risk factors for bleeding in medically ill patients, including those with HF.
Acute lung injury (ALI) caused by sepsis is one of the most common critical diseases, which is difficult to treat and has a high fatality rate. Koumine is one of the main active components of Gelsemium plants and has been confirmed to have potential for drug development; however, its therapeutic effects on ALI have not yet been studied. This study established ALI due to sepsis using cecal ligation and puncture (CLP) and assessed the therapeutic effects of koumine by measuring mouse survival rates, lung tissue pathological damage, inflammatory factors, and oxidative stress levels. Additionally, network pharmacology was utilized to explore the underlying mechanisms. The results showed that koumine inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), thereby inhibiting inflammatory response, reducing lung injury score and lung wet to dry ratio. In addition, koumine reduced oxidative stress in mice by reducing myeloperoxidase (MPO) and malondialdehyde (MDA) and increasing superoxide dismutase (SOD) content. Network pharmacology analysis showed that 52 putative targets were relevant, and SLC6A4, HTR3A, JAK2 and JAK3 were the key targets. GO and KEGG pathway enrichment analysis showed that the related mechanisms involved neuroactive ligand-receptor interaction, calcium signaling pathway, serotonergic synapses, cholinergic synapses, etc. In summary, this study confirmed the potential therapeutic effect of koumine in sepsis induced ALI, suggesting its development prospect as a novel candidate drug for ALI, and providing data support.
OBJECTIVE: Hyperexcitability is intimately linked to Alzheimer's disease (AD) pathology, but the precise timing and contributions of neuronal hyperexcitability to disease progression is unclear. Seizure induction in rodent AD models can uncover new therapeutic targets. Further, investigator-evoked seizures can directly establish how hyperexcitability and AD-associated risk factors influence neuropathological hallmarks and disease course at presymptomatic stages.
METHODS: Corneal kindling is a well-characterized preclinical epilepsy model that allows for precise control of seizure history to pair to subsequent behavioral assessments. 2-3-month-old APP/PS1, PSEN2-N141I, and transgenic control male and female mice were thus sham or corneal kindled for 2 weeks. Seizure-induced changes in glia, serotonin pathway proteins, and amyloid β levels in hippocampus and prefrontal cortex were quantified.
RESULTS: APP/PS1 females were more susceptible to corneal kindling. However, regardless of sex, APP/PS1 mice experienced extensive seizure-induced mortality versus kindled Tg- controls. PSEN2-N141I mice were not negatively affected by corneal kindling. Mortality correlated with a marked downregulation of hippocampal tryptophan hydroxylase 2 and monoamine oxidase A protein expression versus controls; these changes were not detected in PSEN2-N141I mice. Kindled APP/PS1 mice also exhibited soluble amyloid β upregulation and glial reactivity without plaque deposition.
SIGNIFICANCE: Evoked convulsive seizures and neuronal hyperexcitability in pre-symptomatic APP/PS1 mice promoted premature mortality without pathological Aβ plaque deposition, whereas PSEN2-N141I mice were unaffected. Disruptions in serotonin pathway metabolism in APP/PS1 mice was associated with increased glial reactivity without Aβ plaque deposition, demonstrating that neuronal hyperexcitability in early AD causes pathological Aβ overexpression and worsens long-term outcomes through a serotonin-related mechanism.
AIMS: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF).
METHODS AND RESULTS: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3-L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end.
CONCLUSION: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity.
REGISTRATION: ClinicalTrials.gov NCT03909919.
BACKGROUND: Intraplaque delivery of contrast has been utilized during percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) to delineate anatomy and to facilitate wire crossing. Its utility as a tool to accomplish primary crossing of CTOs has not been described or validated.
AIMS: We describe a new technique leveraging the diagnostic and therapeutic roles of intraplaque contrast injection to accomplish primary crossing of CTOs: HydroDynamic contrast Recanalization (HDR).
METHODS: HDR is an antegrade crossing method for coronary CTOs based on the synergistic use of contrast microinjections and polymer jacketed wires. We present a retrospective, first-in-man, case series utilizing HDR for CTO PCI in patients with favorable CTO anatomy (visible proximal segment and identifiable distal target). The primary outcome was procedural success. The secondary outcome was any procedural complications.
RESULTS: A total of 43 patients with 45 CTOs underwent CTO PCI with HDR. Mean patient age was 64.3 ± 11 years. The mean Japanese CTO and PROGRESS CTO scores were 2.3 ± 0.7 and 1.8 ± 0.7, respectively. CTO complexity was high, with an ambiguous or blunt cap in 34 occlusions (76%); lesion length ≥ 20 mm in 27 occlusions (60%); and moderate/heavy calcification in 36 occlusions (80%). Procedural success using HDR was 100%. There were no complications.
CONCLUSIONS: This study shows the utility of HDR in CTO PCI. HDR appears to be a safe and promising new contrast-based primary crossing technique in selected patients. This strategy warrants further evaluation in larger prospective studies.
The present invention provides preparations for efficaciously administering ginsenoside Rb 1  or its salt useful as cytoprotective agents. More particularly, the present invention provides pharmaceutical compositions comprising ginsenoside Rb 1  or its salt for inhibiting apoptosis or apoptosis-like cell death or pharmaceutical compositions comprising ginsenoside Rb 1  or its salt for promoting the expression of a cell death-inhibitory gene product Bcl-x L . Further, the present invention provides preparations for intravenous administration comprising ginsenoside Rb 1  or its salt. The above pharmaceutical compositions contain ginsenoside Rb 1  or its salt at low extracellular concentrations in lesion, preferably at 1 ng/ml or less and still preferably at 1 to 100 fg/ml. These compositions promote the expression of the cell death-inhibitory gene product Bcl-x L  and inhibit apoptosis or apoptosis-like cell death. The above preparations for intravenous administration are useful for therapy, prevention or treatment of many diseases, in particular, brain and nervous diseases.
Individuals referred for a lung resection via robotic-assisted thoracic surgery with a primary or secondary diagnosis of lung cancer. Those with a tumor \>7cm will be excluded.
The present invention relates to methods for modulating innate lymphoid cell activity, antibody drug conjugates and uses in therapy. The inventors showed in a model of murine cytomegalovirus infection, that glucocorticoid receptor expression in innate lymphoid cells plays an essential early role in regulating host protection against inflammation-induced tissue damage. Mechanistically, they demonstrated for the first time that endogenous glucocorticoids produced shortly after infection promote the expression of the immune checkpoint PD1 on the surface of natural killer cells. This glucocorticoid-PD1 pathway acts to limit the production of interferon-γ by NK cells. The modulation of the glucocorticoid-PD1 pathway in order to increase or decrease the activity of ILCs would permit to treat either cancers and infectious diseases or autoimmune and inflammatory diseases. In particular, the present invention relates to a method of modulating innate lymphoid cell activity which comprises modulating the activity of glucocorticoid receptor.
Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.
The invention discloses a polypeptide for intervening and treating cerebral hemorrhage and application thereof, wherein the polypeptide is Tat-CIRP, and the amino acid sequence of the polypeptide is shown as SEQ ID NO. 3; wherein Tat is a transmembrane structure sequence of 11 amino acids, and is specifically shown in SEQ ID NO. 1; CIRP is 15 amino acid sequences on CIRP protein sequence with highest affinity with IL-6R, and is specifically shown in SEQ ID NO. 2. The polypeptide can be specifically combined with IL-6R through specific targeting IL-6R, so that the formation of a CIRP-IL-6R compound can be competitively inhibited, JAK/STAT3 mediated inflammatory reaction can be further inhibited, the function of M1 type microglia can be inhibited, and secondary inflammatory injury after cerebral hemorrhage can be improved. The polypeptide of the invention has definite inflammation inhibition effect on cerebral hemorrhage, and provides a relatively complete experimental basis for clinical application of the polypeptide.
The United States(U.S.) has experienced higher mortality than any other nation due to COVID-19 with nearly 13.5 million cases and over 268,103 deaths. Due to the limited ability to socially distance, poor ventilation, and limited hygiene supplies, U.S. prisons and jails have observed explosive transmission of SARS-CoV-2 accounting for the 10 largest U.S. outbreaks. Because 95% of criminal justice-involved individuals reenter societyCOVID-19 transmission extends beyond those who are currently incarcerated. As justice-involved individuals reenter the community, they face high rates of homelessness, and many others live in other congregate settings such as converted hotels and halfway houses. The increased risk of SARS-CoV-2 while incarcerated coupled with the likelihood of living in congregate settings after incarceration, create conditions ripe for rapid COVID-19 transmission that will be critical to address in order to gain control of COVID-19 in the U.S. The goal of this study is to test the impact and cost-effectiveness of an intervention to mitigate SARS-CoV-2 transmission among justice-involved individuals recently released from incarceration. The investigators will conduct a randomized trial to compare the effectiveness of an onsite Point-of-Care SARS-CoV-2 testing and education intervention with community health workers (CHWs) as a central component compared to the standard of care at a community-based organization (CBO) that provides services to justice-involved individuals in New York City. The investigators will measure costs of testing, education, and navigation, and explore the cost-effectiveness of the onsite Point-of-Care intervention compared to the standard of care. The specific aims are to:1) Test the effectiveness of an onsite PoC SARS-CoV-2 intervention in a corrections-focused CBO; 2) Model the cost-effectiveness of an onsite PoC SARS-CoV-2 intervention among CJIs compared to SoC. Because testing, education, and navigation will be provided by CHWs in a culturally-sensitive environment and test results will be received in minutes (rather than days), the investigators hypothesize that O-PoC will be associated with improved testing uptake and receipt of test results, mitigation behaviors (mask wearing, hand hygiene, social distancing), and those who attend more O-PoC sessions will have better adherence to mitigation behaviors.
Chronic urticaria can be divided into 2 subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible urticaria, which has an identified specific stimulus. The annual prevalence of chronic urticaria is 0.5% to 2.3% globally. The CSU is a self-limited disorder in most cases, with an average duration of 2 to 5 years, but symptoms persist beyond 5 years in up to 30% of patients. The first line of treatment is a daily nonsedating, second-generation H1-antihistamine. The CSU guidelines recommend using oral nonsedating antihistamines up to 4 fold in patients with CSU unresponsive to standard doses as the next step in treatment. A meta-analysis found that the rate of response in patients with CSU who responded to updosing was 63.2%. Therefore, approximately 40% of patients continue to have persistent hives and itching requiring treatment with the biologic omalizumab, based on evidence from randomized controlled trials. Although omalizumab has been shown to markedly relieve symptoms of CSU, omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. Thus, there is an unmet need for more effective treatments that can lead to cure or long-term remission. In this review, we will provide an overview of new treatment targets and biologics that are under investigation for the treatment of CSU.
TMC435 150 mg once daily (q.d.) for 10 days on Days 1 to 10, coadministered with a single 100-mg dose of cyclosporine on Day 7 and after a wash out period of at least 10 days, a single 100-mg dose of cyclosporine.
FIELD: medicinal biochemistry, medicine. SUBSTANCE: invention relates to medicinal agent comprising supersmall doses of monoclonal, polyclonal immune or natural antibodies in activated form raised to substance being mainly to protein or peptide taking part in carbohydrate or lipid metabolism or regulating indicated species of metabolism. Antibodies are prepared by method of multiple successive dilution and external effect being mainly by homeopathic technology. Invention relates also to method of regulation of carbohydrate and lipid metabolism by administration of indicated medicinal agent. Invention provides the development of effective preparation for regulation o carbohydrate and lipid metabolism and for prophylaxis and treatment of complications caused by impairment of carbohydrate and lipid metabolism and exhibiting specific pharmacological activity, absence of by-side effects, ecological purity and low cost. EFFECT: improved method of regulation, valuable properties of agent. 3 cl
After randomization, participants assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day were discharged. Treatment was provided by the researchers. Subjects were evaluated daily at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.
Children with hemiparesis, or weakness on one side of the body, caused by neurological conditions such as cerebral palsy or brain injury often experience difficulty using their arm and hand on their affected side (unilateral function), using both arms together (bimanual coordination) and participating in meaningful activities (occupational performance). Constraint Induced Movement Therapy (CIMT) has become one of the most evidence-based treatments for children with unilateral hemiplegia. Constraint Induced Movement Therapy involves constraining the non-affected arm and hand using a cast or sling to promote the use of the affected hand. Though CIMT offered on an individual basis to children in their own homes has been found to be effective, there are disadvantages to individual, signature models or caregiver delivered models of CIMT which include cost, decreased in number of children who can receive the therapy, and caregiver burden. Group based CIMT offers an alternative model of delivery for CIMT intervention that alleviates some of the challenges. The goal of this overall project was to evaluate the effectiveness of an intensive, group-based Constraint Induced Movement Therapy (CIMT) program for young children ages 20 months through 6 years of age with hemiparesis. The children attended a month-long intensive, group based CIMT program lasting 3 hours/day x 5 days/week x 4 weeks. For the first 3 weeks the children wore a cast on their non-affected arm for nearly 24 hours a day. During the last week of the program, the occupational therapists removed the cast and focused on bimanual skills (using both hands together). The children participated in testing that measured unilateral function (performance of the weaker arm such as range of motion, grasp, ability to bear weight or catch self), bimanual coordination (the ability to use both hands for functional tasks such as holding a toy, cutting food), and occupational performance (the ability to participate in meaningful daily activities- dressing, play, school-related activities). Study 1 analyzed the effects of a single dosage of the CIMT intervention (attending the program for one month). The investigators hypothesized (predicted) that following the study, the children would statistically significantly improve unimanual function, bimanual coordination, and occupational performance. Study 2 analyzed the effects of two, consecutive episodes of CIMT intervention (attending the CIMT program for 2 summers in a row). The researcher hypothesized children would display statistically significant improvements in unimanual function, bimanual coordination, and occupational performance after each episode.
This is a double-blind (neither the physician nor the patient knows the name of the assigned drug) study evaluating pain relief, safety, and tolerability of a new treatment (JNJ-42160443) for moderate to severe pain of osteoarthritis of the knee in comparison to a standard pain treatment and placebo. The study will last for about 42 weeks. Patients will receive treatment for 16 weeks. Patients who qualify for the study based on their level of pain as well as other factors will receive one of the 4 possible treatments as determined by chance. Before entering the study, patients must stop using their present pain medication. During the study, patients will answer questions about their pain, side effects, and have tests performed to monitor their physical condition. The main purpose of the study is to compare pain relief with JNJ-42160443 to that of a standard pain treatment or placebo. After the treatment period, patients can return to taking the pain medication that they used before the start of the study, and their physical condition will continue to be monitored. JNJ 42160443 10 mg/mL will be provided for use in the study. Patients will receive 1 of 4 treatments for 16 weeks (wks): lower dosage of JNJ 42160443 by subcutaneous (under the skin) (SC) injection once every 4 wks + Placebo (P) capsule orally (by mouth) (PO) 2x/day, higher dosage of JNJ 42160443 by SC injection once every 4 wks + P capsule PO 2x/day, standard pain medication capsule PO 2x/day + P by SC injection once every 4 wks, or P capsule PO 2x/day + P by SC injection once every 4 wks.