anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC0-∞, AUMC0-∞, t1/2, and MRT0-∞) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX.
The Cold Pressor Test (CPT) was introduced as a standard incentive for studying the vasomotor response (Hines and Brown 1932). Hyper-reactors were the subjects in his study who responded more strongly to CPT, Participants who show hyper reactivity to Cold pressor test (i.e. subjects showing 25 mmHg increase in systolic blood pressure along with 20 mmHg increase in diastolic blood pressure).They proposed that these hyper reactive could be candidates for hypertension in the future. Increased occurrence of these diseases could be attributed to an asymmetry in sympathetic and parasympathetic stimulation. Control or adaptation of breathing or breathing workouts i-e yoga are thought to be beneficial in the treatment of such disease. Although Yoga techniques proven to be effective in treating stress related disorders but it is time consuming and young population because of their busy routine couldn't be able to take out time for their health related issues. This study introduces very simple exercise in the form of left nostril breathing which decreases sympathetic activity and increases parasympathetic activity. It is inversely proportional to stress induced response of the body, it is very easy to perform and can be done at any time, and if found significantly effective for stress disorder ,it could be used in daily routine by our youth to get themselves prevented from major risk factors of CVD's particularly hypertension. This study will identify participants with a high potential risk of developing hypertension in the future by administering Cold pressor test, additionally the effects of left nostril breathing intervention on hyper reactive participants would be observed and if found significant, it would be a major breakthrough in primary prevention of hypertension.
BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms.
CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease.
CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.
COPD is a highly prevalent disease, with a prevalence among people 40 years of age or older of 10.1% worldwide and 13.7% in China. COPD has become the third leading cause of death worldwide. Frequent acute exacerbation and exercise limitation broadly exist in COPD patients, especially those in GOLD stage 3 or 4. Although appropriate pharmacological therapies have been proven to be effective in COPD management, however, many gaps are still to be filled. For example, the adverse effects of pharmacologic therapies can never be ignored. The investigator's previous studies suggested that traditional Chinese medicine (TCM) has effect on GOLD stage 3 or 4 COPD.

This is a multicenter, randomized, double-blind, placebo controlled trial to evaluate the effect of Bufei Yishen granule on reducing acute exacerbation in GOLD stage 3 or 4 COPD subjects. After a 14-day run-in period, 348 subjects will be randomly assigned to treatment group or control group for 52-week treatment. The primary outcomes are frequency and duration of acute exacerbation. The secondary outcomes include mortality, pulmonary function, clinical symptoms, exercise capacity, quality of life and treatment satisfaction. Safety will also be assessed.
Purpose: We aimed to investigate the association between the early mean arterial pressure (MAP)/norepinephrine equivalent dose (NEQ) index and mortality risk in patients with shock on vasopressors and further identify the breakpoint value of the MAP/NEQ index for high mortality risk. Methods: Based on the Medical Information Mart for Intensive Care IV database, we conducted a retrospective cohort study involving 19,539 eligible intensive care unit records assigned to three groups (first tertile, second tertile, and third tertile) by different MAP/NEQ indexes within 24 h of intensive care unit admission. The study outcomes were 7-, 14-, 21-, and 28-day mortality. A Cox model was used to examine the risk of mortality following different MAP/NEQ indexes. The receiving operating characteristic curve was used to evaluate the predictive ability of the MAP/NEQ index. The restricted cubic spline was applied to fit the flexible correlation between the MAP/NEQ index and risk of mortality, and segmented regression was further used to identify the breakpoint value of the MAP/NEQ index for high mortality risk. Results: Multivariate Cox analysis showed that a high MAP/NEQ index was independently associated with decreased mortality risks. The areas under the receiving operating characteristic curve of the MAP/NEQ index for different mortality outcomes were nearly 0.7. The MAP/NEQ index showed an L-shaped association with mortality outcomes or mortality risks. Exploration of the breakpoint value of the MAP/NEQ index suggested that a MAP/NEQ index less than 183 might be associated with a significantly increased mortality risk. Conclusions: An early low MAP/NEQ index was indicative of poor prognosis in patients with shock on vasopressors.
This is a double-blind, randomized, controlled, parallel group, outpatient clinical trial, involving a total of 270 patients diagnosed with dentin hypersensitivity, who will be randomly assigned to nine treatment groups of 30 patients each. Males or females of age 18 to 80 years will be enrolled. The nine groups will be randomly assigned to use one of the nine test products: (1) toothpaste containing nano-HAP (high concentration); (2) toothpaste containing nano-HAP (low concentration); (3) toothpaste containing nano-HAP and potassium nitrate (KNO3); (4) toothpaste containing NovaMin; (5) standard fluoride toothpaste with 1500 ppm MFP; (6) toothpaste containing nano-HAP (medium concentration); (7) placebo toothpaste; (8) cream containing nano-HAP; (9) placebo cream. Subjects will be instructed to use the study toothpaste as their sole oral hygiene product for the 8 weeks treatment duration while the cream will be applied with a retainer tray for 5 minutes before bed at night. For those using toothpastes, subjects will be instructed to brush their teeth twice daily for 2 minutes, morning and last thing before bed, applying on each occasion a one-inch strip of their assigned toothpaste on a wetted commercially available soft-bristled toothbrush. Dentin hypersensitivity examination, which will include air blast sensitivity and cold thermal sensitivity combined with visual analog scale and Dental Pain Scale, will be conducted at baseline, 2, 4, 6, and 8 weeks. Subjects will be screened for adverse effects on every visit, and all observed adverse events will be recorded when they occur.
The invention discloses a purely traditional Chinese agent and making method to prevent and treat chicken coccidiosis, which comprises the following parts: Chinese bulbul, dichroa febrifuga, sweet wormwood, hairy vein agrimony, feizi, areca seed, honeysuckle flower, astragalus root and so on. The making method comprises the following steps: weighing each drug material to add 1. 5 times water to soak; extracting 2h under 95 deg. c; filtering; condensing the filtrate under vacuum to form 1. 2 extract; adding 70% rice husk powder according to the weight of extract; drying. The invention doesn't produce drug tolerance without residuals and side effect to improve the utility of the fodder, which reduces the feeding cost of the chicken to improve the immunity of the chicken and disease resistance and growing speed.
The capillarization of hepatic sinusoids resulting from the activation of hepatic stellate cells poses a significant challenge, impeding the effective delivery of therapeutic agents to the Disse space for liver fibrosis treatment. Therefore, overcoming these barriers and achieving efficient drug delivery to activated hepatic stellate cells (aHSCs) are pressing challenge. In this study, we developed a synergistic sequential drug delivery approach utilizing neutrophil membrane hybrid liposome@atorvastatin/amlisentan (NCM@AtAm) and vitamin A-neutrophil membrane hybrid liposome @albumin (VNCM@Bai) nanoparticles (NPs) to breach the capillary barrier for targeted HSC cell delivery. Initially, NCM@AtAm NPs were successfully directed to the site of hepatic fibrosis through neutrophil-mediated inflammatory targeting, resulting in the normalization of liver sinusoidal endothelial cells (LSECs) and restoration of fenestrations under the combined influence of At and Am. Elevated tissue levels of the p-Akt protein and endothelial nitric oxide synthase (eNOS) indicated the normalization of LSECs following treatment with At and Am. Subsequently, VNCM@Bai NPs traversed the restored LSEC fenestrations to access the Disse space, facilitating the delivery of Bai into aHSCs under vitamin A guidance. Lastly, both in vitro and in vivo results demonstrated the efficacy of Bai in inhibiting HSC cell activation by modulating the PPAR γ/TGF-β1 and STAT1/Smad7 signaling pathways, thereby effectively treating liver fibrosis. Overall, our designed synergistic sequential delivery system effectively overcomes the barrier imposed by LSECs, offering a promising therapeutic strategy for liver fibrosis treatment in clinical settings.
The underlying pathology of atopic dermatitis (AD) consists of defective skin barrier function, susceptibility to Staphylococcus aureus skin infection, and immune imbalance. There is currently no cure for AD. Preclinical data in a mouse model of AD suggest that commensal Gram-negative bacteria (CGN), such as Roseomonas mucosa, from a healthy source can relieve symptoms of AD and have antimicrobial effects. In this study, we will first evaluate the safety of R mucosa-based biotherapy in adults with AD (age 18+ years; part 1), and then evaluate the safety and activity of R mucosa-based biotherapy in children (ages 3-17 years) with AD (parts 2A and 2B). In part 1, participants will receive twice-weekly doses of CGN biotherapy for 6 weeks, with dose escalations at 2 and 4 weeks. In part 2, participants will receive twice-weekly doses of CGN biotherapy for 4 months, with possible dose escalations at 4 and 8 weeks (part 2A only). Starting at 12 weeks for both parts 2A and 2B, dosing frequency may be increased to every other day. Participants in part 1 will be contacted 30 10 days after end of treatment for assessment of safety. Participants in parts 2A and 2B will also be followed for up to 1 year after the end of treatment for evaluation of long-term activity and safety. This will be the first study to test cutaneous live biotherapeutic products for AD. We hypothesize that altering the strains of CGN on the skin of people with AD will improve the patient s clinical outcome. We do not expect serious toxicities because R mucosa is rarely pathogenic; reported cases of bacteremia have typically been associated with percutaneous catheters in immunocompromised patients, who are excluded from this study.
The invention discloses a polypeptide for resisting rheumatoid arthritis. The amino acid sequence of the polypeptide is shown as SEQ ID NO.1-SEQ ID NO.9. The polypeptide is used to inject rats and then animal arthritis symptom is artificially induced. The result shows that the bodies of rats injected with the polypeptide generate corresponding antibodies, the concentration of vascular endothelial growth factors are simultaneously and correspondingly reduced and more than 90 percent of rats do not appear a rheumatoid arthritis symptom after being injected with II type collagen. The histopathology analysis shows that angiogenesis of arthropathies of experiment animals are obviously reduced and the VEGF level is reduced. The experiments show that the polypeptide can inhibit articular synovial membrane capillary proliferation of the rheumatoid arthritis in an immune intervention mode, block off the nutrition path and the T cell infiltration path of synovial membrane cell proliferation and inhibit tissue inflammation and tissue damage, thereby inhibiting the progress of the pathologic process of the rheumatoid arthritis and being developed into a medicament for resisting rheumatoid arthritis.
BACKGROUND: MVA-BN vaccine (Jynneos, Imvamune, Imvanex) was used widely in the 2022 mpox outbreak. This experience provides real-world evidence about the vaccine's safety, particularly regarding intradermal use.
METHODS: Bavarian Nordic's global safety database was searched for all adverse events following immunization (AEFIs) with MVA-BN. AEFI numbers were compared among administration routes. Selected events and administered doses were graphed over the mpox outbreak period.
RESULTS: A total of 9585 AEFIs have been reported. The rate of myocarditis or pericarditis was <1 per 100,000 doses administered. Eighty-nine cases of syncope, fainting, or loss of consciousness were reported. This number rose after the August 2022 US emergency use authorization for intradermal administration, as did the proportion of all syncope AEFIs reported following intradermal administration (78,7 %).
CONCLUSION: Real-world data from large-scale administration of MVA-BN has confirmed the vaccine's established safety profile when administered subcutaneously. Intradermal administration is likely associated with increased syncopal event frequency.
BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up.
METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression.
RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods.
CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.
BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT.
METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed.
FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study.
INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART.
FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation.
TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.