anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
CaMKIIalpha new subtype and gene sequence and application. The new isomer CaMKIIalpha3 of calcium/calmodulin-dependent protein kinase-II alpha (CaMKIIalpha) cloned from monkey's functional cortex. The total length of this isomer's cDNA Coding sequence is 1266bp, the protein with 421 gene coding, the molecular weight of which is 47519 Dalton, isoelectric point (pI) is 8.02. CaMKIIalpha has very important role in the research of neuroscience study and memory mechanism. It is recognized as a kind of 'memory factor'. The decrease of expression of CaMKIIalpha is related with the alzheimer's disease. The CaMKIIalpha3 is not discovered in the frontal cortex of rattus norvegicus and dog. As a new isomer of CaMKIIalpha subtype, it can participate in the advanced neuro-recognition of advanced mammal. As a medicine target related to the study and memory as well as alzheimer's disease, it can provide new study orientation for the gene treatment and medicine development.
The gut microbiome, a complex community of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining human health and influencing disease outcomes. Recent advancements in sequencing technologies have revealed the intricate relationship between gut microbiota and various health conditions. This review explores the impact of gut microbiome dysbiosis on immune function, chronic inflammation, and cancer progression. Dysbiosis, characterized by an imbalance in microbial populations, can lead to immune dysfunction, creating a pro-inflammatory environment conducive to tumorigenesis. Gut microbiome metabolites, such as short-chain fatty acids and bile acids, also play a significant role in modulating these processes. The interplay between these factors contributes to the development and progression of HNC. Furthermore, this review highlights the potential of therapeutic interventions targeting the gut microbiome, including probiotics, prebiotics, and dietary modifications, to restore microbial balance and mitigate cancer risk. Understanding the mechanisms by which the gut microbiome influences HNC can provide valuable insights into novel preventive and therapeutic strategies. Future research should focus on elucidating the specific microbial taxa and metabolites involved in HNC, as well as the impact of lifestyle factors such as diet, alcohol consumption, and oral hygiene on the gut microbiome. By leveraging the growing knowledge of the gut microbiome, it may be possible to develop personalized approaches to cancer prevention and treatment, ultimately improving patient outcomes.
This is a double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (study in which an inactive substance is given to one group of participants, while the study medication is given to another group), multicenter (study conducted at multiple sites), 2-arm (two groups), parallel-group (each group of participants will be treated at the same time), randomized-withdrawal (participants receiving study medication for a specified time will be later randomized to receive either study medication or placebo.) study, including an open-label (all people know the identity of the intervention) induction phase. Approximately 200 participants will participate in this study. This study will consist of an induction phase, a maintenance phase, and a follow-up phase. During the induction phase (lasting 6 weeks) participants will receive 200 mg subcutaneous (SC) (under the skin) golimumab at Week 0 and 100 mg SC golimumab at Week 2. During the maintenance phase (up to Week 52) all participants who show a clinical response (measure of therapeutic effect of study medication) to golimumab during the induction phase will be randomly allocated in a 1:1 ratio to receive either SC administration of placebo (Group 1) or 100 mg golimumab (Group 2) every 4 weeks from Week 0 to Week 52. Participants who do not show clinical response to golimumab will also receive 100 mg SC administration of golimumab until Week 4 and if, by Week 8 of the maintenance phase, these participant's disease activity does not appear to be improving, participants will be discontinued from further study medication administration and will be followed up for safety evaluations 16 weeks after the last administration of study medication. However, if disease activity of these participants improves at Week 8, they will continue to receive golimumab (100 mg every 4 weeks) through Week 52 of the maintenance phase. The follow-up phase will be of 16 weeks duration. During this study, any participant who have a clinical response during the induction phase but lose clinical response at any time will be eligible for dose adjustment only once as follows: 1) participants receiving placebo (Group 1) will receive golimumab 100 mg; 2) participants receiving golimumab 100 mg (Group 2) will continue to receive golimumab 100 mg. Safety evaluations will include assessment of adverse events, laboratory measurements, antinuclear antibodies/anti-double-stranded deoxyribonucleic acid antibodies, and vital signs. The maximum study duration for a participant will be 68 weeks.
Heavy menstrual bleeding (HMB) is common among adolescents and young adults with an inherited bleeding disorder (BD) and negatively impacts health-related quality of life and physical and mental health status. Effective treatment options are available that decrease bleeding and improve quality of life, but were not studied in those with BD, so we do not know if there is similar effectiveness in this condition. We also do not know the impact of treatment on diagnostic testing for BD or on improvement of iron deficiency. Given these gaps in knowledge, the primary objective of the Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study is to conduct a multicenter prospective observational cohort study and registry, enrolling adolescents and young adults with heavy menstrual bleeding cared for at collaborating interdisciplinary menstrual clinic sites nationally who are choosing to start use of either of two commonly used progestin menstrual treatment options: levonorgestrel-releasing intrauterine system (LNG-IUD) or oral norethindrone acetate 5 mg daily (NETA) (N=300). In Aim 1, we will compare outcomes related to (a) bleeding management, (b) quality of life, and (c) repletion of iron storage levels after six months of treatment with either option in those with a diagnosed inherited bleeding disorder. The primary outcome will be treatment success with a Pictorial Blood Loss Assessment Chart (PBAC) score \<50 points by six months. Secondary objectives to assess bleeding management will include need for adjuvant management, change in PBAC from baseline to 6 months, and self-reported treatment success. Quality of life outcomes will include change in validated scales to assess health-related quality of life which are specific to adolescents and young adults in the setting of heavy menstrual bleeding. We will compare ferritin levels at six months compared to baseline to determine the relative amount of benefit obtained from either treatment option. In Aim 2, we will compare outcomes after LNG-IUD in those with and without a bleeding disorder, assessing rates of expulsion and method continuation between the two groups in addition to the outcomes assessed for Aim 1. In Aim 3, we will improve our understanding of the impact of physiological stress on BD diagnostic studies by comparing change in hemostatic parameters before and after successful treatment in those with HMB without a previously diagnosed bleeding disorder. This study will demonstrate the relative benefits of menstrual suppression treatment options for adolescents and young adults with heavy menstrual bleeding and inherited bleeding disorders, will provide population-specific estimates for expected benefit that can be used in treatment counseling, and will highlight the impact of treatment status on diagnostic test results.
This invention relates to antimicrobial wound dressings having a non-leaching antimicrobial activity, releasable antimicrobial and antiprotease agents, and a controlled-release bioactive agent such as doxycycline. The Wound dressing material is absorbent and acts as a substrate for antimicrobial and antiprotease agents as well as bioactive agents. More generally, this invention relates to methods and compositions for materials having a non-leaching coating that has antimicrobial properties. The coating is applied to substrates such as gauze-type wound dressings, powders and other substrates. Covalent, non-leaching, non-hydrolyzable bonds are formed between the substrate and the polymer molecules that form the coating. A high concentration of anti-microbial groups on multi-length polymeric molecules and relatively long average chain lengths, contribute to an absorbent or superabsorbent surface with a high level antimicrobial efficacy. Utilization of non-leaching coatings having a plurality of anionic or cationic sites is used according to this invention to bind a plurality of oppositely charged biologically or chemically active compounds, and to release the bound oppositely charged biologically or chemically active compounds from said substrate over a period of time to achieve desired objectives as diverse as improved wound healing to reduction in body odor.
PURPOSE:To provide a medicine for improvement of airway obstruction, containing a human polymorphonuclear leukocyte elastase inhibitory protein (SLPI) as the active component. CONSTITUTION:This madicine contains a polypeptide [e.g. (Arg<58>-Ala<107>)SLPI] having an amino acid sequence represented by the table, another polypeptide having the amino acid sequence or another polypeptide having an amino acid sequence biologically equal thereto as the active component. Preparation is possible in the form of an oral administration type and a parenteral administration type such as an intravenous injection type, a subcutaneous type, an intramuscular type, a dermal type, an aspiration type or an intrarectal type. The dosage of the polypeptide is 1 to 1000mg/time and administration is one to three times a day. This medicine is effective for, e.g. airway obstruction accompanying a respiratory disease in which the number of leukocytes in sputum or a bronchovesicule-wash liquid is increased, acute or chronic obstructive diseases caused by a neutrophil-or acidphil-derived protease or acute or chronic obstructive lung diseases caused by airway hypersensitive sthenia.
The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents that results in their localized production within the target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. Inactivation is also accomplished by engineering protease degradation sites within the therapeutic construct for proteases, preferably those that are under-expressed within the target tissue yet present in non-target tissues within the body, resulting in therapeutic activity within the target tissue and inactivation outside of the target tissue. Novel chimeric proteins secreted by bacteria are also described. The chimeric proteins include chimeric toxins targeted to neoplastic cells and cells of the immune system. Novel combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described. Non-conjugative bacteria capable of delivering phage/phagemids expression cassettes for DNA and RNA-based therapeutics are also described.
BACKGROUND: Predicting posthepatectomy liver failure (PHLF) may be a critical requirement for liver disease patients undergoing hepatectomy. This study retrospectively analyzed the impact of the intraoperatively measured portal vein pressure (PVP) prior to hepatectomy on the prediction of PHLF in hepatectomized patients.
METHODS: A total of 334 hepatectomized patients in whom the PVP was intraoperatively measured before resection at our institution were enrolled in the present study. Outcomes were assessed according to the International Study Group of Liver Surgery definition and the severity of PHLF grading.
RESULTS: Thirty-nine of the 334 patients (11.6%) developed grade B/C PHLF. The following factors were significantly associated with grade B/C PHLF in a univariate analysis: indocyanine green retention rate after 15 min, Child-Pugh score, prehepatectomy PVP, and transfusion (each P < 0.0001). A prehepatectomy PVP value of 19.5 cmH2O was the optimal cutoff value for predicting grade B/C PHLF. In a multivariate analysis, prehepatectomy PVP (≥ 19.5 cmH2O) was selected as the most relevant risk factor for grade B/C PHLF (P = 0.0003, hazard ratio: 5.96, 95% CI: 1.80-19.70).
CONCLUSIONS: Prehepatectomy PVP can serve as a useful predictor of the risk of PHLF in patients who have undergone hepatectomy. The results emphasize the possibility of reducing the planned extent of hepatic resection when the prehepatectomy PVP value measured intraoperatively exceeds 19.5 cmH2O, and the importance of predicting the PVP before the operation.
Part I - 100 milligram (mg) BI 730357 taken orally once daily as a film-coated tablet in the morning while fasted for 12 weeks in period 1 followed by the same treatment for 12 weeks in period 2 (total treatment period of 24 weeks). Participants who failed to achieve a Psoriasis Area Severity Index score (PASI) 50 response at Week 12 were switched to a 200 mg dose, participants switching dose were imputed as failure for records after week 12, under original randomized treatment arm.
Phase II Anaplastic Glioma (AG) participants received the regimen established in the Phase I study (Feb 2011). Phase II participants received bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle and LBH589 30 mg/day orally, 3x per week, every other week (Days 1, 3, 5, 15, 17, 19). Participants were treated until disease progression or unacceptable toxicity.
A mechanistic, dynamic model was developed to calculate body composition in growing lambs by calculating heat production (HP) internally from energy transactions within the body. The model has a fat pool (f) and three protein pools: visceral (v), nonvisceral (m), and wool (w). Heat production is calculated as the sum of fasting heat production, heat of product formation (HrE), and heat associated with feeding (HAF). Fasting heat production is represented as a function of visceral and nonvisceral protein mass. Heat associated with feeding (HAF) is calculated as ((1 - km) x MEI), where km is partial efficiency of ME use for maintenance, and MEI = metabolizable energy intake) applies at all levels above and below maintenance. The value of km derived from data where lambs were fed above maintenance was 0.7. Protein change (dp/dt) is the sum of change in the m, v, and w pools, and change in fat is equal to net energy available for gain minus dp/dt. Heat associated with a change in body composition (HrE) is calculated from the change in protein and fat with estimated partial efficiencies of energy use of 0.4 and 0.7 for protein and fat, respectively. The model allows for individuals to gain protein while losing fat or vice versa. When evaluated with independent data, the model performed better than the current Australian feeding standards (Freer et al., 2007) for predicting protein gain in the empty body but did not perform as well as for gain of fat and fleece-free empty body weight. Models performed similarly for predicting clean wool growth. By explicit representation of the major energy using processes in the body, and through simplification of the way body composition is computed in growing animals, the model is more transparent than current feeding systems while achieving similar performance. An advantage of this approach is that the model has the potential for wider applicability across different growth trajectories and can explicitly account for the effects of systematic changes on energy transactions, such as the effects of selective breeding, growth manipulation, or environmental changes.
Corticosteroids are currently the mainstay of therapy for active pulmonary sarcoidosis and are used to prevent relapses in many patients with stable disease. The pulmonary manifestations of sarcoidosis are heterogenous and not all patients require corticosteroid therapy. Corticosteroids often produce undesirable side effects and, therefore, other therapies that can reduce or replace corticosteroid use are being sought. As tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the formation of granulomata (the pathological hallmark of the disease), drugs that inhibit its production/release may prove effective in the treatment of this disease. Pentoxifylline (POF), a xanthine derivative used for many years in the treatment of peripheral vascular disease, is known to inhibit TNF-alpha release by human peripheral blood mononuclear cells and alveolar macrophages from patients with active sarcoidosis. To evaluate whether this drug is beneficial in the treatment of sarcoidosis, we propose to conduct a randomized, double-blind, placebo-controlled trial with POF in patients with pulmonary sarcoidosis on corticosteroid therapy. The primary objective of this study is to determine whether POF treatment can be beneficial as an adjunct to corticosteroid therapy in patients with pulmonary sarcoidosis. The role of TNF-alpha and other cytokines (released from alveolar macrophages) in explaining treatment responses defined by whether or not a patient improved will be assessed by testing whether the effect of treatment on the probability of improvement varies with cytokine levels.
<P>PROBLEM TO BE SOLVED: To provide complexes or fusions between two or more different cytokines.  <P>SOLUTION: There are provided protein complexes and fusion proteins including at least two different cytokine molecules. The protein complexes and fusion proteins may further include a targeting moiety such as a region of an immunoglobulin. Methods of using the protein complexes and fusion proteins are also disclosed. The protein complexes and fusion proteins including at least two different cytokines molecules are provided, which are generally useful in a similar way to the targeting immunotherapy. These protein complexes and fusion proteins include other protein functional groups if necessary. Such protein complexes and fusion proteins provide the activity of the component of cytokines in a fixed ratio.  <P>COPYRIGHT: (C)2011,JPO&INPIT
OBJECTIVE: Self-report instruments are commonly used in tinnitus clinics, but they are presently available only for adults. There is a lack of a validated multi-item instrument to capture tinnitus-related problems in children and their impact on everyday life. This study has developed and validated a specifically child-centered questionnaire to assess the impact of tinnitus.
METHODS: Development of the tool consisted of several stages. Following a pilot study on 12 children with tinnitus, a validation study was done on a further 192 children with tinnitus aged between 11 and 14 years. The children had an audiological examination, completed a Visual Analogue Scale (VAS) and the newly framed questionnaire.
RESULTS: The development and validation process resulted in the new 11-item Children's Tinnitus Questionnaire (CTQ). It includes items concerning the impact of tinnitus on functional, cognitive, emotional and social domains. The validity of the new tool has been established by finding significant correlations between it and VAS loudness (r = 0.42), VAS annoyance (r = 0.67), and VAS coping (r = -0.41). Validity has also been confirmed by measuring differences in CTQ scores and 4 groups of children having graded incidences of tinnitus. The internal consistency assessed with Cronbach's alpha was high (α = 0.82).
CONCLUSION: The Children's Tinnitus Questionnaire (CTQ) is the first fully validated multi-item instrument designed specifically for children. The tool has the potential to become a valuable new instrument for use in clinical practice and research; it might be useful for assessing the impact of tinnitus on those children who find that the condition creates problems in their everyday life.
Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities. Based in the Multi-Ethnic Study of Atherosclerosis, a longitudinal cohort study of community-dwelling adults, a comprehensive sleep study and an MRI of the upper airway and brain were performed on 578 participants. Machine learning models were used to select from 74 upper airway measures those measures most associated with selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between the selected upper airway measures, sleep measures, and brain structure. Maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and gray matter volume. Both coefficients were small (coefficients per standard deviation 0.063 mL, p = 0.04, and - 7.0 mL, p < 0.001 respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume (coefficient 0.164 mL, p = 0.007), and higher percentage of time in the N3 sleep stage was associated with larger total white and gray matter volume (4.8 mL, p = 0.004). Despite associations of two upper airway anatomy measures with brain volume, the evidence did not suggest that these upper airway and brain structure associations were acting primarily through the pathway of sleep disturbance.
BACKGROUND: Angiogenesis has been discovered to be a critical factor in developing tumors and ischemic diseases. However, the role of angiogenesis-related genes (ARGs) in acute myocardial infarction (AMI) remains unclear.
METHODS: The GSE66360 dataset was used as the training cohort, and the GSE48060 dataset was used as the external validation cohort. The random forest (RF) algorithm was used to identify the signature genes. Consensus clustering analysis was used to identify robust molecular clusters associated with angiogenesis. The ssGSEA was used to analyze the correlation between ARGs and immune cell infiltration. In addition, we constructed miRNA-gene, transcription factor network, and targeted drug network of signature genes. RT-qPCR was used to verify the expression levels of signature genes.
RESULTS: Seven signature ARGs were identified based on the RF algorithm. Receiver operating characteristic curves confirmed the classification accuracy of the risk predictive model based on signature ARGs (area under the curve [AUC] = 0.9596 in the training cohort and AUC = 0.7773 in the external validation cohort). Subsequently, the ARG clusters were identified by consensus clustering. Cluster B had a more generalized high expression of ARGs and was significantly associated with immune infiltration. The miRNA and transcription factor network provided new ideas for finding potential upstream targets and biomarkers. Finally, the results of RT-qPCR were consistent with the bioinformatics analysis, further validating our results.
CONCLUSIONS: Angiogenesis is closely related to AMI, and characterizing the angiogenic features of patients with AMI can help to risk-stratify patients and provide personalized treatment.