anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Systemic sclerosis (SSc) is a challenging autoimmune disease characterized by progressive fibrosis affecting the skin and internal organs. Despite the known infiltration of macrophages and neutrophils, their precise contributions to SSc pathogenesis remain elusive. In this study, we elucidated that CD206hiMHCIIlo M2-like macrophages constitute the predominant pathogenic immune cell population in the fibrotic skin of a bleomycin-induced SSc mouse model. These cells emerged as pivotal contributors to the profibrotic response by orchestrating the production of TGF-β1 through a MerTK signaling-dependent manner. Notably, we observed that neutrophil infiltration was a prerequisite for accumulation of M2-like macrophages. Strategies such as neutrophil depletion or inhibition of CXCR1/2 were proven effective in reducing M2-like macrophages, subsequently mitigating SSc progression. Detailed investigations revealed that in fibrotic skin, neutrophil-released neutrophil extracellular traps were responsible for the differentiation of M2-like macrophages. Our findings illuminate the significant involvement of the neutrophil-macrophage-fibrosis axis in SSc pathogenesis, offering critical information for the development of potential therapeutic strategies.
The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.
Participants will receive a single oral dose of fezolinetant in fed state on day 1 of study period 1. After a washout of 5 days the participants will receive a single oral dose of fezolinetant in fasted state on day 1 of study period 2.
Rheumatoid arthritis (RA) and arthrofibrosis (AF) are both chronic synovial hyperplasia diseases that result in joint stiffness and contractures. They shared similar symptoms and many common features in pathogenesis. Our study aims to perform a comprehensive analysis between RA and AF and identify novel drugs for clinical use. Based on the text mining approaches, we performed a correlation analysis of 12 common joint diseases including arthrofibrosis, gouty arthritis, infectious arthritis, juvenile idiopathic arthritis, osteoarthritis, post infectious arthropathies, post traumatic osteoarthritis, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, septic arthritis, and transient arthritis. 5 bulk sequencing datasets and 4 single-cell sequencing datasets of RA and AF were integrated and analyzed. A novel drug repositioning method was found for drug screening, and text mining approaches were used to verify the identified drugs. RA and AF performed the highest gene similarity (0.77) and functional ontology similarity (0.84) among all 12 joint diseases. We figured out that they share the same key pathogenic cell including CD34 + sublining fibroblasts (CD34-SLF) and DKK3 + sublining fibroblasts (DKK3-SLF). Potential therapeutic target database (PTTD) was established with the differential expressed genes (DEGs) of these key pathogenic cells. Based on the PTTD, 15 potential drugs for AF and 16 potential drugs for RA were identified. This work provides a new perspective on AF and RA study which enhances our understanding of their pathogenesis. It also shed light on their underlying mechanism and open new avenues for drug repositioning studies.
The present invention relates to a pure traditional Chinese medicine composition for curing child bedwetting and adult bedwetting. The pure traditional Chinese medicine composition is mainly prepared from the raw material medicine of the following part by weight: 1 to 3 parts of fructus lycii, 2 to 4 parts of dodder seed, 2 to 4 parts of astragalus root, 1 to 3 parts of palmleaf raspberry fruit, 1 to 2 parts of fructus, 1 to 2 parts of sharpleaf galangal fruit, 1 to 2 parts of herba cistanchis, 1 to 2 parts of common fennel fruit, 2 to 3 parts of mantis egg-case, 0.5 to 1.5 parts of polygala root, 2 to 4 parts of fructus cornt and 1 to 2 parts of eucommia bark. The medicine components of the present invention are all natural medicine materials. The pure traditional Chinese medicine composition of the present invention can warm and recuperate kidney yang, induce resuscitation and disenchant the brain, soothe the nerve and calm mind. The pure traditional Chinese medicine composition makes kidney qi vigorous and astringency proper, and the urinary bladder is gasified and inhibited. The pure traditional Chinese medicine composition has the effects of kidney replenishment, brain strengthening, urination reduction, intelligence benefiting, remembrance enhancement and promotion of teenager growth development, and has the obvious curative effect on symptoms, such as urgent micturition, frequent micturition, unending micturition, nocturia, spermatorrhea, weakness, anorexia, etc.
OBJECTIVE: Utilizing a novel histopathological scoring system and subglottic stenosis (SGS) rabbit model, we aimed to compare degrees of inflammation and severity of narrowing in the subglottis between two minimally invasive therapeutic modalities: endoscopic balloon dilation (EBD) alone versus EBD with placement of a bioabsorbable ultra-high ductility magnesium (UHD-Mg) alloy stent.
METHODS: SGS was induced endoscopically via microsuspension laryngoscopy in 23 New Zealand white rabbits. The control group (n = 11) underwent EBD alone, the study arm (n = 12) underwent EBD with implantation of bioabsorbable UHD-Mg alloy stents. Rabbits were euthanized at 2-, 3-, and 6-weeks after SGS induction, coinciding with wound healing stages. Using Optical Coherence Tomography (OCT), cross-sectional areas of airways were compared to calculate the mean percentage of intraluminal area at sequential time points. A novel histopathological scoring system was used to analyze frozen sections of laryngotracheal complexes. The degree of inflammation was quantified by scoring changes in inflammatory cell infiltration, epithelial ulceration/metaplasia, subepithelial edema/fibrosis, and capillary number/dilation. Univariate analysis was utilized to analyze these markers.
RESULTS: We found rabbits implanted with the bioabsorbable UHD-Mg alloy stent had statistically significantly higher scores in categories of hyperplastic change (stents vs controls: 1.48 vs 0.46 p < 0.001), squamous metaplasia (22 vs 5 p < 0.001), and neutrophils/fibrin in lumen (31 vs 8, p < 0.001). Rabbits who received EBD alone had higher scores of subepithelial edema and fibrosis (2.70 vs 3.49, p < 0.0256). The stented rabbits demonstrated significantly increased mean percent stenosis by intraluminal mean area compared to controls at 2 weeks (88.56 vs 58.98, p = 0.032), however at all other time points there was no significant difference between intraluminal subglottic stenosis by mean percent stenosis area.
DISCUSSION: Rabbits with SGS treated with UHD-Mg alloy stents demonstrated histopathologic findings suggestive of lower levels of tracheal fibrosis. This could indicate a reduced tendency towards the development of stenosis when compared to EBD alone. There was not a difference in luminal size between stent and non-stented rabbits at the six-week end point. Histologically, however, overall the use of bioabsorbable UHD-Mg alloy stenting elicited a greater tissue response at the level of the superficial mucosa rather than fibrosis of the lamina propria seen in the stented rabbits. This suggests more favorable healing and less of a tendency towards fibrosis and stenosis even though there may not be a benefit from a luminal size standpoint during this early healing period. Compared to known complications of currently available non-bioabsorbable metal or silicone-based stents, this proof-of-concept investigation highlights the potential use of a novel biodegradable UHD-Mg stent as a therapeutic modality for pediatric SGS.
After securing the IV, weight appropriate LMA will be inserted and sevoflurane continued at 3% inspired concentration. Oxygen in air will be delivered via LMA at 2 lpm. The sevoflurane may be increased or decreased in 0.5% increments as needed.
PROBLEM TO BE SOLVED: To obtain a lipid metabolism improver effective for preventing and bettering arteriosclerosis, comprising a fermented soybean milk prepared by treating a soybean milk with a bacterium belonging to the genus Bifidobacterium as a main component. SOLUTION: A soybean milk is optionally mixed with nutrients such as saccharides, e.g. sucrose or glucose, meat essence and peptone required for proliferation of bacterium, optionally adjusted to proper pH, inoculated with a bacterial liquid of a bacterium (e.g. Bifidobacterium breve) belonging to the genus Bifidobacterium and fermented by properly determining conditions such as temperature, time and anaerobic properties in the case of anaerobic bacterium suitable for the bacterium to give a fermented soybean. The fermented soybean milk is optionally mixed with a additives such as saccharides, protein, lipid and vitamin generally used in foods and oral medicines to given a lipid metabolism improver. The daily dose is 1000-500mL per adult.
The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients' quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking. The actual management of ITP is based on immune suppression (corticosteroids and intravenous immunoglobulins), or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors. A better understanding of the underlying pathology has facilitated the development of a number of new targeted therapies (Bruton's tyrosine kinase inhibitors, neonatal Fc receptors, strategies targeting B and plasma cells, strategies targeting T cells, complement inhibitors, and newer TPO-RAs for improving megakaryopoiesis), which seem to be highly effective and well tolerated and result in a significant improvement in patients' quality of life. The disadvantage is that there is a lack of knowledge of the predictive factors of response to treatments, which would help in the development of an optimized treatment algorithm for selected patients.
Enlarged vestibular aqueduct (EVA) is one of the most common forms of inner ear malformation that cause sensorineural hearing loss (SNHL). Some patients with EVA present delayed, fluctuating, and progressive hearing loss, while the others are with congenital or sudden hearing loss. Cochlear implants (CI) have been widely used in patients with severe-profound SNHL. However, it is difficult to define the optimal timing of CI operations for patients with EVA. Mutations in SLC26A4 are known to be responsible for EVA. This study is to explore the genotype-phenotype correlation of SLC26A4 mutations in cochlear-implanted patients with EVA.
Lenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Temsirolimus starting dose: 15 mg by vein every week for a 28 day cycle.
Senior high cost users (HCUs) with annual healthcare expenditures within the top 5% of Ontarians will be identified using established ICES costing algorithms. This cohort will be matched to a cohort of non-HCUs using a 3:1 matching ratio (non-HCU to HCU) based on age at cohort entry (+/- 1 month), sex and geographic location of residence (based on LHIN) for comparative analysis. Descriptive statistics will be used to describe the study populations and outcomes. Regression analyses will be used to adjust for potential confounders when analyzing healthcare resource utilization and costs as a function of HCU status (e.g. income, type of residence, co-morbidities, rural/urban) and/or when analyzing sub-populations \[e.g. chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF)\]. Logistic regression will be performed using the patient level data to predict the impact of individual factors on the likelihood of becoming a senior HCU.
The present disclosure relates to node deduplication based on a node merging policy. A plurality of node profiles may be maintained. Each node profile may include plurality of fields. Each field of the plurality of fields may include one or more values. For a node profile including one or more field-value pairs, each field-value pair may be identified. Each field-value pair may include a value of a field. A respective weight may be assigned to each field-value pair based on a number of field-value pairs or a confidence score. Based on the respective weights assigned to each field-value pair, it may be determined that node profiles satisfy a node profile merging policy. The node profiles may be merged based on the node profiles satisfying the node profile merging policy. Field-value pairs including a value of a field may be identified.
The invention relates to an isolated nucleic acid molecule that encodes a protein that is effective to preserve progenitor cells, such as hematopoietic progenitor cells. The nucleic acid comprises a sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof. The encoded protein has an amino acid sequence that comprises a sequence defined by SEQ ID NO:2, a homolog thereof, or a fragment thereof that contains an amino acid sequence TNNVLQVT. Methods of using the encoded protein for preserving progenitor cells in vitro, ex vivo, and in vivo are also described. The invention, therefore, includes methods such as myeloablation therapies for cancer treatment wherein myeloid reconstitution is facilitated by means of the specified protein. Other therapeutic utilities are also enabled through the invention, for example, expanding progenitor cell populations ex vivo to increase chances of engraftation, improving conditions for transporting and storing progenitor cells, and facilitating gene therapy to treat and cure a broad range of life-threatening hematologic diseases.
PROBLEM TO BE SOLVED: To obtain the subject microsphere readily formable a micro liquid drop and readily admirable by dispersing a chemical material in a melt of a waxy mixture, solid at a normal temperature, selected from a hardened oil and fat, a long chain higher aliphatic alcohol and a specific higher aliphatic multihydric alcohol partial ester, spraying the resultant dispersion by a centrifugal spraying method and cooking. SOLUTION: This microsphere is obtained by dispersing a chemical material, e.g. theophylline, ibuprofen or dextromethorphan in a melt of a waxy mixture in a state of a solid at a normal temperature, selected from (A) a hardened oil and fat (e.g. a hardened castor oil), (B) a long chain higher aliphatic alcohol (e.g. cetyl alcohol or stearyl alcohol) and (C) a higher aliphatic acid multihydric alcohol partial ester having <11 HLB (hydrophilic-lipophilic balance) (e.g. sorbitan monostearate) as a matrix base agent, spraying the resultant dispersion by a centrifugal spraying method and cooking. Preferably, 5-50 wt.% of the component A and 5-30 wt.% of the component C are respectively contained in the waxy mixture.
An interactive three-dimensional (3D) pointing device for selecting points within a subject employs a tracking device which determines the position of the operator, a semi-transparent screen positioned by the operator and the subject and provides this information to a model workstation. The model workstation superimposes computer graphic images of internal structures of the subject on a the semi-transparent screen through which the operator is viewing the subject. The superimposed image is derived from image data either previously generated and stored or obtained with an imaging system. The images of the internal structures are registered with the operator's view of the external structures of the operator. The operator interactively views internal and external structures and the relation between them simultaneously, while moving the screen to select 3D target points at an image depth within the subject. Optionally other input devices may be used to identify current `target points` as selected points. The 3D points are then provided to an output device which utilizes them. Another embodiment employs stereoscopic viewing methods to provide 3D representations of the internal images superimposed on external structures to allow the operator to employ parallax to select 3D points.
NEW MATERIAL:An amyloidal protein, derived from canine blood serum and capable of exhibiting average 13,700 molecular weight measured by a column gel filtration method and average 12,000 molecular weight measured by an SDS-polyacrylamide gel electrophoresis in the canine blood serum sensitized to Staphylcoccus aureus. USE:Reagents for detecting and determining amyloidal proteins derived from canine blood serum and diagnostic agents for canine diseases. PREPARATION:For example, Staphylococcus aureus is inoculated into the abdominal cavity of a dog and canine blood serum is collected after 2 days. KBr is then added to the collected canine blood serum to regulate specific gravity. Centrifugal separation is subsequently carried out at a high speed and the lower part of the supernatant is collected and dialyzed. The resultant dialyzate is treated with an ether, etc., defatted and washed. The obtained fraction is then subjected to repeated gel filtration to perform ion exchange chromatography and purified to afford the objective amyloidal protein derived from the canine blood serum.
This study explored the effects of a novel intervention, binaural beats (BB), on anxiety levels of anatomy students during cadaveric dissections and its impact on the learning environment. The study was quasi-experimental, employing a purposive sampling strategy. State (SA) and trait (TA) anxiety levels were measured using the State-Trait Anxiety Inventory during two routine dissection sessions. SA was measured at three time points: at the start, after a 3-min control (silence)/intervention (10 Hz BB) session, and at the end of the dissection. A post-study survey was distributed to the participants to obtain qualitative feedback on their perceptions of BB use during cadaveric dissections. Thirteen female students participated in this study (mean age 19.62 ± 0.65 years). Both control and intervention measures significantly reduced SA levels, with BB demonstrating a greater effect size (Hedges' g = 0.98 for intervention vs. 0.76 for control). SA decreased significantly after the BB intervention (t(12) = 3.78, p = 0.003) and remained low throughout the session, in contrast to the control session, where the reduction post-measure was not sustained (t(12) = -0.64, p = 0.54). Feedback from the post-study survey indicated that most students found the BB intervention effective in reducing their anxiety levels before the dissection. The BB intervention was effective in reducing and maintaining students' SA levels during dissection. Students reported positive experiences with BB. Further investigations are warranted to determine whether the findings of this study can be generalized to larger and more heterogeneous populations.
The present invention pertains to the fight against antibiotic resistances. Multidrug-resistant bacteria are a major public health concern. This situation is particularly critical among extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae. The inventors showed that nanoparticles comprising an antibiotic and an antisense oligonucleotide targeting a gene responsible for bacterial resistance to this antibiotic, bound through interactions with a nucleolipid compound, led to an increased anti-resistance activity, compared to non-vectorized oligonucleotides. In particular, the present invention relates to an oligonucleotide solid nucleolipid nanoparticle comprising: (i) an antibiotic molecule, (ii) a nucleolipid, and (iii) an antisense oligonucleotide targeting an mRNA encoding a protein responsible for bacterial resistance to the antibiotic recited in (i), wherein the antibiotic and the nucleolipid molecules form ion pair nanoparticle which is functionalized by the antisense oligonucleotide. Particularly, the inventors tested a novel nanoformulation consisting of a nucleolipid carrier DOTAU, ceftriaxone and an antisense oligonucleotide targeting CTX-M-15.
AIMS: Hypertension is associated with an increased activity of matrix metalloproteinase (MMP)-2 in the vasculature, which, in turn, proteolyzes extra- and intracellular proteins that lead to vascular dysfunction. The activity of sarcoplasmic reticulum calcium ATPase (SERCA) is decreased in the aortas of hypertensive rats. Increased activity of MMP-2 proteolyzed SERCA in rat heart during ischemia and reperfusion injury, thus impairing cardiac function. Therefore, we examined whether increased activity of MMP-2 in early hypertension contributes to proteolyze SERCA in the aortas, thus leading to maladaptive vascular remodeling and dysfunction.
MAIN METHODS: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with doxycycline. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. After 7 days, aortas were collected for zymography assays, Western blot to SERCA, ATPase activity assay, vascular reactivity, Ki-67 immunofluorescence and hematoxylin/eosin stain.
KEY FINDINGS: SBP was increased in 2K-1C rats and doxycycline did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and doxycycline decreased Ki-67. In 2K-1C rats, arterial relaxation to acetylcholine was impaired and doxycycline ameliorated it.
SIGNIFICANCE: doxycycline reduced MMP-2 activity in aortas of 2K-1C rats and prevented proteolysis of SERCA and its dysfunction, thus ameliorating hypertension-induced vascular dysfunction.