anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Placebo for ixekizumab administered by two SC injections at Week 0, then one SC injection per Dosing Regimen 1 until Week 12. Placebo for etanercept administered by one SC injection twice weekly starting at Week 0 up to Week 12. At Week 12, participants are assigned to Dosing Regimen 2.
With the approval of the first two substances for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), a standardized monitoring of patients treated with complement inhibitors in clinical practice is needed. Optical coherence tomography (OCT) provides high-resolution access to the retinal pigment epithelium (RPE) and neurosensory layers, such as the ellipsoid zone (EZ), which further enhances the understanding of disease progression and therapeutic effects in GA compared to conventional fundus autofluorescence (FAF). In addition, artificial intelligence-based methodology allows the identification and quantification of GA-related pathology on OCT in an objective and standardized manner. The purpose of this study was to comprehensively evaluate automated OCT monitoring for GA compared to reading center-based manual FAF measurements in the largest successful phase 3 clinical trial data of complement inhibitor therapy to date. Automated OCT analysis of RPE loss showed a high and consistent correlation to manual GA measurements on conventional FAF. EZ loss on OCT was generally larger than areas of RPE loss, supporting the hypothesis that EZ loss exceeds underlying RPE loss as a fundamental pathophysiology in GA progression. Automated OCT analysis is well suited to monitor disease progression in GA patients treated in clinical practice and clinical trials.
Early allograft dysfunction (EAD) is a frequent phenomenon, leading to increased graft loss and higher mortality after liver transplantation (LT). Despite significant efforts for early diagnosis of EAD, there is no existing approach that can predict EAD on the first post-operative day. The aim is to define a metabolite-based biomarker on the first day after LT complicated with EAD. Ten patients diagnosed with EAD and 26 non-EAD are recruited for the study. A HPLC-MS/MS is used to determine 14 amino acids and 15 bile acids serum concentration. Comparative analyses are conducted between EAD and non-EAD groups. Arginine is identified as the most significant metabolite distinguishing the EAD and non-EAD groups, and therefore, is identified as a potential biomarker of EAD. The optimal cut-off value for arginine is 52.09 µmol L-1, with an AUROC of 0.804 (95% confidence interval: 0.638-0.917, p < 0.001), yielding a sensitivity of 100%, specificity of 53.8%, and Youden index of 0.54, NPVof 100%, and PPV of 45.45%. In summary, the study indicated that targeted metabolomics analysis would be a promising strategy for discovering novel biomarkers to predict EAD. The identified arginine may be helpful in developing an objective diagnostic method for EAD.
Atopic dermatitis results in diminished barrier function and altered production of antimicrobial peptides. Dendritic epidermal T cells (DETCs) play an important role in the wound repair and inflammation process. Our previous work identified an IL-4-dependent loss of DETCs in Stat6VT mice and in the MC903-induced skin inflammation mouse model. However, the mechanisms through which IL-4 mediates the loss of DETCs are unclear. In this study, we show that IL-4Rα germline knockout mice (Il4ra-/-) have increased DETCs, faster wound healing, and increased epidermal differentiation complex gene and fibronectin expression. The absence of IL-4Rα minimized the MC903-induced loss of DETCs, and reciprocal bone marrow chimera experiments in Il4ra-/- and wild-type mice demonstrated structural nonhematopoietic IL-4-responsive cell-mediated DETC homeostasis. Skin keratinocyte-derived IL-15 decreased dramatically in the MC903 model, while injection of IL-15 rescued DETC loss by promoting DETC proliferation and limiting apoptosis. Conditional deletion of IL-4Rα from keratinocytes using Il4rafl/fl K14-Cre mice showed an increase of DETCs, increased IL-15 production, and diminished skin inflammation following wounding. These results suggest that IL-4-dependent effects on DETCs in allergic skin inflammation are mediated by the IL-4Rα receptor of keratinocytes.
PURPOSE:To provide a human monoclonal antibody reactive on carcinoembryonic antigen(CEA), useful for diagnosis and therapy of cancer and low in antigenicity against human. CONSTITUTION:A human monoclonal antibody specifically recognizes the sugar chain part in CEA. In this antibody, the immunoglobulin class belongs to IgG1 and the light chain is K chain. This human monoclonal antibody can be obtained by establishing anti-CEA antibody-producing human lymphocyte and culturing it. The established lymphocyte can be obtained by infecting the lymphocyte with EB virus so as to establish it, by fusing another established cell strain to the lymphocyte to form a hybridoma or by combining these two methods. The hybridoma capable of producing the human monoclonal antibody is preferably hybridoma strain BSRF-S-97 (FERM P-13920). This antibody can be applied, e.g. to an imaging agent for examining the position of a tumor of a cancer patient or a missile therapy for curing cancer by using it bonded to an antitumor substance.
Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.
This invention is directed to a compound having the formula (I), wherein N may be a nucleotide, n is from 1-5 and n' is from 1-3. Such asymmetric ribozymes have higher than normal cleavage rates. The compound may be covalently linked to a delivery agent. The invention also includes a composition which comprises the compound in association with an acceptable carrier. The invention also includes a method of cleaving an RNA target sequence with the compound as described above. Further, a method of treating a disease in man or animals associated with a particular RNA which comprises administrating to the man or animal the compound. Further, the invention also includes a diagnostic reagent which comprises the compound.
Participants will be randomly assigned to one of two groups. One group of breast cancer survivors will receive general information on how to adopt healthy lifestyle behaviors. The other group of breast cancer survivors will receive counseling on how to increase their level of physical activity.

Participants will have three consultations with a health counselor. The first two consultations will take place in-person and the third consultation will take place via telephone. Participants will also be asked to complete questionnaires assessing their physical and mental well-being, their dietary habits, and their physical activity habits at four time-points: in-person during their first study visit, via mail or through an online survey 6 weeks later, in-person 12 weeks later, and via mail or through an online survey 24 weeks later. Additionally, during their first study visit and 12 weeks later, their level of aerobic fitness will be tested by having participants walk a long hallway for six minutes.
BACKGROUND: Magnetic resonance elastography (MRE) is recognized as the most precise imaging technology for assessing liver fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the clinical factors and pathological characteristics that may impact LSM in MASLD patients.
METHODS: This cross-sectional study recruited 124 patients who concurrently performed MRE, MRI-PDFF, and biopsy-proven MASLD. Linear regression models, Spearman's correlation, and subgroup analysis were employed to identify the variables affecting LSM.
RESULTS: The AUROC (95 % CI) of MRE for diagnosing fibrosis stage ≥ 1, 2, 3, and 4 was 0.80 (0.70-0.90), 0.76 (0.66-0.85), 0.92 (0.86-0.99), and 0.99 (0.99-1.00), with corresponding cutoffs of 2.56, 2.88, 3.35, and 4.76 kPa, respectively. Multivariate analyses revealed that AST was the only independent clinical variable significantly correlated with LSM. Furthermore, LSM exhibited a notable association with the grade of lobular inflammation and hepatocellular ballooning. Subgroup analysis showed that when AST ≥ 2 ULN or inflammation grade ≥ 2, LSM of patients with early fibrosis stages showed a slight but significant increase.
CONCLUSION: MRE demonstrates significant diagnostic accuracy in predicting liver fibrosis stages for MASLD patients, especially for advanced liver fibrosis and cirrhosis. However, elevated AST and the severity of liver inflammation may impact its accuracy in staging early liver fibrosis.
PROBLEM TO BE SOLVED: To obtain a carcinostatic agent, capable of manifesting carcinostatic properties and hardly causing adverse effects on human bodies by using a specific crystalline compound belonging to the space group R3c. SOLUTION: This carcinostatic agent comprises a compound represented by the formula  A is an alkali metallic ion, an alkaline earth metallic ion, ammonium ion or H ion; M is a tetravalent metal; (n) is 0<=(n)<=61 (a) and (b) are each a positive number satisfying [(a)+(mb)]=1 [(m) is the valence of A]}, e.g. zirconium phosphate supporting silver. The compound is preferably baked at, e.g. 500-1,300 deg.C and the daily dose thereof for humans is preferably about 0.1-500 mg/kg. The carcinostatic agent is made present in a peripheral part of a lesion and irradiated with visible radiation at <=600 nm wavelength.
PURPOSE:To produce M4854-II, a substance to inhibit well beta-lactamase action, by cultivating a specific microorganism belonging to the genus Chaetomella, extracting, separating and purifying the culture mixture. CONSTITUTION:Fungus strain 4854 producing an inhibitory substance on beta- lactamse having beta-lactam structure cleavage action produced by a fungus resistant to penicillin, etc. by separating and searching a microorganism. Spore suspension of this microorganism or culture solution is inoculated into a production medium having a composition consisting of glucose, polypeptide, corn starch liquor, KH2PO4, etc., subjected to submerged aerated spinner at 24-28 deg.C for about 48-72hr, and M4854-II is produced in the culture solution. Then, the culture solution is filtered, treated with active carbon, or a resin, M4854-II is adsorbed, eluted with acetone, etc., to give a crude substance. The crude substance is purified by gel filtration, or column chromatography, and its active fraction is dried under reduced pressure to give M4854-II.
FIELD: medicine, pharmaceutical technology, pharmacy. SUBSTANCE: invention relates to method of preparing injection form of the preparation chondroitin sulfate used for treatment of arthrological and rheumatic diseases. Method involves separate preparing chondroitin sulfate solutions in sterile water, benzyl alcohol and sodium hydroxide followed by addition of sterilized solutions of sodium hydroxide (up to pH 6.2-6.8) and benzyl alcohol to chondroitin sulfate sterilized solution. Invention provides the development of a novel method of preparing the preparation preventing formation of derivatives of chondroitin sulfate and the preparation coloring. EFFECT: improved method of preparing. 1 ex
Parkinson's disease (PD) is a progressive neurodegenerative disease of central nervous system that mainly affects the motor system . The worldwide data showed a rising prevalence of PD with age. Meta-analysis showed a prevalence of 41/100,000 in 40-49 years old; 107/100,000 in 50-59 years; 173/100,000 in 55-64 years; 428/10,000 in 60-69 years; 425/10,000 in 65-74 years; 1087/10,000 in 70-79 years; and 1903/100,000 in \>80 years. Some differences in prevalence have been observed in different geographic location and in relation to sex . Patients with PD have multiple non-motor symptoms (NMSs) including fatigue, sensory symptoms, autonomic disturbance. sleep disorders, neuropsychiatric abnormalities etc . In the last decade and even in early stages of PD, studies reported hearing and/or vestibular dysfunctions in patients with PD with an estimated frequency of 25-50% . In the last decade and even in early stages of PD, studies reported vestibular dysfunctions in patients with PD with an estimated frequency of 14-25% compared to 5 -7.4% of the general population matched for age.

The pathophysiologic mechanisms of NMSs with PD are complex. Experimental as well as functional neuroimaging (e.g. SPECT and functional MRI) studies found that outputs from basal ganglia are directed to the inferior colliculus, medial geniculate nucleus, and temporal cortex. Motor or NMSs, occur due to loss not only of dopaminergic neurons in the substantia nigra but also in other dopaminergic and non-dopaminergic areas of the brain including serotoninergic, noradrenergic, and cholinergic systems. Lewy bodies and neurites consisting of α-synuclein, the main pathological features of PD, were observed in brain hemispheres as well as, spinal cord, brainstem nuclei and fiber tracts including vestibular nuclei and efferent neuronal system within the inner ear .

Diagnostic basic audiologic and vestibular evaluation and electrophysiological testing as brainstem auditory evoked potential (BAEP), videonystagmography (VNG) and cervical (cVEMP) and ocular (oVEMP) vestibular evoked myogenic potentials are easily available and applicable in many parts of the world as diagnostic tests to objectively evaluate peripheral and central auditory and vestibular dysfunctions for many disease including PD . This may provide early drug intervention and rehabilitation for patients and improve their qualities of life.
Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed to investigate this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age, 63 years). The overall response rate was 90% in response-evaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, high-risk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2-3 months prior to start of KRd treatment significantly decreased PFS and OS in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e., delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AE) were observed in 56% of the patients, and non-fatal or fatal AE that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large, real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.
One or more test devices (NTM, Bempu, Thermospot) will be attached to the infant in the neonatal intensive care unit (NICU) or KMC ward along with the Philips Intellivue patient monitor. Temperature will be monitored continuously using each device for up to 72 hours.
The present invention discloses an external targeted transdermal alkalescent blood adjusting agent and a preparing method thereof, which belongs to a medicine preparation which is characterized by sheet-shaped base material. The blood adjusting agent is prepared by the raw materials of onion extract, folium ginkgo extract, sudroma, wheat germ extract, hexosamine, zinc citrate dehydrate, calcium acetate, lycopin, etc. through the steps of extracting by alcohol, filtering, distilling, condensing, spray drying, and grinding the gel to paste after adding transdermal promoter and medical pressure-sensitive adhesive. The blood adjusting agent can be respectively prepared to patch, membrane agent or gelling agent according to the requirement of dosage form. According to the invention, the medicine is transdermal and enters the blood circulation directly. The blood acid can be quickly and effectively neutralized for remarkably reducing the blood acid. The tedious metabolism routing of oral medicine in vivo is prevented. The transdermal absorption causes that Ca, Zn and other alikaline matter directly and quickly enter to the blood stream for regulating the acid-alkali degree of blood.
Sudden infant death syndrome (SIDS) "gray zone" or borderline cases are those in which it is challenging to define whether the pathological findings are sufficiently severe to lead to death. We report a case of a 17-day old male newborn who came to our attention for unexplained death. A complete autopsy was performed, including close examination of the cardiac conduction system. Lungs presented diffuse alveolar damage and interstitial inflammation, the cardiac conduction system showed fetal dispersion, resorptive degeneration, junctional tissue islands and cartilaginous hypermetaplasia of the central fibrous body. The final cause of death was a "gray zone" SIDS. This case report will highlight the intersection of SIDS and pneumonia in newborns, exploring the challenges and controversies surrounding the diagnosis and management of this complex condition.
The present invention relates to a calcification hyperplasia paste and a preparation method thereof. The calcification hyperplasia paste belongs to an external application paste of pure traditional Chinese medicine, is used for treating hyperostosis, ankylosing spondylitis, cervical spondylosis and vertebral variation, and is composed of herba speranskiae tuberculatae, clematis root, magnolia officinalis, ledebouriella root, angelica dahurica, chiese eaglewood wood, angelica, frankincense, myrrh, prepared common monkshood daughter root, cassia bark, dragon blood, safflower, pangolin scale, eucommia bark, cassia twig, common floweringqince fruit, twotoothed achyranthes root, radix glycyrrhiza, musk, akira dan and sesame oil. The medicinal ingredients in a prescription are rendered by the sesame oil until the soil drip can become beads. The rendering liquid is deslagged and is put into the akira dan for forming the paste. The dosage of each plaster of the paste is 9.4g. The effective period of the medicine force is from 20 to 30 days. The symptoms can basically disappear when patients continuously take medicine for 4 to 5 months. The patients are forbided to eat hot pepper during the period of medicine taking. The patients who are allergic to alcohol are forbided to drink liquor. Besides, pregnant women do not allow pasting the paste.
Participants randomized to the TAU condition, which involves the standard clinical services available in a short term residential SUD treatment context. Examples of these services are: Individual counseling/case management; Group psychoeducation; Group counseling; Assessment and addiction related medical treatment from a physician; Pharmacotherapy for substance use disorders; 12-step groups. However, participants in this group do not receive treatment that is targeted at decreasing PTSD symptoms.
Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS). To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS.
Tetrahydrocurcumin (THC) and microglial polarization play crucial roles in neuroprotection during traumatic brain injury (TBI). However, whether THC regulates microglial polarization in TBI is unknown. Thus, we intended to analyze the functions and mechanism of THC in nerve injury after TBI via the regulation of microglial polarization. A TBI rat model was established, and modified neurological function score (mNSS), brain water content, Nissl staining, and Fluoro-Jade B (FJB) staining were used to evaluate neurological function. The expression of the M1-linked markers CD16 and CD86, as well as the M2-associated markers CD206 and YM-1, was analyzed via qRT-PCR, western blotting, and immunofluorescence. The levels of inflammatory cytokines were assessed via ELISA. Primary microglia were isolated from the brain and treated with lipopolysaccharide (LPS) to induce injury. TUNEL staining was used to measure primary microglial apoptosis. The expression of GSK3β, PTEN, and PI3K/Akt pathway proteins was detected via western blotting. TBI induced nerve injury, while THC improved neurological function recovery after TBI. Further analysis indicated that THC enhanced M2 microglial polarization and attenuated the inflammatory reaction mediated by microglia both in vitro and in vivo. Moreover, we found that THC promoted the M2 microglial phenotype through upregulating GSK3β expression. Additionally, we proved that GSK3β activated the PI3K/Akt pathway by phosphorylating PTEN. In conclusion, we demonstrated that THC protected against nerve injury after TBI via microglial polarization via the GSK3B/PTEN/PI3K/Akt signaling axis, suggesting the potential of THC for TBI treatment by promoting microglial M2 polarization.