anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This randomized, single-center phase 1/2a clinical trial, conducted without blinding, aims to explore the therapeutic promise of regulatory T cells (Tregs). Tregs are specialized immune cells that play a crucial role in modulating the body's immune response, thus offering a unique therapeutic avenue for immune-related conditions. They have already demonstrated significant potential in managing a spectrum of diseases, including autoimmune disorders such as multiple sclerosis and type 1 diabetes, inflammatory conditions like inflammatory bowel disease, and transplant rejection, which is commonly encountered in organ and stem cell transplants. The trial's primary focus is on graft-versus-host disease (GVHD), a severe complication that can occur after allogeneic hematopoietic stem cell transplantation (HSCT). GVHD emerges when the donated immune cells attack the recipient's tissues, leading to symptoms ranging from mild to life-threatening. Currently, GVHD treatment relies on broad immunosuppressive therapies, which often come with significant side effects and may not always be effective. By recruiting participants for this clinical trial, we aim to assess the safety and efficacy of Tregs in mitigating the immune system's attack on the recipient's body. Autologous Tregs offer a more targeted approach due to their ability to distinguish between harmful and beneficial immune responses, potentially reducing the need for broad immunosuppression. The trial's structure includes dose-escalation and dose-expansion phases to evaluate optimal dosages, assess any adverse reactions, and measure the therapeutic benefits in GVHD management. Through this systematic and thorough evaluation, the investigators hope to refine Treg therapy and establish a clear safety profile. Ultimately, this trial seeks to unlock the therapeutic potential of autologous Tregs, paving the way for future applications in a broader range of conditions.
OBJECTIVE: Diabetic neuropathic pain (DNP) is one of the most prevalent symptoms of diabetes. The alteration of proteins in the spinal cord dorsal horn (SCDH) plays a significant role in the genesis and the development of DNP. Our previous study has shown electroacupuncture could effectively relieve DNP. However, the potential mechanism inducing DNP's genesis and development remains unclear and needs further research.
METHODS: This study established DNP model rats by intraperitoneally injecting a single high-dose streptozotocin; 2 Hz electroacupuncture was used to stimulate Zusanli (ST36) and Kunlun (BL60) of DNP rats daily from day 15 to day 21 after streptozotocin injection. Behavioral assay, quantitative PCR, immunofluorescence staining, and western blotting were used to study the analgesic mechanism of electroacupuncture.
RESULTS: The bradykinin B1 receptor (B1R) mRNA, nuclear factor-κB p65 (p65), substance P, and calcitonin gene-related peptide (CGRP) protein expression were significantly enhanced in SCDH of DNP rats. The paw withdrawal threshold was increased while body weight and fasting blood glucose did not change in DNP rats after the electroacupuncture treatment. The expression of B1R, p65, substance P, and CGRP in SCDH of DNP rats was also inhibited after the electroacupuncture treatment.
CONCLUSION: This work suggests that the potential mechanisms inducing the allodynia of DNP rats were possibly related to the increased expression of B1R, p65, substance P, and CGRP in SCDH. Downregulating B1R, p65, substance P, and CGRP expression levels in SCDH may achieve the analgesic effect of 2 Hz electroacupuncture treatment.
The association of hypogonadism and cerebellar ataxia was first recognized in 1908 by Gordon Holmes. Since the seminal description, several heterogeneous phenotypes have been reported, differing for age at onset, associated features, and gonadotropins levels. In the last decade, the genetic bases of these disorders are being progressively uncovered. Here, we review the diseases associating ataxia and hypogonadism and the corresponding causative genes. In the first part of this study, we focus on clinical syndromes and genes (RNF216, STUB1, PNPLA6, AARS2, SIL1, SETX) predominantly associated with ataxia and hypogonadism as cardinal features. In the second part, we mention clinical syndromes and genes (POLR3A, CLPP, ERAL1, HARS, HSD17B4, LARS2, TWNK, POLG, ATM, WFS1, PMM2, FMR1) linked to complex phenotypes that include, among other features, ataxia and hypogonadism. We propose a diagnostic algorithm for patients with ataxia and hypogonadism, and we discuss the possible common etiopathogenetic mechanisms.
Aging entails changes at the cellular level that increase the risk of various pathologies. An association between gut microbiota and age-related diseases has also been attributed. This study aims to analyze changes in fecal microbiota composition and their association with genes related to immune response, gut inflammation, and intestinal barrier impairment. Fecal samples of female mice at different ages (2 months, 6 months, 12 months, and 18 months) and gene expression in colon tissue were analyzed. Results showed that the older mice group had a more diverse microbiota than the younger group. Additionally, the abundance of Cyanobacteria, Proteobacteria, Flavobacteriaceae, Bacteroides, Parabacteroides, Prevotellaceae_UCG-001, Akkermansia, and Parabacteroides goldsteinii increased with age. In contrast, there was a notable decline in Clostridiaceae, Lactobacillaceae, Monoglobaceae, Ligilactobacillus, Limosilactobacillus, Mucispirillum, and Bacteroides faecichinchillae. These bacteria imbalances were positively correlated with increased inflammation markers in the colon, including Tnf-α, Ccl2, and Ccl12, and negatively with the expression of tight junction genes (Jam2, Tjp1, and Tjp2), as well as immune response genes (Cd4, Cd72, Tlr7, Tlr12, and Lbp). In conclusion, high levels of diversity did not result in improved health in older mice; however, the imbalance in bacteria abundance that occurs with aging might contribute to immune senescence, inflammation, and leaky gut disease.
The invention provides a cosmetic composition which can smooth fine lines and wrinkles, impart firmness and elasticity to the facial skin, and make fine lines and wrinkles less noticeable, all within a short period of time. The cosmetic composition is in a hydrogel form and contains sodium hyaluronate, modified cornstarch, and pullulan, particularly in amounts of 0.1 to 1.0 wt. %, 0.5 to 5.0 wt. %, and 0.1 to 3.0 wt. %, respectively. The composition may further contain a dispersant.
India contributes to 26% of the global tuberculosis (TB) burden, with very high mortality and morbidity. The exact incidence of disseminated TB cannot be established among the general population but accounts for <2% of cases among immunocompromised hosts and constitutes 20% of all extrapulmonary TB cases. Disseminated TB has a very high mortality rate of around 25-30%. Miliary TB, a disseminated form, is another entity of TB that poses a health burden due to its difficulty in diagnosis. This entity usually presents with subclinical symptoms and poses a diagnostic challenge in the absence of specific diagnostic tests. We present a case of a young female with epistaxis and thrombocytopenia who was diagnosed with disseminated TB [miliary, bone cyst, bone marrow (BM) involvement].
A mixture of a glycoside derivative together with an isethionate in the presence of water gives a composition which is effective as a pearlescent agent. The mixture may be concentrated and contain as little as 35 % by weight of water. The relative proportions by weight of glycoside to isethionate to achieve a pearlescent effect are from 0.4:1 up to 1.5:1, preferably about 0.6:1 by weight. The glycoside is preferably an alkyl polyglucoside. The isethionate may be sodium cocoyl isethionate. The mixture may additionally contain anionic detergents such as sodium sulphosuccinate, sodium alkyl sulphate or sodium alkyl ether sulphate.
Protein interactions are fundamental for all cellular metabolic activities. Cytoplasmic linker protein 170 (CLIP170) plays diverse roles in cellular processes and the development of malignant tumors. Renal cell carcinoma (RCC) poses a significant challenge in oncology owing to its invasive nature, metastatic potential, high recurrence rates, and poor prognosis. However, the specific mechanisms and roles of CLIP170 underlying its involvement in RCC progression remain unclear. The findings of this study revealed a significant upregulation of CLIP170 in RCC tumor tissues. Elevated CLIP170 expression correlated positively with advanced clinical and pathological stages and was associated with poor overall survival in RCC patients. Functional assays in vitro demonstrated that elevated CLIP170 levels enhanced RCC cell proliferation, migration and invasion. Mechanistically, 4D-label free proteomics library identified that CLIP170 increased the level of FOSL1 in the Wnt signaling pathway. Immunoprecipitation and molecular docking were performed to unveil that CLIP170 formed a complex with β-catenin, inhibiting β-catenin degradation via the ubiquitin-proteasome pathway. Elevated β-catenin levels within RCC cells played a central role in promoting the transcriptional expression of FOSL1, thereby facilitating RCC cell proliferation and epithelial-mesenchymal transition (EMT) progression. In vivo investigations corroborated these findings, illustrating that CLIP170 regulated β-catenin and FOSL1 expression, driving tumor growth in RCC. This study highlights the crucial role of CLIP170 in promoting FOSL1 expression by preventing β-catenin ubiquitination and degradation, thus promoting RCC tumor progression. It suggests the CLIP170/β-catenin/FOSL1 axis as a potential therapeutic target for RCC treatment.
The invention relates to a composition with an effect of preventing multiple infections. The composition comprises the active ingredients of indigowoad root, dandelion, honeysuckle flower and sweet tea in the weight ratio of (5-20):(2-10):(1-5):(1-2). The composition provided by the invention combines indigowoad root, dandelion, honeysuckle flower and sweet tea for using together. On the one aspect, through the effects of clearing away heat and toxic materials, relieving pain, relieving fever, resisting inflammation, calming mind, promoting blood circulation, removing blood stasis, inducing diuresis, eliminating swelling and the like, the immune function of a human body is regulated, the anti-infection ability of the human body is strengthened and the inflammation is eliminated. On the other aspect, the anti-infection effect is realized by direct sterilization, bacteriostasis and anti-viral action, so that the composition is effective for viral influenza, measles, mumps, cold and influenza and can also be used for treating the inflammation caused by bacteria and part of other microbial infections. The composition can treat both manifestation and root cause and has obvious effects on inhibiting and killing a variety of viruses and pathogenic bacteria. The invention further provides a method for preparing the composition with the effect of preventing multiple infections.
BACKGROUND: Timely and accurate prediction of disease progress is crucial for facilitating early intervention and treatment for various chronic diseases. However, due to the complicated and longitudinal nature of disease progression, the capacity and completeness of clinical data required for training deep learning models remains a significant challenge. This study aims to explore a new method that reduces data dependency and achieves predictive performance comparable to existing research.
METHODS: This study proposed DAPNet, a deep learning-based disease progression prediction model that solely utilizes the comorbidity duration (without relying on multi-modal data or comprehensive medical records) and disease associations from biomedical knowledge graphs to deliver high-performance prediction. DAPNet is the first to apply multi-view graph contrastive learning to disease progression prediction tasks. Compared with other studies on comorbidities, DAPNet innovatively integrates molecular-level disease association information, combines disease co-occurrence and ICD10, and fully explores the associations between diseases; RESULTS: This study validated DAPNet using a de-identified clinical dataset derived from medical claims, which includes 2,714 patients and 10,856 visits. Meanwhile, a kidney dataset (606 patients) based on MIMIC-IV has also been constructed to fully validate its performance. The results showed that DAPNet achieved state-of-the-art performance on the severe pneumonia dataset (F1=0.84, with an improvement of 8.7%), and outperformed the six baseline models on the kidney disease dataset (F1=0.80, with an improvement of 21.3%). Through case analysis, we elucidated the clinical and molecular associations identified by the DAPNet model, which facilitated a better understanding and explanation of potential disease association, thereby providing interpretability for the model.
CONCLUSIONS: The proposed DAPNet, for the first time, utilizes comorbidity duration and disease associations network, enabling more accurate disease progression prediction based on a multi-view graph contrastive learning, which provides valuable insights for early diagnosis and treatment of patients. Based on disease association networks, our research has enhanced the interpretability of disease progression predictions.
All patients of the study population with a record/diagnosis of a first fracture of the hip or femur during the study period regardless of whether they have a history of past fractures. When the patient has a history of hip or hip/femur fracture, a minimum of 12 months should have elapsed between the two episodes for a current fracture to be considered a new event.
Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.
Ruxolitinib 20mg BID plus Duvelisib 25mg, 50mg, or 75mg BID. Patients will be instructed to take duvelisib and ruxolitinib by mouth every 12 hours, the same time each day, +/- 2 hours. Duvelisib and ruxolitinib will be provided via the institutional investigational pharmacy. The researchers will utilize a dose-escalation standard 3+3 design in which we evaluate 3 doses of duvelisib (25mg BID, 50mg BID, and 75mg BID) in combination with ruxolitinib 20mg BID. A minus-1 dose level of duvelisib (15mg BID) can be used if de-escalation is needed. The cohort expansion phase will have two treatment groups JAK/STAT activation or mutation present or JAK/STAT activation or mutation absent or unknown. Upon discussion with PI, the treating physician may increase dose up to 20 mg of ruxotlinib and/or 25 mg of duvelisib when deemed clinically favorable.
OBJECTIVE: The aim of this study was to evaluate the prevalence of early neonatal sepsis in pregnant women with a positive culture for group B beta-hemolytic Streptococcus in a middle-income city in Southeastern Brazil.
METHODS: A retrospective cohort study was conducted, involving singleton low- and high-risk pregnancies in whom group B beta-hemolytic Streptococcus cultures were evaluated between 35 and 37 weeks of gestation using vaginal and anal swabs. A specific medium (Todd-Hewitt) was used for culturing. The pregnant women were divided into two groups based on positive (n==201) and negative (n==420) cultures for group B beta-hemolytic Streptococcus.
RESULTS: The maternal colonization rate by group B beta-hemolytic Streptococcus was 32.3%. The prevalence of early neonatal sepsis was 1.0% (2/201) among patients with a positive group B beta-hemolytic Streptococcus culture and 1.9% (8/420) among patients with a negative culture. Among the patients who underwent adequate prophylaxis, crystalline penicillin G was used in 51.9% (54/104), followed by cefazolin in 43.3% (45/104), ampicillin in 3.8% (4/104), and clindamycin in 1.0% (1/104). A model that included prematurity (p==0.001) proved to be an independent risk predictor of early neonatal sepsis [χ2 (1)==15.0, odds ratio: 16.9, 95% confidence interval: 4.7-61.6, p<0.001, Nagelkerke R2==0.157].
CONCLUSION: The prevalence of a positive culture for group B beta-hemolytic Streptococcus was high. However, the prevalence of early neonatal sepsis was low in pregnant women with both positive and negative group B beta-hemolytic Streptococcus cultures and in pregnant women with a positive culture who underwent both adequate and inadequate antibiotic prophylaxis. Prematurity proved to be an independent predictor of early neonatal sepsis, considering the entire study population.
UNLABELLED: Defining the initial events in oncogenesis and the cellular responses they entrain, even in advance of morphologic abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this, we longitudinally studied the changes induced by loss of the tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. Vhl inactivation was directly coupled to expression of a tdTomato reporter within a single allele, allowing accurate visualization of affected cells in their native context and retrieval from the kidney for single-cell RNA sequencing. This strategy uncovered cell type-specific responses to Vhl inactivation, defined a proximal tubular cell class with oncogenic potential, and revealed longer term adaptive changes in the renal epithelium and the interstitium. Oncogenic cell tagging also revealed markedly heterogeneous cellular effects including time-limited proliferation and elimination of specific cell types. Overall, this study reports an experimental strategy for understanding oncogenic processes in which cells bearing genetic alterations can be generated in their native context, marked, and analyzed over time. The observed effects of loss of Vhl in kidney cells provide insights into VHL tumor suppressor action and development of renal cell carcinoma.
SIGNIFICANCE: Single-cell analysis of heterogeneous and dynamic responses to Vhl inactivation in the kidney suggests that early events shape the cell type specificity of oncogenesis, providing a focus for mechanistic understanding and therapeutic targeting.
AIM: To report the clinical outcomes of thoracoscopic left atrial appendage occlusion (LAAO) with the AtriClip PRO2 device (Atricure Inc, Mason, OH, USA). Stroke risk reduction with LAAO in patients with atrial fibrillation is now well-established. Many surgical and percutaneous techniques have been used, with varying rates of success. The percutaneous devices have had issues with procedural complications and peridevice flow. Thoracoscopic AtriClip offers an epicardial linear closure of the appendage at its ostium. This study sought to evaluate its safety and efficacy in achieving complete LAA closure.
METHOD: This is a prospective series of thoracoscopic AtriClip PRO2 as a standalone procedure or a thoracoscopic AtriClip deployed as an adjunct to minimal access cardiac and thoracic surgery. Study ethical approval was granted by the hospital Human Research Ethics Committee.
RESULTS: In total, 144 thoracoscopic AtriClip procedures were conducted by a single surgeon from 2017 to 2022, 56 standalone and 88 concomitant. There was no mortality or major morbidities. A 100% success in complete LAA closure was observed, with 87% complete follow-up imaging. For patients that underwent standalone AtriClip after cessation of anticoagulation, no thromboembolic phenomena were seen in the 180 patient-years of follow-up.
CONCLUSIONS: This study demonstrates that thoracoscopic placement of AtriClip is safe and effective in achieving consistent and complete LAAO. Future randomised trials will be useful to compare outcomes with percutaneous devices.
Patients receive cisplatin and undergo EBRT followed by brachytherapy as in Arm I. Patients also receive triapine IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Treatment continues in the absence of disease progression or unacceptable toxicity.
Hypotension is common in patients who undergo general anesthesia. Hypotension may cause hypoperfusion in the organs of the body, resulting in ischemia and increased mortality within one year. Hypotension may occur at any time during general anesthesia but may also occur with changes in posture. In robot-assisted laparoscopic radical prostatectomy, hypotension often occurs when posture is changed from a Trendelenburg position to a supine position. However there is no data regarding which hemodynamic parameters can predict hypotension induced by position change.

Excessive administration of the fluid in steep Trendelenburg position may lead to fluid overload and lead to complications such as pulmonary edema. Thus, the predictors are should be identified to manage patients without fluid overload. Therefore, the aim of this study is to investigate the parameters of Cardio Q which are useful for predicting hypotension after position change.
Oprozomib 300 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason.
<P>PROBLEM TO BE SOLVED: To provide a formulation for therapeutic use for improving delivery efficiency of introduced genes.  <P>SOLUTION: Aqueous and nonaqueous solution formulations contain agents useful for treating cancer. In one aspect, a pharmaceutical composition provided contains SYN3 in combination with a pharmaceutically acceptable carrier. In another aspect, a pharmaceutical composition provided contains SYN3 in combination with a pharmaceutically acceptable nonaqueous carrier. In another aspect, a pharmaceutical composition provided contains SYN3 in combination with a pharmaceutically acceptable aqueous carrier. In another aspect, a pharmaceutical composition provided contains SYN3 in combination with a pharmaceutically acceptable carrier and at least one pharmaceutically acceptable solubilizing agent.  <P>COPYRIGHT: (C)2010,JPO&INPIT