anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The present invention relates to a genetically engineered, CD19-specific chimeric T cell receptor and to immune cells expressing the chimeric receptor. The present invention also relates to the use of such cells for cellular immunotherapy of CD19<SUP>+</SUP> malignancies and for abrogating any untoward B cell function. The chimeric receptor is a single chain scFvFc:zeta receptor where scFvFc designates the extracellular domain, scFv designates the V<SUB>H </SUB>and V<SUB>L </SUB>chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG<SUB>1</SUB>, and zeta represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain zeta are linked by a transmembrane domain such as the transmembrane domain of CD4. In one aspect, the chimeric receptor comprises amino acids 23-634 of SEQ ID NO:2. The present invention further relates to a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor.
PURPOSE: To obtain an acylaminoaldehyde derivative, excellent in oral absorbability and cell membrane permeability, having inhibiting actions on cysteine proteases and useful for preventing and treating osteopathy. CONSTITUTION: This compound of formula I (Q is a direct bond or one or two amino acid residues, etc., in which the amino acid residues are α-amino acids; R<1> is a hydrocarbon, a heterocyclic group, etc.; R<4> is carboxyl group, etc., which may be esterified; X is a 1-4C alkylene, etc.), e.g. N-t- butoxycarbonyl-(L)-phenylalanyl-(L)-tryptophanol. The compound of formula I is obtained by reacting a compound of formula II, e.g. benzyloxycarbonyl-(L)- tryptophanol with an acetaldehyde derivative and further carrying out the reducing reaction of the resultant compound. In the process, the reducing reaction is preferably carried out in the presence of a catalyst such as an Ni compound in a solvent such as methanol at 10-80 deg.C under 1-150atm for 0.5-50hr.
Dengue fever, an infectious disease prevalent in subtropical and tropical regions, currently lacks effective small-molecule drugs as treatment. In this study, we used a fluorescence peptide cleavage assay to screen seven compounds to assess their inhibition of the dengue virus (DENV) NS2B-NS3 protease. DV-B-120 demonstrated superior inhibition of NS2B-NS3 protease activity and lower toxicity compared to ARDP0006. The selectivity index of DV-B-120 was higher than that of ARDP0006. In vivo assessments of the antiviral efficacy of DV-B-120 against DENV replication demonstrated delayed mortality of suckling mice treated with the compound, with 60-80% protection against life-threatening effects, compared to the outcomes of DENV-infected mice treated with saline. The lower clinical scores of DENV-infected mice treated with DV-B-120 indicated a reduction in acute-progressive illness symptoms, underscoring the potential therapeutic impact of DV-B-120. Investigations of DV-B-120's ability to restore the antiviral type I IFN response in the brain tissue of DENV-infected ICR suckling mice demonstrated its capacity to stimulate IFN and antiviral IFN-stimulated gene expression. DV-B-120 not only significantly delayed DENV-2-induced mortality and illness symptoms but also reduced viral numbers in the brain, ultimately restoring the innate antiviral response. These findings strongly suggest that DV-B-120 holds promise as a therapeutic agent against DENV infection and highlight its potential contribution in addressing the current lack of effective treatments for this infectious disease.IMPORTANCEThe prevalence of dengue virus (DENV) infection in tropical and subtropical regions is escalating due to factors like climate change and mosquito vector expansion. With over 300 million annual infections and potentially fatal outcomes, the urgent need for effective treatments is evident. While the approved Dengvaxia vaccine has variable efficacy, there are currently no antiviral drugs for DENV. This study explores seven compounds targeting the NS2B-NS3 protease, a crucial protein in DENV replication. These compounds exhibit inhibitory effects on DENV-2 NS2B-NS3, holding promise for disrupting viral replication and preventing severe manifestations. However, further research, including animal testing, is imperative to assess therapeutic efficacy and potential toxicity. Developing safe and potent treatments for DENV infection is critical in addressing the rising global health threat posed by this virus.
Denosumab 120 mg sc on day -15, -8 and day 1, followed by Denosumab 120 mg sc q4wks + platinum based drugs q3wks + Gemcitabine 1250 mg/sm day 1,8 q3wks for 6 cycles. Denosumab 120 mg sc q4wks will continue for 12 months since chemotherapy end.
Transfusion-related acute lung injury (TRALI) is the leading cause of blood product related death. The precise mechanisms of TRALI are uncertain. We hypothesize that TRALI is a full spectrum of lung injury. One theory holds that the infusion of cytokines associated with the transfusion of stored blood combined with the trauma and stress of surgery produce lung injury. We propose to examine lung function following transfusion, and that stored blood (and by implication, cytokines) injures the lung. TRALI is a rare condition and we do not expect any of the patients that we observe will develop TRALI. We are merely observing their pulmonary function closely to see if there are any mild changes.

Patients will be randomized into three groups based on whether or not they have pre-donated blood for the surgery. Once divided into these groups they are randomized to one of three groups with patients in the first group randomized to receive their stored (either autologous or allogeneic) "unwashed" blood first in the operating room using the standard cell salvage system. The second group will receive their stored (either autologous or allogeneic) "washed" blood first and the third group will receive blood from the cell salvage system first. Those who get the stored blood first will get the cell salvage blood as their second transfusion and those that get the cell salvage blood first will get stored "unwashed" blood as the second transfusion in the operating room. We will closely monitor pulmonary function and oxygenation, and try to observe whether there is early evidence of lung changes. If there is evidence of lung changes, then the blood is tested for cytokines and antibodies.
INTRODUCTION: Few studies have examined the use of ibutilide in noncardiac surgical populations. Our study considered the effectiveness and safety of ibutilide in cardioversion of atrial fibrillation (AF) in medical and surgical intensive care patients.
METHODS: A retrospective chart review was performed for patients with a confirmed diagnosis of AF who were hemodynamically stable and received ibutilide after the initial diagnosis. Patients were administered 1 mg of ibutilide fumarate intravenous for 10 min with a second dose administered if AF persisted after 30 min. Patients were pretreated with intravenous magnesium sulfate if their blood magnesium level was <2 mg/dL.
RESULTS: Fifty seven total female patients and 99 male patients received ibutilide. Females had an 88% conversion rate to normal sinus rhythm (NSR) compared to 68% in males (P = 0.008). A 70% successful return to NSR was observed in patients from all groups pretreated with magnesium sulfate (P = 0.045). One year after discharge, 74% of the patients stayed in the NSR.
CONCLUSIONS: Within our population, pretreatment with magnesium sulfate followed by ibutilide was associated with increased conversion to NSR. Additionally, we noted that females had a higher conversion rate to NSR compared to males, regardless of whether they were pretreated with magnesium sulfate.
The present disclosure relates to a computer training system (100) for determining which stage a user performance belongs to. The system (100) is arranged to present multiple trials. The system (100) is arranged to receive user input to each trial at a respective time instant. The user input is associated with a first type and a second type of user improvement. The system (100) is arranged to determine a user performance at each time instant. The user performance comprises a first stage or a second stage of user performance. The first stage comprises the first type and the second type of user improvement. The second stage comprises the second type of user improvement, but not the first type. The system (100) is arranged to determine an indication of whether the user performance at each time instant belongs to the first stage or the second stage of user performance.
The incidence of non-melanoma skin cancers, i.e. basal cell and squamous cell carcinoma (BCC and SCC), in the US is over 5.4 million. Of these, BCC represents the majority, with an incidence of over 4 million. Recent guidelines published on the treatment of BCC and SCC establish Mohs micrographic surgery (MMS) as the treatment of choice for high-risk SCCs and BCCs and for those in cosmetically sensitive locations.

MMS involves the step-wise removal and subsequent histological examination of thin layers of cancer containing skin until only cancer-free tissue remains. At the initial layer, only clinically involved skin is excised. The excised tumor is oriented using purposeful marks on the tissue and color-coding. Using this orientation, a "Mohs map" is drawn to indicate where malignancy is seen histologically. For each following layer, orientation is maintained, and only margins with remaining malignant tissue are removed as indicated on the map. As the goal is to spare as much normal tissue as possible, Mohs layers are only a few millimeters thin. The average number of layers needed to remove an entire tumor per Mohs case is cited as 1.74. However, outlier providers - that take a fewer or higher number of layers to clear a cancer- do exist. While this could represent providers who see more complicated cases, and skin tumors are often more extensive than initially clinically apparent, the need to balance efficiency with the width of a layer likely also plays a role.

Fluorescence image guided surgery using Indocyanine green (ICG), an FDA approved near-infrared (NIR) dye, has been used for effective visualization of intra-osseous tumoral tissues in real-time, allowing surgeons to make intraoperative decisions for further resection of otherwise clinically-uninvolved tissue. The use of intradermal ICG in a cutaneous tumor during MMS could allow surgeons to directly visualize, and roughly map the extent of a primary skin cancer preoperatively and plan the Mohs procedure (i.e. the initial excision size and subsequent layer widths) accordingly. No current such mapping system exists for use in cutaneous tumors.

Thus, while MMS represents an effective methodology to remove malignant tissue and spare as much normal skin as possible, it is a lengthy process totaling several hours, and given the need for histological processing at each stage, its duration primarily correlates with the number of layers or stages needed. A pre-operative map of the extent of the tumor could allow for: (1) a larger first layer - on the initial excision, only clinically evident tumor is excised, but skin tumors are at times more extensive that clinically apparent; and the Mohs surgeon to take thicker subsequent layers as needed. Effective and accurate pre-operative tumor mapping with ICG therefore has the potential to reduce the total number of Mohs layers taken for a patient. This is effect would improve patient safety and quality of care, and reduce unnecessary financial burden associated with outliers. As a decreased number of layers would directly shorten the total procedure length, preoperative mapping also has the potential to help increase patient access to MMS.
PROBLEM TO BE SOLVED: To provide an oily cosmetic improved in storage stability and sense of use even when an oily component having low compatibility is contained in a constituent component.SOLUTION: There is provided an oily cosmetic which comprises components (A) to (C) and is composed of a continuous phase and a dispersed phase containing an encapsulated material having a core-shell structure. (A) One or more oily components which are liquid at 25°C and form a continuous phase in the cosmetic. (B) One or more oily components which are solid at 25°C and form a shell in an encapsulated material. (C) One or more oily components which are liquid or solid at 25°C and form a core in an encapsulated material. The solidification temperature of (C) is lower than the solidification temperature of (B). The phase separation temperature between (A) and (C) is higher than the solidification temperature of (B) and higher than at least one of the phase separation temperature between (A) and (B) and the phase separation temperature between (B) and (C).SELECTED DRAWING: Figure 1
According to the assumptions of psychoneuroimmunology, the improvement of mental state affects the physical improvement of patients. Numerous studies confirm the effectiveness of hypnosis and learning autohypnosis in improving the functioning of patients in terms of reducing pain and anxiety, improving the quality of sleep and mood. The study is a Prospective Randomized Controlled Trial consisting of two groups. Patients in the study group will receive a voice recording with hypnotic instructions with a suggestion to improve the psychophysical state. Patients in the control group will receive a recording with relaxing music. Depending on the randomization, patients will listen to the selected recording before being admitted to the surgical department. They will then be given a recording to listen to whenever they want. The patients will be examined four times using the Activity Change Scale, ie. before randomization, on the first day after surgery, on the 7th day after surgery and 1 month after surgery. Simultaneously the total analgesic consumption will be recorded.
INTRODUCTION: Type II endoleaks (T2ELs) following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) can lead to aneurysm growth, compromising the stent graft seal and risking rupture. Preventing these endoleaks during EVAR involves filling the AAA sac around the stent graft to exclude the aneurysm and block any arteries causing the endoleak. This study investigates the feasibility and safety of using AneuFix, a biocompatible injectable polymer developed by TripleMed (Geleen, the Netherlands), for aneurysmal sac filling during EVAR in high-risk T2EL patients.
METHODS AND ANALYSIS: A feasibility, single-arm, single-centre clinical trial will initially include five patients with infrarenal AAA, eligible for EVAR, and at high risk for T2EL based on the number of patent lumbar arteries and the cross-sectional area of the aortic lumen at the level of the inferior mesenteric artery. Postevaluation by the Data Safety and Monitoring Board, the study cohort will extend to 25 patients. During EVAR and after stent graft deployment, the aneurysm sac is filled with AneuFix polymer using a filling sheath positioned parallel to the contralateral limb with the tip inside the aneurysm sac. Primary outcome is technical success (successful AAA sac filling). The secondary outcomes include clinical success at 6 and 12 months (occurrence of T2ELs and AAA growth assessed with CT angiography), intraoperative and perioperative complications, all endoleaks, adverse events, re-interventions, aneurysm rupture and patient survival.
ETHICS AND DISSEMINATION: This trial was approved by the Dutch Authorities (Central Committee on Research Involving Human Subjects, IGJ), Amsterdam University Medical Centre Ethical Commission, and adheres to the Declaration of Helsinki and European Medical Device Regulation. Results will be shared at (inter)national conferences and in peer-reviewed journals.
TRIAL REGISTRATION NUMBER: NCT04307992.
Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable. Daclizumab is a humanized anti-Tac monoclonal antibody directed against the high affinity IL-2 receptor CD25 or Tac subunit. The IL-2 receptor system plays a central role in the induction of immune responses via activated T and B-lymphocytes, observed both in uveitis animal models and on the surface of human cells in patients with uveitis. Blocking this system impedes immune responses and can inhibit the development of local inflammatory responses. Previous studies using intravenous daclizumab treatments suggest that continuing daclizumab treatments at 1 mg/kg every 2-4 weeks may effectively control uveitis even after the complete withdrawal of standard immunosuppressive medications. Subcutaneous (SC) daclizumab injections at 1 and 2 mg/kg in healthy volunteers are well tolerated and have been shown to produce serum daclizumab trough levels comparable to intravenous treatments.

This is an open-label, multi-center Phase II trial of SC daclizumab designed to provide information on current trial design feasibility as well as preliminary safety and efficacy data on 15 participants at 3 sites who are 6 years of age or older and who require standard systemic immunosuppression to control their non-infectious posterior or intermediate uveitis. The SC daclizumab treatments are given every 2 weeks for up to 6 months unless a safety endpoint requires study exit. A re-induction of SC daclizumab therapy may be permitted after an initial efficacy failure. Therapy begins with two induction treatments at 2 mg/kg (limit of 200 mg), followed by maintenance therapy at 1 mg/kg (limit of 100 mg). Beginning with the first SC daclizumab treatment, the initial immunosuppressive medication load will be tapered in a staggered fashion to a target level of 50% or less of the original dose within an 8 to 12-week period, if tolerated. After a preliminary efficacy evaluation at 12 weeks, further tapering and continued SC daclizumab therapy may continue as clinically indicated through the duration of the trial. The primary efficacy outcome is the maintenance of visual acuity with the simultaneous reduction of original immunosuppressive medication load. Primary safety measures are visual acuity and the occurrence of adverse events. Secondary outcome measures include anterior chamber and vitreous cells, vitreous haze, and questionnaire results.
Broadly, the goal of Introspect Health is to shift clinical practice from reactively treating psychiatric disorders and mental health issues once manifested to a preventative care model for integrative mental health in a way that is cost-effective and scalable. One of the principal areas of struggle in preventative mental health is self-report adherence and the ability for primary care physicians and non-psychiatrists to perform mental health surveillance with their patients. This study specifically examines the relationship between individuals and a novel self-report assessment tool. To do this, the investigators are performing a randomized controlled trial with two classes of users (the general public and patients undergoing treatment for mental health issues) for a six week trial comparing the novel self-report assessment tool to the standard of care assessment tools available to clinicians. Participants will be randomized to one of the two daily assessment regiments within the internet-delivered assessment tool: one that is representative of standard of care monitoring and one that is personalized both in terms of content and timing based on the participant's intake as well as ongoing participation. Neither the participants nor researcher will be aware of which arm the individual is randomized. After using the software for six weeks, the data will be analyzed specifically targeting self-adherence and assessment completion metrics to evaluate the potential benefits of a transdiagnostic assessment system over the standard-of-care monotopic assessment system. Assessment scoring is handled by an automated scoring engine, using the rules set forth by the standards in the assessment protocols. The study does not test the efficacy of the personalized assessments as a diagnostic instrument, there is no clinical decision support provided to clinicians during this study, and there is no treatment provided during this study.
Graves' disease (GD) is an autoimmune condition that can progress to Graves' ophthalmopathy (GO), leading to irreversible damage to orbital tissues and potential blindness. The pathogenic mechanism is not fully understood. In this study, we conducted single-cell multi-omics analyses on healthy individuals, patients with GD without GO, newly diagnosed patients with GO, and treated patients with GO. Our findings revealed gradual systemic inflammation during GO progression, marked by overactivation of cytotoxic effector T cell subsets, and expansion of specific T cell receptor clones. Importantly, we observed a decline in the immunosuppressive function of activated Treg (aTreg) accompanied by a cytotoxic phenotypic transition. In vitro experiments revealed that dysfunction and transition of GO-autoreactive Treg were regulated by the yin yang 1 (YY1) upon secondary stimulation of thyroid stimulating hormone receptor (TSHR) under inflammatory conditions. Furthermore, adoptive transfer experiments of the GO mouse model confirmed infiltration of these cytotoxic Treg into the orbital lesion tissues. Notably, these cells were found to upregulate inflammation and promote pathogenic fibrosis of orbital fibroblasts (OFs). Our results reveal the dynamic changes in immune landscape during GO progression and provide direct insights into the instability and phenotypic transition of Treg, offering potential targets for therapeutic intervention and prevention of autoimmune diseases.
At present there is no curative treatment for post-acute COVID-19 syndrome (PACS). Treatment is focused on symptom management and individualized rehabilitation. There is data indicating SARS-CoV-2 viral persistence and chronic immune system activation in PACS. We are proposing an interventional, randomized and placebo-controlled clinical intervention trial of nirmatrelvir/ritonavir (300/100 mg) or placebo/ritonavir (100mg), twice daily for 15 days, in patients suffering from severe PACS and meeting the WHO definition of severe PACS. A total of 180 patients will be enrolled in this study and these will be randomized in a 2:1 ratio to receive either nirmatrelvir/ritonavir or placebo/ritonavir. The study will include deep exploratory systems-level analyses of the immune system in PACS patients, including changes induced by nirmatrelvir/ritonavir (Paxlovid®) treatment. The purpose of this study is to evaluate the efficacy of nirmatrelvir/ritonavir for its potential ability to provide sustained improvement in quality of life, in non-hospitalized patients with post-COVID, a patient group with high unmet medical needs.

Hypothesis: Nirmatrelvir/ritonavir (Paxlovid®) improves health-related quality of life measured using the EQ-5D-5L VAS scale, as compared to placebo/ritonavir, in objective and pre-defined clinical phenotypes: postural orthostatic tachycardia syndrome (POTS), microvascular dysfunction, inappropriate sinus tachycardia, persistent fever, post exertional malaise (PEM), fatigue, brain fog, dyspnea, dysfunctional breathing patterns or inflammatory phenotypes (increased plasma D-dimer, CRP, ESR and ferritin).