anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions.
OBJECTIVES: I. Define the maximum tolerated dose (MTD) of paclitaxel (TAX) when given as a 3 hour infusion in combination with cisplatin (CDDP), fluorouracil (5-FU), and radiation therapy. II. Define the toxicity profile of TAX when given as a 3 hour infusion in combination with CDDP, 5-FU, and radiation therapy. III. Evaluate the effectiveness of a TAX containing chemotherapy regimen and concurrent radiotherapy followed by resection in the treatment of locally advanced esophageal cancer as judged by the complete response rate, pathological complete response rate, time to recurrence, and overall survival.

OUTLINE: Patients receive radiation to the tumor and nodal area 5 days a week for 5 weeks. Patients receive chemotherapy consisting of cisplatin (CDDP) via rapid intravenous infusion on day 1 followed by fluorouracil (5-FU) via 96-hour continuous infusion (CI) on days 1 through 4; this is repeated on the last 4 days of radiation therapy (days 29-31), with an additional dose of CDDP on day 29 and a 96-hour CI of 5-FU on days 29-31. Patients also receive paclitaxel (TAX) as a weekly 3 hour infusion on days 1, 8, 15, and 29, with 3 patients treated at each dose level and subsequent patients treated according to the toxicity observed in previous cohorts. TAX will be given prior to the CDDP and 5-FU on the weeks when it is given concurrently. The MTD of TAX is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. Surgical resection takes place 2-8 weeks following completion of chemoradiotherapy in all patients except those with disease progression and those who are surgically unresectable or medically unfit (includes those with metastatic disease) to tolerate surgery. An additional course of TAX/CDDP/5-FU is given 28-35 days after surgery.

PROJECTED ACCRUAL: Three patients will be entered into the lowest dose level of TAX, and 3-6 patients entered into up to three additional dose levels of TAX for the phase I study. An additional group of up to 11 patients will be accrued for the first stage of the modified phase II study and 38 to the second stage, if warranted. The study will be completed within 3-4 years.
Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins. Patients with advanced solid tumors and relapsed/refractory (R/R) B-cell lymphomas were enrolled in an open label, phase I dose escalation trial of oral daily zelenirstat, administered in 28-day cycles until progression or unacceptable toxicity. The endpoints were to evaluate dose-limiting toxicities (DLT) to establish a maximum tolerated dose (MTD), pharmacokinetic parameters, and anticancer activity. Twenty-nine patients were enrolled (25 advanced solid tumor; 4 R/R B-cell lymphoma) and 24 were DLT-evaluable. Dosing ranged from 20 mg once daily (OD) to 210 mg OD without DLT, but gastrointestinal DLTS were seen in the 280 mg cohort. MTD and recommended phase 2 dose were 210 mg OD. Common adverse events were predominantly Gr ≤ 2 nausea, vomiting, diarrhea, and fatigue. Plasma concentrations peaked at 2 h with terminal half-lives averaging 10 h. Steady state was achieved by day 15, and higher doses achieved trough concentrations predicted to be therapeutic. Stable disease as best response was seen in eight (28%) patients. Progression-free survival and overall survival were significantly better in patients receiving 210 mg OD compared to those receiving lower doses. Zelenirstat is well-tolerated, achieves plasma exposures expected for efficacy, and shows early signs of anticancer activity. Further clinical development of zelenirstat is warranted.
BACKGROUND: Transient urinary incontinence (UI) is distressing event following holmium laser enucleation of the prostate (HoLEP). Novel technique namely, veil sparing HoLEP (VS-HoLEP), was proposed to improve early continence outcome. In this trial (NCT03494049), VS-HoLEP was compared to standard HoLEP (St-HoLEP).
METHODS: VS-HoLEP entails early apical separation with sparing of ventral apical mucosal veil proximal to the verumontanum. Eligible symptomatic BPH patients were randomly allocated to St-HoLEP (91) and VS-HoLEP (89). The primary outcome was UI as depicted by one-hour pad test at one month postoperatively. Other outcome measures include all perioperative parameters, complications, and urinary outcome measures at different follow-up points.
RESULTS: Median preoperative prostate size was 138 (50:282) and 128 (50:228) mL in St-HoLEP and VS-HoLEP groups respectively. At one month the number of patients with positive one-hour pad test was 21 (23.1%) and 10 (11.4%) in St-HoLEP and VS-HoLEP groups respectively (P 0.047). The difference was significantly in favor of VS-HoLEP considering the number of patients reporting UI, the number of patients with positive one-hour pad test as well as the grade of UI reported at one and 4 months. The difference was not statistically significant at 12 months. The median time to patients' reported continence was 8 (1-52) and 1.5 (1-52) weeks in St-HoLEP and VS-HoLEP groups respectively (P≤0.005). The technique independently predicted positive one-hour pad test at one and four months respectively. At twelve months presence of DM (diabetes mellitus) and more percent PSA reduction independently predicted positive one-hour pad test.
CONCLUSIONS: Veil sparing HoLEP enhances significantly early postoperative urine continence both subjectively and objectively. Optimization of the surgical technique could cut short the number of leaking patients and reduce the degree as well as the duration of transient postoperative urine leak.
The present invention provides globeflower injectable powder and a preparation method thereof, which comprises the injectable powder prepared from four traditional Chinese medicines mainly including globeflower, a composition formula and a preparation method thereof. The globeflower injectable powder contains chlorogenic acid, vitexin, orientoside, crysanthemum indicum lctone, artoglasin and baicalin. The composition formula comprises (by weight) 3 to 5 parts of globeflower, 2 to 4 parts of honeysuckle flower, 1 to 3 parts of scutellaria roots and 1 to 3 parts of chrysanthemi indici. The preparation method comprises: preparing a globeflower extract with a water-alcohol method, preparing a scutellaria root extract with an acid-alkali method, mixing the two extracts to prepare a semi-finished solution of the globeflower injectable powder, filtering the solution, adding injection water, regulating pH to 7 with a 35 to 40% sodium hydroxide solution, treating the semi-finished solution with a freeze drying or spray drying method to obtain the globeflower injectable powder. The four traditional Chinese medicines jointly perform the functions of clearing heat and toxic material, leaking fire and relieving sore-throat. Thus, the globeflower injectable powder is used for swelling and sore throats, upper respiratory tract infections, tonsillitis, pestilence and influenza, and provides a new antiinflammation antiviral medicine for Chinese traditional treatment on emergency and severe cases.
<P>PROBLEM TO BE SOLVED: To obtain a hair grower which has good preparation stability and can exhibit an excellent hair-growing effect without causing a problem such as an undesired side effect or scalp irritation.  <P>SOLUTION: This hair grower contains a Nasturtium officinale R. Br. extract, or one or more of the steam distillation water of the flowers of a plant belonging to the genus Citrus and the juice of the plant belonging to the genus Citrus as a vascular endothelial cell growth factor (VEGF) production promoter. Consequently, an excellent hair-growing effect can be obtained by the promotion of hair follicles from their resting stage to their growing stage and by the extension of the hair follicle-growing stage. In addition, the hair grower capable of reinforcing the hair-growing effect contains the Nasturtium officinale R. Br. extract in addition to one or more of the steam distillation water of the flowers of a plant belonging to the genus Citrus and the juice of the plant belonging to the genus Citrus.  <P>COPYRIGHT: (C)2004,JPO
Patients received pulsed laser treatment, using a HIRO 3 device (ASA Laser, Arcugnano, Italy), five times a week for a period of four weeks, and one session per day for a total of 20 sessions. A 3-phase treatment program was performed in each session, and the patients were then given a daily exercise program once a day by a physiotherapist.
After radical surgery for breast cancer, screening to diagnose recurrence in asymptomatic patients is not recommended. We retrospectively evaluated quality-adjusted survival. Included were fifty-seven recurrent breast cancer patients who died. Survival was partitioned into 3 health states by two different definitions: definition a) time with toxicities due to chemotherapy before progression (TOX1), time from the diagnosis of recurrence to progression without toxicities (TWiST1), and time from progression to death (REL1); definition b) time from the diagnosis of recurrence to death with toxicities (TOX2), without toxicities or hospitalization (TWiST2), and with hospitalization (REL2). Q-TWiST was calculated by multiplying the time in each health state by its utility (uTOX, uTWiST, and uREL). In threshold analyses, uTOX and uREL ranged from 0.0 to 1.0 whereas uTWiST was maintained at 1.0. We compared the patients with (n=32) and without (n=25) symptoms at the time of the diagnosis of recurrence. There was no difference in overall survival after primary surgery, although survival after the diagnosis of recurrence was significantly longer in the asymptomatic patients (p<0.01). Q-TWiST1 and Q-TWiST2 from the diagnosis of recurrence in the asymptomatic patients were significantly longer. Q-TWiST2 from primary surgery in the asymptomatic patients was significantly longer with some combinations of higher uTOX2 and lower uREL2. In conclusion, the asymptomatic detection of recurrence was associated with significantly longer quality-adjusted survival in comparison to symptomatic detection with some combinations of uTOX2 and uREL2. A prospective evaluation would clarify adequate follow-up methods after radical surgery for breast cancer.
BACKGROUND: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future.
METHODS: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients.
RESULTS: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects.
CONCLUSIONS: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.
Eligible participants will have 100-120 mL of peripheral blood or 80-100 mL of MNCs via apheresis collected and shipped to Children's National Hospital at ambient temperature. The sample will be used to manufacture the HST-NEET product. The autologous peripheral blood stem cell graft suitable for rescue following conditioning will be obtained either before or after the collection of blood to generate HST-NEETs. Pre-transplant conditioning will consist of BEAM; BCNU 300 mg/m\^2 on Day -6, Etoposide 100 mg/m\^2 BID and Ara-C 100 mg/m2 BID on Days -5, -4, -3 and -2 and Melphalan 140 mg/m2 on Day -1. ASCT on Day 0. If the mobilized graft contains greater than 5.0 x 106 CD34+ cells per kg, any additional cells should be cryopreserved as a "back-up" graft in the event of graft failure related to the HST-NEETs. Participants will receive one dose (2 x 107 cells/m\^2 ) of HST-NEETs between Days +3 to +7 based on the clinical condition of the participant. If this window is missed, the HST-NEETs may be administered up to Day +30 post-ASCT. Participants will be followed for at least one year after ASCT.
In total 14 patients are planned. Each participant participates in both experimental parts (100% O2 and ambient air). They are examined immediately after each HBO/ ambient air therapy. The allocation is randomized treated every three weeks with 2-hour therapies using pure O2 or indoor air. Randomized and double-blinded in a cross-over setting, one group of patients with type 2 diabetes is first treated with HBO therapy and the other group is first treated with room air. Here, an ambient pressure of 2.4 ATM is built up and then administered for respiration over a total of 90 minutes of pure O2. Patients are examined on two consecutive days for each part of the study.On the first day serum samples are taken and a sample is taken from the vastus lateralis muscle. A magnetic resonance spectroscopic examination (MRS) is performed on the patient subsequently. In this case, phosphorus metabolites (absolute quantification of ATP, Pi) and the ATP synthase flow rate (fATP) are determined non-invasively by means of 31P MRS and TG storage (HCL) by means of 1H-MRS.

On the next day of the trial patients are treated with HBO therapy or room air. A hyperinsulinemic-euglycemic clamp test (120-300 min) with administration of deuterated glucose (D- \[6,6-2H2\] glucose) (0-120 min) to measure muscular and hepatic insulin resistance will be performed after the end of HBO therapy or room air treatment performed. Indirect calorimetry determines energy consumption and substrate selection (lipid and glucose oxidation) in hyperinsulinaemia. After the end of the HBO therapy or room air treatment and 30 minutes after the start of the clamp test, a sample is taken from the vastus lateralis muscle again.
This will be a prospective, multicentre, open label, randomized, controlled trial. All consecutive infants diagnosed with IC, according to Rome III criteria, will be prospectively enrolled in a 12 months period by 3 different Pediatric Gastroenterology units: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"; Institute of Pediatrics of the University of Foggia; Endoscopy and Gastroenterology Unit, Department of Pediatrics, University of Messina.

After the enrollment, all children will be randomly assigned to receive Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122) (Group A), L reuteri DSM 17938 (108 CFU) (Group B) or Simethicone (Group C). Treatment will be given to subjects for 28 days. The study's primary outcome is defined as a reduction in the duration of average crying times, from baseline (day 0) to end of treatment (day 28). The secondary outcome measure is the number of participants who respond to treatment on days 28. Infants who experience a decrease in the daily average crying time of 50% from baseline will be considered as responders to the treatment. Parents will be instructed to complete a structured 28-day maternal diary, modified from Barr et al. in order to record the frequency of colic episodes and the daily crying and fussing time (in minutes), feeding schedule, stool frequency and characteristics, and any adverse events experienced (14). Follow-up visits will be conducted on study days 7, 14, 21 and 28 by the same study investigator. At that visit, diaries and unused study products will be returned.
BACKGROUND: Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children.
METHODS: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality.
DISCUSSION: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children.
TRIAL REGISTRATION: Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.
Active ingredients such as medicines are mixed with excipient and then kneaded together with binder and solvent such as alcohol or water to prepare a wetted paste. A mold is filled with this paste. Top and bottom surfaces of the paste within the mold are coated with powder such as lubricant in order to avoid possible sticking of the paste to the apparatus during a subsequent compression step. Then a compressive pressure is exerted on the surface of the paste. Thereafter, the tablet is taken from the mold. The molded tablet can contain water-soluble or fat-soluble medicine.
One time intravenous (IV) Infusion of up to 5 x 10\^6 allogeneic human mesenchymal stem cells per kilogram of body weight (hMSCs/kg). A dose escalation using the "3+3" design will be employed. The three doses are 1 x 10\^6, 3 x 10\^6, and 5 x 10\^6 hMSCs/kg. There is no placebo group. All study participants will receive stem cells.
Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.
Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.