anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.
METHODS: This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.
FINDINGS: Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.
INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9.
FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.
Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the BEIZRAY infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with BEIZRAY [see Contraindications ( 4)] . 

  
Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of BEIZRAY therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a BEIZRAY infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of BEIZRAY. [see Dosage and Administration ( 2.6)] .
Nilotinib is a second-generation tyrosine kinase inhibitor with improved efficacy compared to imatinib. However, there are still many patients for whom the therapeutic response is inadequate, or toxicity is limiting the treatment. Serum concentration of nilotinib was shown to affect time to response and progression in previous studies. Therefore, the investigators hypothesized that the optimal plasma level of nilotinib that is sufficient to achieve adequate clinical response while not generating major adverse events could be elucidated by the analysis of combined clinical and pharmacokinetic data.

ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily), in adult patients diagnosed as Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in chronic phase (CML-CP). Plasma samples are collected every three months, for up to 12 months, to determine plasma nilotinib concentrations (PNCs). The primary endpoint is the cumulative rate of molecular response 4.5 (MR4.5; BCR-ABL1IS ≤ 0.0032%) by 24 months. Secondary endpoints include the cumulative rates of MR3 (BCR-ABLIS ≤ 0.1%) and MR4 (BCR-ABLIS ≤ 0.01%) by 12 and 24 months; time to MR3, MR4, and MR4.5; progression-free survival (PFS); overall survival (OS). Correlations between PNCs and clinical outcomes are also analyzed.
This group will receive 4 hours of small-group and hands-on sessions on colonoscopy theory from an expert endoscopist. The core curriculum is designed on the basis of the American Society for Gastrointestinal Endoscopy colonoscopy curriculum and an endoscopic training textbook. This curriculum has been shown to be effective when compared to self-regulated learning on the simulator. The sessions will be interlaced with eight hours of expert-assisted instruction on both the low-fidelity simulator (1 hour) and on the high-fidelity VR simulator (7 hours). Six modules of increasing difficulty in colonoscopy and polypectomy will be taught with feedback from an expert endoscopist. The expert will demonstrate techniques, answer questions and provide feedback on global performance. Feedback, in the form of performance metrics, will be provided by the simulator upon completion/failure of each module.
Each subject will have routine clinical care imaging obtained and 4 standard mammogram views (RMLO, RCC, LMLO, LCC) using CR mammography. If routine mammograms were obtained on a day previous to enrollment in the study, those images (4 views; 2 views for mastectomy patients) will not be repeated for this study; only the CR images will be obtained.
Elderly individuals were divided into 5 groups according to the stages of change in the TTM scale. According to the change phase, those in the non-thinking phase are at 10:00 on Mondays, Wednesdays and Fridays, those in the thinking phase are at 13:00 on Mondays, Wednesdays and Fridays, and those in the preparatory phase are at 15:00 on Mondays, Wednesdays and Fridays of the week. They were asked to come to the seminar hall at 00:00. It was explained that a training video about physical activity would be watched. Those in the preparation phase were asked to come to the activity hall at 10:00 on Tuesdays, Thursdays and Saturdays of the week, and at 14:00 on Tuesdays, Thursdays and Saturdays of the week, while wearing their comfortable clothes. It was said that a training and motivational video about physical activity would be watched and the exercises would be done under the supervision of the researcher with the "show-and-make technique".
There was no evidence of carcinogenicity when candesartan cilexetil was orally administered to mice and rats for up to 104 weeks at doses up to 100 and 1000 mg/kg/day, respectively. Rats received the drug by gavage, whereas mice received the drug by dietary administration. These (maximally-tolerated) doses of candesartan cilexetil provided systemic exposures to candesartan (AUCs) that were, in mice, approximately 7 times and, in rats, more than 70 times the exposure in man at the maximum recommended daily human dose (32 mg).

Candesartan and its O-deethyl metabolite tested positive for genotoxicity in the in vitro Chinese hamster lung (CHL) chromosomal aberration assay. Neither compound tested positive in the Ames microbial mutagenesis assay or the in vitro mouse lymphoma cell assay. Candesartan (but not its O-deethyl metabolite) was also evaluated in vivo in the mouse micronucleus test and in vitro in the Chinese hamster ovary (CHO) gene mutation assay, in both cases with negative results. Candesartan cilexetil was evaluated in the Ames test, the in vitro mouse lymphoma cell and rat hepatocyte unscheduled DNA synthesis assays and the in vivo mouse micronucleus test, in each case with negative results. Candesartan cilexetil was not evaluated in the CHL chromosomal aberration or CHO gene mutation assay.

Fertility and reproductive performance were not affected in studies with male and female rats given oral doses of up to 300 mg/kg/day (83 times the maximum daily human dose of 32 mg on a body surface area basis).
Introduced here are containers designed to promote compliance with regimens for administering the medications stored therein. These containers have various features that allow them to be more easily managed by the individuals to whom the medications were prescribed. Some features improve the ease with which containers communicate with individuals. These features may enable information to be more easily input by individuals and/or output for individuals in a comprehensible manner. Other features improve the mechanical or electrical durability of containers. Such features may enable the containers to be used by individuals over the course of several days, weeks, or months without worrying about structural damage or loss of power.
BACKGROUND AND AIMS: Whole grain consumption is widely recognized as a vital component of a balanced diet. Dietary fiber has been well-documented to play a crucial role in these health benefits attributed to whole grain intake. However, population-based evidence directly linking whole grain consumption to anti-inflammatory effects, especially in the context of immune-mediated inflammation, remains limited. We hypothesized that whole grain consumption promotes health by modulating immune-mediated inflammation.
METHODS AND RESULTS: This study was designed as a real-world, population-based randomized controlled trial. We compared the effects of whole grain versus refined grain consumption on immune-mediated inflammation through staple food substitution, while participants maintained their usual dietary practices. The results demonstrated that whole grain consumption significantly reduced circulating levels of pro-inflammatory cytokines IL-22 and IL-23 compared to refined grain consumption. These reductions were associated with optimized short-chain fatty acid profiles and changes in CD4+ T cell subset distributions.
CONCLUSIONS: The findings suggest that the anti-inflammatory effects of whole grain consumption in middle-aged and elderly populations are mediated by targeting specific CD4+ T cell subsets, in addition to modulating both upstream short-chain fatty acid composition and downstream expression of the pro-inflammatory cytokines IL-22 and IL-23.
The present invention is oral clodronate preparation and its liposome with high absorption, high bioavailability and high stability and its preparation. The preparation is prepared into common orally taken tablet, dispsersive tablet, coated tablet, sublingual tablet, oral cavity disintegrated tablet, etc. The liposome or liposome precursor is prepared with clodronate and phosphatide, cholesterol, supporting agent and other supplementary material. It has phosphatide/medicine weight ratio of 0.1-40, and is prepared through ethanol injecting process, film dispersion process, inverse evaporation process, extruding process or mechanical process. The supporting agent may be sorbitol, mannitol, cane sugar, etc. and has ratio to phosphatide of 0.01-400. The present invention is suitable for treating cancer caused osteolytic bone metastasis, osteoporosis and hypercalcinemia.
Participants prescribed 150 minutes/week of moderate to vigorous exercise. The exercises include cycling, walking/jogging, yoga/Pilates, and cross-training, and each week another exercise will be added to the list of options for participants. Participants may choose from the list of exercise. They do not have to do them all, and they can do as much or little (none) of whatever they choose.
A method and system in a computing environment for preventing atypical clinical events associated with clinical agent administration to a person is provided. Clinical agent information is received. A data structure is accessed to determine if genetic findings are known to be associated with atypical events for the clinical agent. An electronic medical record is accessed to determine if a person has a stored genetic test result value for the genetic finding. Upon determining that the person does not have a stored genetic test result value, a population genetics inference based solely on demographic information is calculated indicating a likelihood the person has the genetic finding. An output is generated that includes a risk associated with atypical events for the clinical agent; the risk is based solely on the population genetics inference.
OBJECTIVES: I. Determine the toxicity of dimethylxanthenone acetic acid (DMXAA) in patients with solid tumors. II. Establish a maximum tolerated dose for this drug in these patients. III. Determine the pharmacokinetics of DMXAA in these patients. IV. Determine the effect of this regimen on coagulation parameters, TNF and other cytokine production, nitric oxide, and serotonin production in these patients. V. Assess the efficacy of this drug in this patient population. VI. Determine the effect of this drug on tumor vasculature by evaluating any changes apparent on MRI scans in these patients.

OUTLINE: This is a dose escalation, multicenter study. Patients receive dimethylxanthenone acetic acid (DMXAA) IV over 20 minutes once weekly for 6 weeks, followed by 2 weeks of rest. An additional course of therapy may be administered in the absence of unacceptable toxicity or disease progression. Cohorts of 3 patients receive escalated doses of DMXAA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose limiting toxicity.

PROJECTED ACCRUAL: A minimum of 3 patients will be accrued to each dose level used to determine the maximum tolerated dose.
The present invention provides a medicament for the treatment or prevention of radiation-induced organ damage. In particular to application of amniotic fluid or a pharmaceutical composition containing the amniotic fluid in preparing medicines for preventing or treating radioactive organ injury. The amniotic fluid is derived from an egg with an embryo age of 7-9 days, or from other fowl eggs except for a chicken whose development period corresponds to that of the embryo-age egg. The radioactive source is X-rays or gamma rays, space rays, nuclear radiation and the like. The radioactive injury is systemic organ injury of the organism, and the general manifestations include, but are not limited to, increased mortality, weight loss, reduced food intake, reduced exercise capacity and the like. The internal organ injury includes, but is not limited to, heart, liver, spleen, lung, kidney and other main internal organs with reduced quality and damaged structure, serious spleen oxidative stress injury and DNA injury, and the resulting imbalance of spleen lymphocyte proportion and hematopoietic function decline, etc.
OBJECTIVE: To analyze the clinical efficacy and safety of fractional microneedle radiofrequency (FMR) for facial atrophic acne scars in a real-world setting.
METHODS: The clinical data of patients with atrophic acne scars who had received FMR therapy from February 2018 to August 2022 were retrospectively analyzed. The improvement of atrophic acne scars was assessed using the ECCA Grading Scale (échelle d'évaluation clinique des cicatrices d'acné), Global Aesthetic Improvement Scale (GAIS), and modified Manchester Scar Scale (mMSS). Adverse reactions during FMR treatment were also recorded. Univariate and multivariate logistic regression analyses were performed to evaluate the efficacy and safety of FMR for atrophic acne scars.
RESULTS: A total of 126 patients with facial atrophic acne scars were included. A total of 590 FMR treatment sessions were accomplished, with each of 82 patients receiving 4 or more treatment sessions, and 1 receiving a maximum of 14 sessions. All patients showed improvement in symptoms after FMR treatment, with moderate to significant improvement (ECCA score reduction of 26%-100%) in 92 (73.0%) patients. As the number of treatment sessions increased, the ECCA score gradually decreased from an average of 85.6 before to 35.0 after FMR. The average scores for distortion, color, and visual analogue scale (VAS) of mMSS all showed certain reductions. The change in GAIS score indicated improvement after treatment, with minimal improvement in 16 patients (12.7%), good improvement in 57 patients (45.2%), significant improvement in 45 patients (35.7%), and optimal improvement in 8 patients (6.4%). The univariate and multivariate logistic regression analyses revealed that the long pulse width and the number of FMR treatment sessions were positively associated with clinical efficacy. Compared to the short pulse-width group (200 ms), the longer pulse-width group (300 ms) (odds ratio [OR] = 8.3, p = 0.003) and the even longer pulse-width group (400-500 ms) (OR = 52.6, p < 0.001) demonstrated stronger efficacies. Patients who received more than three treatment sessions had better outcomes compared to those who received three or fewer treatment sessions (OR = 4.0, p = 0.036). All patients experienced posttreatment transient erythema, but no crusting, infection, or blister. Six cases developed grid-like erythema around 1 month posttreatment and one case experienced hyperpigmentation, both of which resolved within 1-3 months after appropriate management.
CONCLUSION: FMR is a safe and effective treatment modality for improving facial atrophic acne scars, and the number of FMR treatment sessions and pulse width are associated with clinical efficacy.
Hypotension and bradycardia have been reported following propranolol overdose and should be treated appropriately. Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a propranolol overdose. Glucagon should be administered as 50-150 mcg/kg intravenously followed by continuous drip of 1-5 mg/hour for positive chronotropic effect. Isoproterenol, dopamine or phosphodiesterase inhibitors may also be useful. Epinephrine, however, may provoke uncontrolled hypertension. Bradycardia can be treated with atropine or isoproterenol. Serious bradycardia may require temporary cardiac pacing.

The electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance must be monitored. Isoproterenol and aminophylline may be used for bronchospasm.   
  
To report SUSPECTED ADVERSE REACTIONS contact AvKARE, Inc. at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
No intervention will be made to the control group, only the data will be collected at the same time as the study group. After all data are collected (after the 12th week), the training content will be explained to the nurses in the control group and the MIND-BE program will be started for them as well. In this way, both groups will benefit from this program.
Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation. ZFHX3 was found to interact with the chromatin remodeling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex, suggesting a function in chromatin remodeling and mRNA processing. Furthermore, ChIP-seq for ZFHX3 revealed that it predominantly binds promoters of genes involved in nervous system development. We conclude that loss-of-function variants in ZFHX3 are a cause of syndromic ID associating with a specific DNA methylation profile.
BACKGROUND: Ubiquitin-specific protease 7 (USP7) has been found to be associated with motor function recovery after spinal cord injury (SCI). Therefore, its role and mechanism in SCI process need further exploration.
METHODS: SCI rat models were established via performing laminectomy at the T9-T11 spinal vertebrae and cutting spinal cord tissues. SCI cell models were constructed by inducing PC12 cells with lipopolysaccharide (LPS). The protein levels of USP7, nuclear respiratory factor 1 (NRF1), Krüppel-like factor 7 (KLF7) and apoptosis-related markers were detected by western blot. Cell viability and apoptosis were tested by cell counting kit-8 assay and flow cytometry. The contents of inflammatory factors were examined using ELISA. The interaction between NRF1 and USP7 or KLF7 was analyzed by co-immunoprecipitation assay, chromatin immunoprecipitation assay and dual-luciferase reporter assay, respectively.
RESULTS: USP7 was downregulated in SCI rat models and LPS-induced PC12 cells. Overexpressed USP7 promoted viability, while repressed apoptosis and inflammation in LPS-induced PC12 cells. USP7 could stabilize NRF1 protein expression via deubiquitination, and NRF1 knockdown reversed the protective effect of USP7 against LPS-induced PC12 cell injury. NRF1 is bound to KLF7 promoter to enhance its transcription. NRF1 overexpression inhibited LPS-induced PC12 cell inflammation and apoptosis via increasing KLF7 expression.
CONCLUSION: USP7 alleviated inflammation and apoptosis in LPS-induced PC12 cells via NRF1/KLF7 axis, indicating that targeting of USP7/NRF1/KLF7 axis might be a promising treatment strategy for SCI.