anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Radiotherapy is widely used to treat various cancers. Its combination with immune checkpoint inhibitors is intensively studied preclinically and clinically. Although the first results were very encouraging, the number of patients who respond positively remains low, and the therapeutic benefit is often temporary. This review summarizes how radiation can stimulate an antitumor immune response and its combination with immunotherapy based on inhibiting immune checkpoints. We will provide an overview of radiotherapy parameters that should be better controlled to avoid downregulating the antitumor immune response. The low response rate of combining radiotherapy and immunotherapy could, at least in part, be caused by the stimulation of cancer cell invasion and metastasis development that occur at similar doses and number of radiation fractions. To end on a positive note, we explore how a targeted inhibition of the inflammatory cytokines induced by radiation with a cyclooxygenase-2 inhibitor could both support an antitumor immune response and block radiation-induced metastasis formation.
OBJECTIVE: The anticipatory prescribing of pro re nata medications and continuous subcutaneous infusion (CSCI) medication is essential for the timely management of symptomatic patients at the end of life. There is no evidence to support the safety or appropriateness of anticipatory CSCIs. In 2013, in response to safety concerns about end of life prescribing in the community, we designed an educational intervention to improve prescribing practices among non-specialist prescribers in this area.
METHODS HOW THE STUDY WAS PERFORMED: We performed a safety-focussed retrospective cohort analysis of end of life community prescriptions of anticipatory CSCIs over a 12-month period, 5 years after creating clinical guidelines and embedding a multiprofessional rolling education programme. Medications prescribed and administered for symptom control at the end of life are compared between specialist and non-specialist prescribers in terms of their adherence to best practice guidance.
RESULTS: Medications prescribed were not universally administered and more commonly not administered without specialist input. Prescriptions of higher doses of opioids and benzodiazepines beyond those recommended by guidance were significantly greater within the cohort of patients receiving specialist oversight. The prescription of a dose range did not result in excessive dose escalation. For patients not receiving specialist palliative care, median morphine and midazolam doses did not escalate at all once a CSCI was commenced. All midazolam administrations were safe.
CONCLUSIONS: The practice of anticipatory CSCI prescribing and administration can be safe in the community non-specialist setting when supported by clinical guidelines, specialist advice and ongoing multiprofessional education.
The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) had not been evaluated. The diagnostic impact of TBNA when the EBUS probe was adjacent to lesions remained to be determined.

Here we designed a randomized, prospective study to evaluate : (1) The diagnostic yield of EBUS-guided TBNA in PPLs; (2) The role of TBNA when EBUS probe was adjacent to the lesions. Lesions not visible by bronchoscopy were defined as PPLs (no findings of endobronchial lesions, extrinsic compression, submucosal infiltration, or orifice narrowing). The TBNA apparatus (Olympus NA-2C-1) was inserted through the working channel, and was advanced until it reached the target lesion which was localized by EBUS. Negative manual suction was applied with the 20 ml syringe. The specimens were then smeared on glass slides and immersed in 95% alcohol. At least 3 aspirates per lesion were obtained. Using simple randomization with random digit table, we randomly assigned patients to undergo EBUS-guided TBB and BW or EBUS-guided TBNA, TBB and BW.
The present invention relates to three decomposition products of native low class acyl gellan gum. The molecular weights of the three decomposition products are approximately 30,245 g/mole, 4,774 g/mole, and 718 g/mole, respectively. The decomposition products of native low class acyl gellan gum according to the present invention can b produced through an optional method for decreasing a molecular weight of low class acyl gellan gum. The method comprises homogenization, ultrasonic treatment, radiation, oxidation, and hydrolysis. The present invention also provides a method for containing a decomposition product of native low class acyl gellan gum which can be turned out to be advantageous in human health as a functional food additive in a food, a dietary supplement, or a beverage. The present invention also provides a use of a decomposition product of native low class acyl gellan gum to treat degenerative neuropathy and bone diseases.
At the same time of randomization code generation, blood samples for a baseline ROTEM® analysis will be drawn, and blood products will be ordered. Patients will be eligible to receive study drug (fibrinogen concentrate or 0.9% saline solution), according to the randomization code previously generated, only if FIBTEM® - A10 value is \<18 mm (corresponding to a MCF value of \<20 mm, that is a plasma fibrinogen level \<3 g/L).
Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).
BACKGROUND: Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated.
METHODS: The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays.
RESULTS: We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion.
CONCLUSION: Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients.
In two trials, vancomycin hydrochloride 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with C. difficile-associated diarrhea (CDAD). Enrolled subjects were 18 years of age or older and received no more than 48 hours of treatment with oral vancomycin hydrochloride or oral/intravenous metronidazole in the 5 days preceding enrollment. CDAD was defined as ≥3 loose or watery bowel movements within the 24 hours preceding enrollment, and the presence of either C. difficile toxin A or B, or pseudomembranes on endoscopy within the 72 hours preceding enrollment. Subjects with fulminant C. difficile disease, sepsis with hypotension, ileus, peritoneal signs or severe hepatic disease were excluded. 

Efficacy analyses were performed on the Full Analysis Set (FAS), which included randomized subjects who received at least one dose of vancomycin hydrochloride and had any post-dosing investigator evaluation data (N=259; 134 in Trial 1 and 125 in Trial 2). 

The demographic profile and baseline CDAD characteristics of enrolled subjects were similar in the two trials. Vancomycin hydrochloride-treated subjects had a median age of 67 years, were mainly white (93%), and male (52%). CDAD was classified as severe (defined as 10 or more unformed bowel movements per day or WBC ≥15000/mm3) in 25% of subjects, and 47% were previously treated for CDAD.

Efficacy was assessed by using clinical success, defined as diarrhea resolution and the absence of severe abdominal discomfort due to CDAD, on Day 10. An additional efficacy endpoint was the time to resolution of diarrhea, defined as the beginning of diarrhea resolution that was sustained through the end of the prescribed active treatment period. 

The results for clinical success for vancomycin hydrochloride-treated subjects in both trials are shown in Table 2.

The median time to resolution of diarrhea was 5 days and 4 days in Trial 1 and Trial 2, respectively. For subjects older than 65 years of age, the median time to resolution was 6 days and 4 days in Trial 1 and Trial 2, respectively. In subjects with diarrhea resolution at end-of-treatment with vancomycin hydrochloride, recurrence of CDAD during the following four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively. 

Restriction Endonuclease Analysis (REA) was used to identify C. difficile baseline isolates in the BI group. In Trial 1, the vancomycin hydrochloride-treated subjects were classified at baseline as follows 31 (23%) with BI strain, 69 (52%) with non-BI strain, and 34 (25%) with unknown strain. Clinical success rates were 87% for BI strain, 81% for non-BI strain, and 76% for unknown strain. In subjects with diarrhea resolution at end-of treatment with vancomycin hydrochloride, recurrence of CDAD during the following four weeks occurred in 7 of 26 subjects with BI strain, 12 of 56 subjects with non-BI strain, and 6 of 25 subjects with unknown strain.
This proposal aims to test the efficacy of a comprehensive approach to improving positive airway pressure (PAP) therapy acceptance and adherence and sleep quality among patients with SCI/D. The proposed study is very relevant to the mission of the VA in promoting optimal health for all Veterans, including those with disabilities. To this end, this study is a randomized controlled trial (RCT) comparing the efficacy of a combined sleep and PAP adherence program, called the "BEST" program (Best practices PAP + patient Education +ongoing Support and Training). The central aim of this proposal therefore is to test the efficacy between two PAP adherence programs. The study has two main aims. First, the investigators aim to test the efficacy of the educational program in improving adherence to PAP therapy for the first 6 months of use (with data available for some subjects for up to 12 months). Second, the investigators will evaluate the impact of the program on sleep quality and on three key areas of function: general functioning (using measures specific to SCI/D patients), respiratory functioning (via spirometry) and quality of life (assessed with measures appropriate for use with patients having limited mobility) over the 3-month intervention period. The investigators will also explore whether the intervention is more effective for some subgroups of patients than others. The proposed work is very relevant to VA's patient care mission, addressing a critical need for patients who suffer from disparity in access to high quality care because of their disabilities. The investigators anticipate that the investigators' work will yield significant new knowledge that improves the health and quality of life for Veterans living with SCI/D.
Brigatinib is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice.

At clinically achievable concentrations (≤500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.
BACKGROUND: Acute myocardial infarction (AMI) is indeed a significant cause of mortality and morbidity in individuals with coronary heart disease. Ferroptosis, an iron-dependent cell death, is characterized by the accumulation of intracellular lipid peroxides, which is implicated in cardiomyocyte injury. This study aims to identify biomarkers that are indicative of ferroptosis in the context of AMI, and to examine their potential roles in immune infiltration.
METHODS: Firstly, the GSE59867 dataset was used to identify differentially expressed ferroptosis-related genes (DE-FRGs) in AMI. We then performed gene ontology (GO) and functional enrichment analysis on these DE-FRGs. Secondly, we analyzed the GSE76591 dataset and used bioinformatic methods to build ceRNA networks. Thirdly, we identified hub genes in protein-protein interaction (PPI) network. After obtaining the key DE-FRGs through the junction of hub genes with ceRNA and least absolute shrinkage and selection operator (LASSO). ImmucellAI was applied to estimate the immune cell infiltration in each sample and examine the relationship between key DE-FRGs and 24 immunocyte subsets. The diagnostic performance of these genes was further evaluated using the receiver operating characteristic (ROC) curve analysis. Ultimately, we identified an immune-related ceRNA regulatory axis linked to ferroptosis in AMI.
RESULTS: Among 56 DE-FRGs identified in AMI, 41 of them were integrated into the construction of competitive endogenous RNA (ceRNA) networks. TLR4 and PIK3CA were identified as key DE-FRGs and PIK3CA was confirmed as a diagnostic biomarker for AMI. Moreover, CD4_native cells, nTreg cells, Th2 cells, Th17 cells, central-memory cells, effector-memory cells, and CD8_T cells had higher infiltrates in AMI samples compared to control samples. In contrast, exhausted cells, iTreg cells, and Tfh cells had lower infiltrates in AMI samples. Spearman analysis confirmed the correlation between 24 immune cells and PIK3CA/TLR4. Ultimately, we constructed an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA.
CONCLUSION: Our comprehensive analysis has identified PIK3CA as a robust and promising biomarker for this condition. Moreover, we have also identified an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA, which may play a key role in regulating ferroptosis during AMI progression.
A composition comprising (i) a HBcAg1-x, where x is a whole number from 100 to 160, a fragment of this antigen, a variant of this antigen or of the fragment of this antigen, (ii) an adjuvant comprising a saponin, and optionally (iii) a HBsAg, a fragment from this antigen, a variant of this antigen or of the fragment of this antigen, is new. A composition comprises (i) a HBcAg1-x, where x is a whole number from 100 to 160, a fragment of this antigen, a variant of this antigen or of the fragment of this antigen, (ii) an adjuvant comprising a saponin, and optionally (iii) a HBsAg, a fragment from this antigen, a variant of this antigen or of the fragment of this antigen, where the adjuvant comprises as saponin 50-90 wt.% of the fraction A obtained by the test method from Quillaja Saponaria Molina extract and 10-50 wt.% of the fraction C obtained by the test method from Quillaja Saponaria Molina extract, where the total amount of saponins of the fraction A and saponins of the fraction C is 100 wt.%; and the adjuvant comprises, besides the saponin, cholesterol, phosphatidylcholine and decanoyl-N-methylglucamide. An independent claim is a process for preparing the composition by providing the components (i) to (iii). ACTIVITY : Hepatotropic; Antiinflammatory; Virucide. No biological data given. MECHANISM OF ACTION : Vaccine.
Dementia is a chronic, progressive brain disease that may involve a number of symptoms, including memory loss and changes in personality, behavior, judgment, attention span, language and thought. The most common type of dementia is Alzheimer's disease. Over time, patients with Alzheimer's disease may lose ability to perform daily tasks related to personal care (for example bathing, dressing, eating) and may be unable to handle money or travel to familiar places. Several small clinical trials have shown galantamine to be safe and effective in treating the symptoms associated with Alzheimer's disease. Doses studied have ranged from 15 - 60 mg/day, with galantamine administered two or three times daily. Additional information is needed to determine the optimal dose regimen for galantamine in the treatment of Alzheimer's' disease. This multicenter, double-blind, placebo-controlled (neither the patient nor the study doctor know the dose of galantamine being given) study evaluates the safety and effectiveness of two doses of galantamine, each given twice daily, in the treatment of patients with Alzheimer's disease. All patients initially receive placebo for a 1-month period and then receive one of two doses of galantamine (beginning at 4 mg twice daily and gradually increasing to 12 or 16 mg twice daily) or placebo for 6 months. The primary measures of effectiveness include the change from baseline to the end of treatment in the ADAS-cog/11 score (Alzheimer's Disease Assessment Scale: sum of 11 cognitive items) and the CIBIC-plus score (Clinician's Interview Based Impression of Change - Plus Caregiver Input). Additional measures of effectiveness assessed at the end of the treatment include the ADAS-cog/13 score (Alzheimer's Disease Assessment Scale: sum of 13 cognitive items) and the Disability Assessment for Dementia (DAD) score. Safety evaluations (incidence of adverse events, electrocardiograms (ECGs), physical examinations, laboratory tests) are performed throughout the study. Caregiver quality of life (Psychological General Well Being Index, \[PGWB\]) and health/social care resource utilization (physician and other health care professional visits, use of social services, etc.) are also assessed throughout the study by questionnaires answered by the caregivers. Blood samples are taken throughout the study to determine the concentration of drug in the blood. Patients may also participate in an optional portion of the study in which their genetic material is analyzed to see if contains something that would affect the way galantamine is used by their bodies. The study hypothesis is that galantamine administered in either dose is effective in the treatment of Alzheimer's disease as compared with placebo, and is well tolerated. This study will be conducted internationally. A companion study of exact design will be conducted in the United States. Galantamine tablets (or placebo), taken orally twice daily for 6 months beginning with 4 mg twice daily and gradually increasing to 12 or 16 mg twice daily.
The intervention group will receive 12 weekly 90-minute combined cognition interventions in a group. The first half of each session will be cognitive training which focus on teaching various cognitive strategies and their applications to enhance the attention, memory, processing speed, and executive functions. The second half of the session will apply rehabilitation intervention with various compensatory strategies. Investigators will use group discussion to discuss everyday situations with memory problem and specific strategies (internal and external) related to real-life situations. Investigators will also include one individual session in the 12 group sessions.
Asthma is a serious global health problem affecting 300 million persons around the world. Mast cells (MCs) play a major role in airway hyperresponsiveness (AHR) and inflammation in asthma, their exact effector mechanisms remain unclear. Here, we aim to investigate the inhibitory effect of Bergapten (BER) on MRGPRX2-mediated MCs activation through asthma model. Mouse model of asthma was established to examine the anti-asthmatic effects of BER. Calcium (Ca2+) influx, β-hexosaminidase and histamine release were used to assess MCs degranulation in vitro. RNA-Seq technique was conducted to study the gene expression profile. RT-PCR and Western Blotting were performed to examine targeting molecules expression. BER inhibited AHR, inflammation, mucous secretion, collagen deposition and lung MCs activation in asthma model. BER dramatically reduced levels of IL4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), as well as inflammatory cells. BER also reduced serum IgE levels. Pretreatment MCs with BER inhibited substance P (SP)-induced Ca2+ influx, degranulation and cytokines release from MCs. BER also reduced the phosphorylation levels of PKC, PLC, IP3R, AKT and ERK, which were induced by SP. Furthermore, RNA-seq analysis showed that SP up-regulated 68 genes in MCs, while were reversed by BER. Among these 68 genes, SP up-regulated NR4A1 expression, and this effect was inhibited by BER. Meanwhile, knockdown of NR4A1 significantly attenuated SP-induced MCs degranulation. In conclusion, NR4A1 plays a major role in MRGPRX2-mediated MCs activation, BER inhibited AHR and inflammation in asthmatic model by inhibiting MCs activation through MRGPRX2-NR4A1 pathway.
Participants will limit their eating (all food and caloric beverages) to an eating window of 10 hours per day for 4 weeks. The eating window must end by 8pm. Water and non-caloric beverages are allowed outside of the eating window. No other changes are required to the types or total amount of food eaten.