anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Myocardial damage is a critical complication and a significant contributor to mortality in sepsis. MicroRNAs (miRNAs) have emerged as key players in sepsis pathogenesis. In this study, we explore the effect and mechanisms of miR-29b-1-5p on sepsis-induced myocardial damage. Sepsis-associated Gene Expression Omnibus datasets (GSE72380 and GSE29914) are examined for differential miRNAs. The mouse sepsis-induced cardiac injury was established by Lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). LPS-treated HL-1 mouse cardiomyocytes simulate myocardial injury in vitro. miR-29b-1-5p is co-upregulated in both datasets and in cardiac tissue from sepsis mouse and HL-1 cell models. miR-29b-1-5p expression downregulation was achieved by antagomir transduction and confirmed by real-time quantitative reverse transcription PCR. Survival analysis and echocardiography examination show that miR-29b-1-5p inhibition improves mice survival cardiac function in LPS- and CLP-induced sepsis mice. Hematoxylin and eosin and Masson's trichrome staining and Immunohistochemistry analysis of mouse myocardial α-smooth muscle actin show that miR-29b-1-5p inhibition reduces myocardial tissue injury and fibrosis. The inflammatory cytokines and cardiac troponin I (cTnI) levels in mouse serum and HL-1 cells are also decreased by miR-29b-1-5p inhibition, as revealed by enzyme-linked immunosorbent assay. The expressions of autophagy-lysosomal pathway-related and apoptosis-related proteins in the mouse cardiac tissues and HL-1 cells are evaluated by western blot analysis. The sepsis-induced activation of the autophagy-lysosomal pathway and apoptosis are also reversed by miR-29b-1-5p antagomir. MTT and flow cytometry measurement further confirm the protective role of miR-29b-1-5p antagomir in HL-1 cells by increasing cell viability and suppressing cell apoptosis. Metascape functionally enriches TargetScan-predicted miR-29b-1-5p target genes. TargetScan prediction and dual luciferase assay validate the targeting relationship between miR-29b-1-5p and telomeric repeat-binding factor 2 (TERF2). The expression and function of TERF2 in HL-1 cells and mice are also evaluated. MiR-29b-1-5p negatively regulates the target gene TERF2. TERF2 knockdown partly restores miR-29b-1-5p antagomir function in LPS-stimulated HL-1 cells. In summary, miR-29b-1-5p targetedly inhibits TERF2, thereby enhancing sepsis-induced myocardial injury.
Patients are exposed to infectious agents regularly, regardless of their immunologic status. Traditionally clinicians have decided to institute prophylaxis based on epidemiologic factors, skin test (i.e. PPD), or immunologic parameters. A quantitative and specific method that is non-invasive, such as quantitative PCR, would be desirable to more precisely define those who would benefit from prophylaxis. Similarly, when patients develop disease and are being treated, quantitative, non-invasive techniques are needed to assess response to therapy. This project is designed to develop and test quantitative tests using blood, urine, or sputum samples.
Preeclampsia affects approximately 5-8% of pregnancies in the United States with approximately 10% occurring before 34 weeks gestation. The diagnosis of preeclampsia is determined by the presence of hypertension with proteinuria after 20 weeks gestation. The gold standard for measuring proteinuria is a 24-h urine collection for total protein. In the non-pregnant patient, a random urinary protein-to-creatinine ratio has been shown to be a reliable indicator of significant proteinuria. The reliability of this test remains unclear in the pregnant population. Because there are relatively few studies in the pregnant population and many of these studies were poorly designed, limited by sample size, or confounded by other variables, further research in this area is still necessary. The purpose of this study is to determine if there are alternative diagnostic tools for the quantification of total protein excretion in 24-hours to aid in the diagnosis of preeclampsia that can be performed more quickly and efficiently than the gold standard 24-hour urine collection. We intend to perform a large prospective study looking at the predictability of the random urine protein-to-creatinine ratio compared to the gold standard 24-h urine protein collection. Furthermore, we plan to investigate whether analysis of proteinuria at shorter time intervals (4 and 8 hours) within the overall 24-h collection period is predictive of the 24-h sample. Lastly, we plan to determine whether a combination of the random test with a shorter collection interval is comparable to the 24-h collection. The goal would be to make the diagnosis of preeclampsia in a more timely fashion to aid in the prevention of maternal and neonatal morbidity and mortality including eclampsia, HELLP syndrome, acute renal failure, pulmonary edema, DIC, IUGR, IUFD, intracranial bleeding and stroke, Additionally, an earlier diagnosis could also impact patient care by reducing hospital stay, nursing demands, and eliminating the need for cumbersome and likely inaccurate patient 24-h home collections.
An emulsion comprises an oil phase dispersed in an aq. phase using a silicone emulsifier. The oil phase contains at least 50 wt.% silicone oil. The novelty is that the aq. phase contains at least one polyol (I) in an amt. providing the emulsion with a water activity of 0.85 or less (pref. 0.7 or less). Also claimed is a compsn. (C) comprising at least one water-sensitive topical active ingredient (A) and the emulsion.
Two minutes before the painful procedure and at the moment of the procedure, the infant will be given 24% sucrose by mouth. The volume is determined by body weight and is not important in terms of efficacy, it is the percentage of sweetness that is important.
Weight loss was a common adverse reaction in roflumilast clinical trials and was reported in 7.5% (331) of patients treated with roflumilast 500 mcg once daily compared to 2.1% (89) treated with placebo [see Adverse Reactions (6.1)]. In addition to being reported as adverse reactions, weight was prospectively assessed in two placebo-controlled clinical trials of one year duration. In these studies, 20% of patients receiving roflumilast experienced moderate weight loss (defined as between 5 to 10% of body weight) compared to 7% of patients who received placebo. In addition, 7% of patients who received roflumilast compared to 2% of patients receiving placebo experienced severe (>10% body weight) weight loss. During follow-up after treatment discontinuation, the majority of patients with weight loss regained some of the weight they had lost while receiving roflumilast. Patients treated with roflumilast should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, weight loss should be evaluated, and discontinuation of roflumilast should be considered.
Periodontitis develops due to subgingival infection with specific microbial pathogen from dental plaque. The bacteria can activate immunoinflammatory mechanisms within the local periodontal tissues that lead to destruction of collagen and alveolar bone. Bacterial antigens can release from the supra and subgingival dental plaque on the tooth surface as well as from bacteria attached to mucosal surfaces. The sulcular epithelium served as a physical barrier to the insult of the bacteria, the presence of Langerhans cells is also responsible for communication with the immune system. Dendritic cells (DCs), the most effective antigen-presenting cells, contact and process the antigens. Signals from pathogen induce dendritic cells to maturation. Mature DCs rapidly increase surface expression and stability of MHC class I and class II-peptide complexes, upregulate the surface expression of adhesion and co-stimulatory molecules (CD40, CD54, CD80, and CD86) and secrete proinflammatory cytokines such as IL-1, IL-6, IL-12........ then they migrate to lymphoid organs, where they regulate T cell immune response. Human gingiva contains Langerhans and connective tissue dendritic cells. Immature dendritic cells appeared to be limited to the epithelium, whereas mature dendritic cells were restricted to the connective tissue. Studies on cytokines have led to controversy about the the different T cell subsets associated with the progression of periodontitis. Seymour proposed that susceptibility to periodontal disease progression involve a predominantly Th2 response while Ebersole speculated that Th2 cells providing protective function. Progression of periodontitis is also associated with the presence of gram-negative anaerobic microorganism such as Porphyromonas gingivalis, Bacteroides forsythus. Different bacteria and their LPS can elicit strikingly different response. It is possible that a given pathogen may produce different maturation signals by selectively activating a particular DC subset to induce a given type of immune response. In this study, we observed the profiles and amounts of cytokine production of DCs stimulated with P. gingivalis and T. forsythensis compared with E. coli, to see whether the periodontal pathogens may induce different response of dendritic cells in the innate immunity.
Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.
The mechanisms of epileptogenesis after brain injury, ischemic stroke, or brain tumors have been extensively studied. As a result, many effective antiseizure drugs have been developed. However, there are still many patients who are resistant to therapy. The molecular and genetic bases regarding such drug-resistant seizures have been poorly elucidated. In many cases, heavy seizures are instigated by brain development malformations and often caused by gene mutations. Such malformations can be demonstrated in mouse models by generating mutant strains. One of the most potent mutagens is ENU (N-ethyl-N-nitrosourea). In the present study, we describe three novel mutant strains generated by ENU-directed mutagenesis. Two of these strains present a very strong epileptic phenotype triggered by audiogenic stimuli (G9-1 and S5-1 strains). The third mouse strain is characterized by behavioral disorders and hyperexcitation of neuronal networks. We identified changes in the expression of those genes encoding neurotransmission proteins in the cerebral cortexes of these mice. It turned out that the G9-1 strain demonstrated the strongest disruptions in the expression of those genes encoding plasma membrane channels, excitatory glutamate receptors, and protein kinases. On the other hand, the number of GABAergic neurons was also affected by the mutation. All three lines are characterized by increased anxiety, excitability, and suppressed motor and orientational-exploratory activities. On the other hand, the strains with an epileptic phenotype-G9-1 and S5-1ave reduced learning ability, and the A9-2 mice line retains high learning ability.
Prophylactic norepinephrine infusion is started at the beginning of anesthetic induction and maintained throughout surgery. The target is to maintain systolic blood pressure at 110 mmHg or higher during surgery.
Patients have access to a website where they can self-report smoking status, add virtual supporters, and submit journal entries. Patients receive incentives for completing these activities and for utilizing counseling services at the clinic. At the 2 mo. mark, these participants come to the clinic for a biochemical verification of their smoking status. Their rewards are contingent on successfully passing this verification test. They are also asked to return to the clinic 6 and 12 mos. after enrollment to complete the smoking tests and are compensated for these 2 visits.
Cancer is the leading cause of death in women in the United States (US). Chinese Americans are the largest ethnic group among Asian Americans. Although the incidence of breast cancer, the most common cancer in women, has decreased among other U.S racial groups over the last 15 years, Chinese American women in California have experienced a significant increase of incidence of 1.1% from 1998 to 2013. Studies have found that assimilation stress and obesity are associated with increased risk for breast cancer in Chinese American women. There are no existing interventions targeted at breast cancer prevention among premenopausal mothers with abdominal obesity. Interventions tailored to an individual's cultural, lifestyle and social support system are needed to reduce obesity and breast cancer risk. A smartphone-based intervention provides a promising platform for obesity and cancer prevention. The overall goal of this project is to test the feasibility of an obesity and breast cancer prevention intervention among Chinese American women in San Francisco. The investigators will adapt the Healthy Mothers Healthy Children: Technology-Based Intervention to Prevent Obesity to reduce obesity and breast cancer risk in premenopausal women with abdominal obesity who have dependent children in San Francisco. The proposed intervention ("Smartphone-Based Cancer and Obesity Prevention Program for Chinese Women: SCOPP-CW) includes 12 weekly educational modules and six bi-weekly tailored messages delivered via WeChat, a popular private communication app used by Chinese and Chinese Americans. The investigators propose to conduct a pilot randomized control study (RCT) to assess the short-term efficacy of SCOPP-CW on abdominal obesity, breast cancer knowledge and attitudes, weight-related behaviors (food intake and physical activity), and metabolic risk (blood pressure, lipid profile, hemoglobin A1c), which are associated with breast cancer. Thus the investigators propose the following aims: (1) Aim 1: To estimate the preliminary efficacy of the SCOPP-CW intervention on the primary outcomes (i.e. waist circumference and breast cancer knowledge and attitudes) and secondary outcomes (i.e. body mass index, self-efficacy, food intake, physical activity at baseline, 3 months, and 6 months, and metabolic risk \[blood pressure, hemoglobin A1C, and lipid panel\]) at baseline and 6 months.

Aim 2: To assess feasibility by understanding participants' acceptance, barriers to adherence and recommendations for intervention using focus group interviews. The investigators anticipate that this intervention will have a significant impact on breast cancer prevention. The investigators plan to use the proposed pilot study's findings to conduct a larger scale randomized trial (R01) to test the long-term efficacy of the intervention.
The proposed bCBT treatment for anxiety was specifically designed for use within VA PCMHI settings and uses a patient-centered approach to increase engagement while addressing the mental health needs of anxious Veterans. Emphasis was placed on maximizing intervention potency and minimizing intensity and duration to improve implementation value and alignment with VA PCMHI requirements. The intervention directly addresses challenges to delivery of CBT providing 1) a brief, practical model of care to address multiple anxiety conditions consistent with the PCMHI model (e.g. 4-6 sessions; measurement-based care), and 2) a clinically potent intervention that includes exposure-based skills.
BACKGROUND: During gynecological laparoscopic surgery, pneumoperitoneum and the Trendelenburg position (TP) can lead to increased intracranial pressure (ICP). However, it remains unclear whether perioperative fluid therapy impacts ICP. The purpose of this research was to evaluate the impact of restrictive fluid (RF) therapy versus conventional fluid (CF) therapy on ICP in gynecological laparoscopic surgery patients by measuring the ratio of the optic nerve sheath diameter (ONSD) to the eyeball transverse diameter (ETD) using ultrasound.
METHODS: Sixty-four patients who were scheduled for laparoscopic gynecological surgery were randomly assigned to the CF group or the RF group. The main outcomes were differences in the ONSD/ETD ratios between the groups at predetermined time points. The secondary outcomes were intraoperative circulatory parameters (including mean arterial pressure, heart rate, and urine volume changes) and postoperative recovery indicators (including extubation time, length of post-anaesthesia care unit stay, postoperative complications, and length of hospital stay).
RESULTS: There were no statistically significant differences in the ONSD/ETD ratio and the ONSD over time between the two groups (all p > 0.05). From T2 to T4, the ONSD/ETD ratio and the ONSD in both groups were higher than T1 (all p < 0.001). From T1 to T2, the ONSD/ETD ratio in both groups increased by 14.3%. However, the extubation time in the RF group was shorter than in the CF group [median difference (95% CI) -11(-21 to -2) min, p = 0.027]. There were no differences in the other secondary outcomes.
CONCLUSION: In patients undergoing laparoscopic gynecological surgery, RF did not significantly lower the ONSD/ETD ratio but did shorten the tracheal extubation time, when compared to CF.
TRIAL REGISTRATION: ChiCTR2300079284. Registered on December 29, 2023.
Healthy dieters will undergo a single-visit neuroimaging study where they will first complete demographic and self-report measures followed by a self-control decision task in an fMRI scanner. Prior to scanning, participants will be assigned to the physiological non-stress group and complete the corresponding stress task. For the physiological non-stress group, participants will continuously submerge their hand and forearm in warm water for 3 minutes. After the scan, participants will wait for 1 hour in an adjacent study room where they will play out one trial of the decision-making task completed in the scanner.
All subjects will receive treatment A followed by treatment B. Treatment A consists of a single oral dose (1 mg) of riociguat (Adempas) on Day 1. Treatment B consists of a loading oral dose of 30 mg macitentan (Opsumit) (3 tablets of 10 mg) on Day 5, then 10 mg of macitentan once daily from Day 6 to Day 15, with a concomitant administration of riociguat (1 mg) on Day 10.
The efficacy of CYRAMZA was evaluated in RAISE (NCT01183780), a multinational, randomized, double-blind study in patients with mCRC, who had disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Patients in RAISE were required to have ECOG PS 0 or 1 and to have disease progression within 6 months of the last dose of first-line therapy. Patients were randomized (1:1) to receive either CYRAMZA at 8 mg/kg as an intravenous infusion or placebo, in combination with FOLFIRI: irinotecan 180 mg/m2 administered intravenously over 90 minutes and folinic acid 400 mg/m2 administered intravenously simultaneously over 120 minutes; followed by fluorouracil 400 mg/m2 intravenous bolus over 2 to 4 minutes; followed by fluorouracil 2400 mg/m2 administered intravenously by continuous infusion over 46 to 48 hours. Treatment cycles on both arms were repeated every 2 weeks. Patients who discontinued one or more components of treatment because of an adverse reaction were permitted to continue therapy with the other treatment component(s) until disease progression or unacceptable toxicity. Randomization was stratified by geographic region, tumor KRAS status, and time to disease progression after beginning first-line treatment (<6 months versus ≥6 months). The major efficacy outcome measure was OS. An additional efficacy outcome measure was PFS. 

A total of 1072 patients were randomized, 536 to the CYRAMZA-treatment group and 536 to the placebo-treatment group. Baseline demographics and disease characteristics were similar between treatment arms. The median age was 62 years (range 21-87); 57% were men; 76% were White and 20% were Asian; 49% had ECOG PS 0; 49% had KRAS mutant tumors; and 24% had <6 months from time to disease progression after beginning first-line treatment. The treatment effect was consistent across the pre-specified stratification factors. 

Efficacy results are shown in Table 14 and Figure 5. 

Figure 5: Kaplan-Meier Curves for Overall Survival in RAISE
The Notch1 signaling pathway plays a crucial role in the development of the central nervous system, governing pivotal functional activities in the brain, such as neurogenesis. Sirt3 is instrumental in managing mitochondrial homeostasis and is essential to cell survival. Dysregulation of these signaling pathways is implicated in the pathogenesis of a wide range of diseases, including neurodegenerative disorders such as stroke. We have previously shown that melatonin significantly improved the perinatal brain damage caused by hypoxia-ischemia (HI) through the activation of several protective mechanisms such as restoring mitochondria status and increasing the hippocampal cell proliferation. This study assessed whether melatonin affects the Notch1 signaling pathway and Sirt3 after neonatal HI. Results show that HI significantly increased Notch1 expression both in hippocampal neurons and glial cells as well as the expression of the key proteins of the pathway NICD, HES1, and c-Myc. Melatonin significantly prevented the Notch1 signaling pathway activation induced by HI, maintaining NICD and HES1 expression to control levels. In the same neurons, melatonin also prevents the Sirt3 depletion caused by HI. In summary, this study provides new insights into the effects of melatonin on the Notch1 signaling pathway and Sirt3 in in vivo neonatal brain ischemia. We suggest that the rapid modulation of the Notch1 signaling pathway and Sirt3 induced by melatonin may support neuronal survival during ischemia.