anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure.
METHODS: This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation.
CONCLUSION: The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.
Coronary artery spasm (CAS) plays an important role in the pathogeneses of various ischemic heart diseases and has gradually become a common cause of life-threatening arrhythmia. The specific molecular mechanism of CAS has not been fully elucidated, nor are there any specific diagnostic markers for the condition. Therefore, this study aimed to examine the specific molecular mechanism underlying CAS, and screen for potential diagnostic markers. To this end, we successfully constructed a rat CAS model and achieved in vitro culture of a human coronary-artery smooth-muscle cell (hCASMC) contraction model. Possible molecular mechanisms by which protein kinase C (PKC) regulated CAS through the C kinase-potentiated protein phosphatase 1 inhibitor of 17 kDa (CPI-17)/myosin II regulatory light chain (MLC2) pathway were studied in vivo and in vitro to screen for potential molecular markers of CAS. We performed hematoxylin and eosin staining, myocardial zymogram, and transmission electron microscopy to determine myocardial and coronary artery injury in CAS rats. Then, using immunohistochemical staining, immunofluorescence staining, and Western blotting, we further demonstrated a potential molecular mechanism by which PKC regulated CAS via the CPI-17/MLC2 pathway. The results showed that membrane translocation of PKCα occurred in the coronary arteries of CAS rats. CPI-17/MLC2 signaling was observably activated in coronary arteries undergoing CAS. In addition, in vitro treatment of hCASMCs with angiotensin II (Ang II) increased PKCα membrane translocation while consistently activating CPI-17/MLC2 signaling. Conversely, GF-109203X and calphostin C, specific inhibitors of PKC, inactivated CPI-17/MLC2 signaling. We also collected the coronary artery tissues from deceased subjects suspected to have died of CAS and measured their levels of phosphorylated CPI-17 (p-CPI-17) and MLC2 (p-MLC2). Immunohistochemical staining was positive for p-CPI-17 and p-MLC2 in the tissues of these subjects. These findings suggest that PKCα induced CAS through the CPI-17/MLC2 pathway; therefore, p-CPI-17 and p-MLC2 could be used as potential markers for CAS. Our data provide novel evidence that therapeutic strategies against PKC or CPI-17/MLC2 signaling might be promising in the treatment of CAS.
Topical insulin has been proved recently to enhance the corneal reepithelization rate and manage neurotrophic corneal ulcers unresponsive to conventional treatments. However, its effectiveness on corneal epithelial wound healing in patients who received photorefractive keratectomy (PRK) has not been reported. In this study, we plan to perform a prospective non-randomized study to determine the efficacy and safety of topical insulin as a primary treatment for a corneal epithelial defect in patients undergoing the PRK and compare that to autologous serum eye drops. The study eye will receive either the insulin or the serum eye drops, in addition to the conventional treatment, while the control eye will have the standard treatment. For each eligible candidate, the eye with a higher depth of ablation will be the study eye. If even ablation depth in both eyes, the right eye will be selected. The conventional postoperative eye drops include topical moxifloxacin 0.5% (Vigamox; Alcon Laboratories) four times per day, artificial tears (Systane Ultra; Alcon) every two hours, Dexamethasone 0.1% (Maxidex; Alcon Laboratories) four times daily for one month followed by fluorometholone 0.1% (Efemyo; OrchidiaLaboratories) four times daily for another two to four weeks depending on refraction and haze level. In study eyes, the patients receive either topical insulin eye drops or autologous serum in addition to conventional postoperative eye drops until complete epithelial healing. The duration for the corneal surface to completely re-epithelize, the grade of postoperative corneal haze, the incidence of corneal complications due to delayed surface re-epithelization (e.g. infectious corneal ulcer, corneal melting, sterile corneal ulcer, corneal neovascularization), and the distant corrected visual acuity will be compared between these three groups.
During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti-thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood-borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze-dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable.
A tool for aiding a user author labels for drugs. The tool receives inputs that define requirements for a label, or aggregated requirements for a set of related labels. The requirements may be derived from inputs specifying values of label attributes and then be used to identify fields to appear in each of one or more labels to be generated. Information on fields may be used to dynamically render an interface through which a user may specify text strings to appear in each field when label text is generated. Input elements of the interface may be populated with lists of options identified based on the requirements. The requirements may also be used in generating similar labels and assessing the impact of changes, such as to regulatory requirements. The tool may be particularly useful for authoring labels for clinical trials in which multiple label formats for multiple countries may be generated.
Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges.
METHODOLOGY All subjects will be admitted fasting to the Clinical Trial Unit at Århus Community Hospital at 8 a.m. A Gastrointestinal tube will be placed in Duodenum distal to papilla Vaterii with a pH of approximately 7.0 as measured by the pH meter distal in the tube. An indwelling catheter for glucose infusion (20 %) in cases of hypoglycaemia will be placed in an antecubital vein. In the contralateral anticubital vein a catheter will be placed for blood sampling. All subjects will have 4 tests with duodenal infusion of the insulin Aspart solution. The first 4 volunteers will receive 4 doses of insulin Aspart solution in 1 ml (150, 300, 600 and 1000 IU) with 3-6 hours apart. Blood sampling for Insulin Aspart, total insulin, and glucose (Beckmann apparatus) will be done every 10 minutes the first two hours, and then every 20 minutes. When final the subjects will receive a meal before leaving the hospital.

Based on data from the pilot a dose will be determined for the remaining 8 subjects. These will then based again on results from the pilot on two separate study days receive 4 infusions with 3-6 hours split. Two infusions will be at pH 7 and two infusions will be more proximal at a pH of 5.5 (two different insulin concentrations but the same dose given at the two places in Duodenum). Frequency and interval of blood sampling in the second part will be determined by results from the pilot study. For comparison with the clinical situation and estimation of bioavailability all subjects will receive a subcutaneous and an intravenous (iv) bolus injection of 6 IU of insulin Aspart. The iv injection will be followed by blood sampling for three hours as above, but every 5 minutes the first two hours, and the sc injection will be followed by blood sampling for three hours as above, but again with 10 minutes interval the first two hours.
XATMEP can cause severe and potentially irreversible hepatotoxicity including fibrosis, cirrhosis, and fatal liver failure. Avoid use of XATMEP in patients with chronic liver disease. 

Assess liver function prior to initiating XATMEP and monitor liver function tests during treatment. Interrupt or discontinue XATMEP as appropriate. Transient asymptomatic acute liver enzyme elevations are common and are not predictive of subsequent hepatic disease. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis.

Other risk factors for hepatotoxicity include alcoholism, obesity, diabetes, hyperlipidemia, previous significant exposure to liver toxins, history of liver disease, family history of inheritable liver disease, persistent abnormal liver chemistry findings, duration of therapy, and advanced age.
INTRODUCTION: Flap fixation significantly reduces the incidence of seroma formation after mastectomy. Previous studies have compared running sutures, interrupted sutures, and tissue glue application with conventional wound closure. A recent systematic review with network meta-analysis showed running sutures to be the most optimal technique; however, direct comparisons and high adequate scientific evidence are lacking. This prospective trial aimed to directly compare running sutures with interrupted sutures to determine which technique of flap fixation using sutures is superior.
METHODS: This trial will combine a retrospective cohort of patients undergoing flap fixation using interrupted sutures from a previous trial, with a randomised prospective cohort with patients undergoing flap fixation using running sutures or flap fixation using interrupted sutures. This study design was chosen to acquire a sample size with sufficient power and the ability to conduct this study in an acceptable time frame. The primary endpoint is the incidence of complications requiring interventions, including clinically significant seroma, infections and haemorrhagic complications. Secondarily, the length of the procedure and cosmetic results will be compared.
CONCLUSIONS: This is the first trial comparing two suturing techniques for flap fixation after mastectomy. Results will be used to optimise flap fixation techniques for these patients to prevent seroma formation.
Sleep restriction increases evening cortisol and decreases testosterone. These are the main catabolic and anabolic hormones in men, respectively. This catabolic-anabolic imbalance likely leads to metabolic and reproductive ill-health. The hypothalamic-pituitary-end organ (adrenal or testis) mechanisms that must underpin these changes are unknown. This study will administer drugs to clamp the function of each of these nodes to determine the regulatory changes that have occurred with sleep restriction. Even though the study is randomized order in design, the main comparison is before and after sleep restriction under each of these clamp conditions. Participants are admitted to the chronobiology laboratory where they are given 1 night of 10 hours sleep opportunity, followed by 4 nights of 4 hours sleep opportunity. Up to 80 participants (assuming twenty different participant for each of the 4 clamp conditions) can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 20 participants may be required. Urn randomization will be used to ensure that 20 different participants are involved in each of the 4 conditions.
HBV-infected infants in the treatment group were treated with LAM (4 mg/kg/d) before 1 year of age, and then combined with regular interferon (intramuscular or subcutaneous injection, 3-6 million U/m2 body surface area, every other day, with a starting dose of 3 million U/m2 body surface area, which was adjusted according to the specific tolerances of the children during the course of the treatment) if they were still HBV DNA and/or HBsAg-positive at the end of the 1st year of age. The course of interferon treatment is 52 weeks.
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide which is often seen in patients with metabolic abnormalities such as those with obesity and insulin resistance. On the other hand, sarcopenia is a generalized and progressive skeletal muscle disorder characterized by low muscle strength, low muscle quality, low physical performance, or a combination of the three. Both disease entities share several underlying risk factors and pathophysiologic mechanisms. These include: (1) cardiometabolic overlaps such as insulin resistance, chronic systemic inflammation, decreased vitamin D levels, sex hormone modifications; (2) muscle-related factors such as those mitigated by myostatin signaling, and myokines (i.e., irisin); and (3) liver-dysfunction related factors such as those associated with growth hormone/insulin-like growth factor 1 Axis, hepatokines (i.e., selenoprotein P and leukocyte cell-derived chemotaxin-2), fibroblast growth factors 21 and 19 (FGF21 and FGF19), and hyperammonemia. This narrative review will examine the pathophysiologic overlaps that can explain the links between NAFLD and sarcopenia. Furthermore, this review will explore the emerging roles of nonpharmacologic (e.g., weight reduction, diet, alcohol, and smoking cessation, and physical activity) and pharmacologic management (e.g., roles of β-hydroxy-β-methylbutyrate, branched-chain amino acid supplements, and testosterone therapy) to improve care, intervention sustainability, and acceptability for patients with sarcopenia-associated NAFLD.
BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant, rapidly progressing tumor of the bile duct. Owing to its chemoresistance, it always has an extremely poor prognosis. Therefore, detailed elucidation of the mechanisms of chemoresistance and identification of therapeutic targets are still needed.
METHODS: We analyzed the expression of MBD2 (Methyl-CpG-binding domain 2) in CCA and normal bile duct tissues using the public database and immunohistochemistry (IHC). The roles of MBD2 in CCA cell proliferation, migration, and chemoresistance ability were validated through CCK-8, plate cloning assay, wound healing assays and xenograft mouse model. In addition, we constructed a primary CCA mouse model to further confirm the effect of MBD2. RNA-seq and co-IP-MS were used to identify the mechanisms by how MBD2 leads to chemoresistance.
RESULTS: MBD2 was upregulated in CCA. It promoted the proliferation, migration and chemoresistance of CCA cells. Mechanistically, MBD2 directly interacted with WDR5, bound to the promoter of ABCB1, promoted the trimethylation of H3K4 in this region through KMT2A, and activated the expression of ABCB1. Knocking down WDR5 or KMT2A blocked the transcriptional activation of ABCB1 by MBD2. The molecular inhibitor MM-102 targeted the interaction of WDR5 with KMT2A. MM-102 inhibited the expression of ABCB1 in CCA cells and decreased the chemoresistance of CCA to cisplatin.
CONCLUSION: MBD2 promotes the progression and chemoresistance of CCA through interactions with WDR5. MM-102 can effectively block this process and increase the sensitivity of CCA to cisplatin.
BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT).
METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching.
RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort.
CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.
FIELD: veterinary microbiology. SUBSTANCE: strain of bacterium Salmonella enteritidis = 22 shows morphological, cultural and enzymatic properties that are typical for genus Salnonella. By serological properties the proposed strain is agglutinated with salmonellosis monoreceptor sera 09 (1 and 5 complex) H-G. The strain is producer of endotoxin and hemolysine, it shows protein structure and nucleoitide composition of its DNA (% GC) - 53.1. It comprises plamids with molecular mass 60 mDa and is lyzed by polyvalent bacteriophage. Virulent properties: value LD 50  for white mice in intraperitoneal administration is 2.4 x 10 6  live microbe cells. The strain is pathogenic for newborn calves and oral infection in the dose 10 billions microbe cells diarrhea is evident in 24 h and death of animal - in 2-3 day. Concentration of microbe cells in culturing the strain is 40-50 billions by optical turbidity standard GISK named after K. A. Tarasevich, protective effect against infection with virulent strains is on 5-7 day. The strain is useful for preparing vaccines against salmonellosis in animals and for preparing diagnostic preparation and hyperimmune curative sera and globulins. EFFECT: valuable biological and medicinal properties of strain. 1 ex
Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective β1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.
Multivalent scaffolds configured to facilitate drug release upon exposure to a stimulus, such as heat, or light, are described herein. The multivalent scaffolds are covalently bound to a moiety that is susceptible to decomposition upon exposure to stimulus. The moiety releases HNO upon decomposition. In some embodiments, the moiety is in turn linked to an agent to be delivered, such as a therapeutic agent, which is released from the multivalent scaffolds when the moiety decomposes. In some embodiments, the moiety is a 1,2-oxazine moiety. In some embodiments, the multivalent scaffold is a polymer. A plurality of 1,2-oxazine moieties can be covalently bound as side chains to the backbone of the polymer.