anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.
The research was carried out by using quantitative research methods, quasi-experimental (pre-test, post-test, follow-up, control group) research method.The study was conducted with patients followed-up in eye, dermatology and rheumatology clinics of 6 state-owned hospitals in Ankara, Turkey. The sample size of the study was calculated with the PASS (Power Analysis and Sample Size) statistical package program. It was calculated that our study could be performed with 5% error and 90% power with 35 interventions and 35 control groups, with 70 patients in total. Thus, the research was completed with 70 patients, 35 interventions and 35 control groups.The 7-session psychoeducation program prepared on the basis of the Roy Adaptation Model was applied to the intervention group once a week for 90-120 minutes. Psychoeducation was conducted in 3 groups of 10-12 people, and make-up sessions were held for those who did not attend two consecutive psychoeducation sessions or did not attend two sessions in total. The contents of the psychoeducation sessions were created by the researcher, based on the Roy Adaptation Model, by examining the relevant literature. After the ethics committee report with the permission number GO16 / 229-21 was obtained from the Non-Interventional Clinical Research Ethics Committee of Hacettepe University, the application permission was obtained from the hospitals where the study will be conducted in order to be able to apply the study. Before starting the intervention, the patients were informed about the purpose and scope of the study, and written informed consent was obtained from the patients who agreed to participate in the study. For the control group, after the necessary information was given to the patients, their written informed consent was obtained.
Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target.
BACKGROUND: Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established.
OBJECTIVES: The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model.
MATERIAL AND METHODS: Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively.
RESULTS: Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα.
CONCLUSIONS: Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.
Tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.They both exert their immunosppressive action by inhibiting the calcinurein in T-lymphoctes. Subsequently,Cyclosporin and tacrolimus are both metabolic substrates for cytochrome P450 (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells by the P-glycoprotein (ABCB1) efflux pump. Different expression of CYP3A4, CYP3A5 and P-glycoprotein causes patient to-patient variability in the absorption, metabolism and tissue distribution of calcineurin inhibitors. This different expression is likely to be at least partially the result of mutations in the genes encoding for these enzymes and drug transporter. This may lead to variable drug concentrations within the systemic circulation and at target sites, influencing drug efficacy. Moreover, it will influence the individual's susceptibility to drug interactions and drug toxicity
Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity and can be continued at investigators discretion at end of treatment. Patients also receive SurVaxM with Montanide ISA-51 SC and sargramostim SC once every 2 weeks for 4 doses. Patients with clinical benefit after 4 doses of SurVaxM and remain free of tumor progression and unacceptable toxicity may receive 3 additional doses on weeks 24, 36, and 48. Additionally, patients undergo blood sample collection, CT scans or MRI scans throughout study.
Aim 1 The main aim is to compare the effects of intensive BP intervention between the intervention and usual care arm on the rate of change in TICS-m per year. The investigators will recruit 4,000 patients over 70 years of age with BP \>130/80 mmHg from 2 diverse health systems and randomize patients within each health system to usual care or to a combination of care with clinical decision support, practice facilitators and Pharm Ds to lower home BP to \< 130/80 mmHg. The primary outcome of this trial will be development cognitive decline as determined by a decrease in TICS-m scores from baseline. As a secondary outcome, the investigators will also measure the development of mild cognitive impairment or dementia in a subset of patients who show a decline of ≥3 points through adjudication.

Aim 2a Determine the potential harms of intensive lowering BP. The investigators aim to recruit 4,000 study participants and compare the effects of lowering home BP below 130/80 mmHg with usual care on hospitalizations, emergency department visits, cardiovascular events, deaths, syncope, falls, fractures, hypotension, electrolyte abnormalities and acute kidney injury. The investigators will capture measures of adherence and health care resource utilization. The investigators will assess QOL in 4,000 patients. The investigators will capture possible harms of lowering BP below 130/80 mmHg. The investigators have chosen clinical outcomes of relevance to all the stakeholders based on prior experience on pragmatic clinical trials and our prior experience in ICD-Pieces. Outcomes will be captured from the telephone assessment by study personnel and electronic health records and/or claims data and reflecting possible harms from all participants will include hospitalizations, emergency department visits, cardiovascular events, deaths, syncope, hypotension, falls, fractures, electrolyte disturbances and acute kidney injury. There will also be capture of adherence by pharmacy refill data. The investigators will capture BP readings from each visit. The investigators will also capture number of encounters with the health system as a measure of health care utilization.

Aim 2b Determine the impact of intensive BP management on QOL. Determine the impact of intensive BP management on QOL. Quality of life (QOL) scores will be obtained using the PROMIS Scale v1.2 - Global Health instrument annually after the administration of the TICS-m.
The present invention relates to newly discovered human histone deacetylases (HDACs), also referred to as histone deacetylase-like polypeptides. The polynucleotide sequences and encoded polypeptides of the novel HDACs are encompassed by the invention, as well as vectors comprising these polynucleotides and host cells comprising these vectors. The invention also relates to antibodies that bind to the disclosed HDAC polypeptides, and methods employing these antibodies. Also related are methods of screening for modulators, such as inhibitors or antagonists, or agonists. The invention also relates to diagnostic and therapeutic applications which employ the disclosed HDAC polynucleotides, polypeptides, and antibodies, and HDAC modulators. Such applications can be used with diseases and disorders associated with abnormal cell growth or proliferation, cell differentiation, and cell survival, e.g., neoplastic cell growth, and especially breast and prostate cancers or tumors.
Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2). Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC). These two drugs may have a synergistic effect on anti-tumor. The purpose of this study is to determine whether Toripalimab with Rituximab is effective and safe for treatment of relapsed refractory CD20 positive diffuse large B-cell lymphoma. This is an exploratory small sample, phase II, single-center clinical trial, which is going to enroll 20 participants.
Subjects will take their assigned study medication (Vaptor 20mg), after at least 10 hours fast together with 240 mL of ambient temperature water at their scheduled dosing time. Those subjects who received Test Drug in first period will receive Reference drug in 2nd period of the study.
Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1, followed by Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2, followed by Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3. Each period was separated out by a 6 to 14-day washout period.
Most patients experience postoperative ileus (POI) after surgery, which is associated with increased morbidity, mortality, and hospitalization time. POI is a consequence of mechanical damage during surgery, resulting in disruption of motility in the gastrointestinal tract. The mechanisms of POI are related to aberrant neuronal sensitivity, impaired epithelial barrier function, and increased local inflammation. However, the details remain enigmatic. Therefore, experimental murine models are crucial for elucidating the pathophysiology and mechanism of POI injury and for the development of novel therapies. Here, we introduce a murine model of POI generated via intestinal manipulation (IM) that is similar to clinical surgery; this is achieved by mechanical damage to the small intestine by massaging the abdomen 1-3 times with a cotton swab. IM delayed gastrointestinal transit 24 h after surgery, as assessed by FITC-dextran gavage and fluorescence detection of the segmental digestive tract. Moreover, tissue swelling of the submucosa and immune cell infiltration were investigated by hematoxylin and eosin staining and flow cytometry. Proper pressure of the IM and a hyperemic effect on the intestine are critical for the procedure. This murine model of POI can be utilized to study the mechanisms of intestinal damage and recovery after abdominal surgery.
INTRODUCTION: Neck pain is a global health problem that can cause severe disability and a huge medical burden. Clinical practice guideline (CPG) is an important basis for clinical diagnosis and treatment. A high-quality CPG plays a significant role in clinical practice. However, the quality of the CPGs for neck pain lacks comprehensive assessment. This protocol aims to evaluate the methodological, recommendation, reporting quality of global CPGs for neck pain and identify key recommendations and gaps that limit evidence-based practice.
METHOD: CPGs from January 2013 to November 2023 will be identified through a systematic search on 13 scientific databases (PubMed, Cochrane Library, Embase, etc) and 7 online guideline repositories. Six reviewers will independently evaluate the quality of CPGs for neck pain by using the Appraisal of Guidelines for Research and Evaluation, the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence and the Reporting Items for Practice Guidelines in Healthcare tools. Intraclass correlation coefficient will be used to test the consistency of the assessment. We will identify the distribution of evidence and recommendations in each evidence-based CPGs for neck pain and regrade the level of evidence and strength of recommendations by adopting the commonly used Grading of Recommendations, Assessment, Development and Evaluations system. The key recommendations based on high-quality evidence will be summarised. In addition, we will categorise CPGs by different characteristics and conduct a subgroup analysis of the results of assessment.
ETHICS AND DISSEMINATION: No subjects will be involved in this systematic review, so there is no need for ethical approval. The finding of this review will be summarised as a paper for publication in a peer-reviewed journal.
PROSPERO REGISTRATION NUMBER: CRD42023417717.
FIELD: immunology. SUBSTANCE: for preparing substance showing high hemagglutinating activity antigen of nematode Trichinella spiralis (molecular mass is from 16 to 20 kDa) is isolated from larvae or mature trichinas by preparative electrophoresis in 10% polyacrylamide gel in tris-glycine-buffer system (pH = 8.6). Protein fraction elution is carried out with 5 mM solution of NaHCO 3 . Prepared substance shows high hemagglutinating activity and can be used in helmintology as diagnostics. EFFECT: improved method of preparing. 1 dwg, 1 tbl
[0718] The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof. is enhanced or evident upon aberrant post--translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.  Figure 1
Chronic kidney disease affects 11% of the US population; over half of those affected have skeletal manifestations of their renal disease. Renal osteodystrophy is a complex disease, in which multiple mineral systems and related hormones play a role, including phosphate homeostasis. Phosphate regulation primarily depends on renal handling of phosphate, which is partly controlled by parathyroid hormone and vitamin D. However, other mediators in this system clearly exist. Recently, evidence has been accruing that one such factor may be FGF23, a protein produced by osteogenic cells. States of excess FGF23 are associated with marked phosphate wasting, hypophosphatemia, osteomalacia, and inappropriately low calcitriol. FGF23 levels are measurable in healthy humans and markedly elevated in patients who require hemodialysis, although its physiologic role in either state is unknown. Some retrospective evidence suggests that FGF23 is affected by phosphate intake. We are performing a pilot study to gather preliminary data describing the response of FGF23 to changes in dietary phosphorus intake in healthy men and in men with moderate renal insufficiency. The specific aims of this pilot study are: 1) To examine the physiologic effects of alterations in dietary phosphorus on FGF23 in healthy subjects; 2) To examine the physiologic response of FGF23 to dietary phosphorus alterations in patients with moderate renal failure; 3) To assess whether serum levels of 1,25-dihydroxyvitamin D vary inversely with those of FGF23 when dietary phosphate is changed; 4) To determine the temporal pattern of calcitropic hormones and FGF23 in response to dietary phosphate changes; and 5) To determine the variability of the changes in serum FG 23 in response to dietary phosphate manipulations. The proposed research plan is a dietary intervention trial in which we will study the response of serum FGF23 levels to diets with varying phosphorus contents in healthy adults and adults with moderate renal insufficiency.
Highly active antiretroviral therapy (HAART) has dramatically improved prognosis and lowered morbidity and mortality rates for HIV infected patients. However, significant drug toxicities, difficulties with patient compliance to HAART regimens, and development of drug resistance highlight the need for less toxic, immune-based strategies. Aldesleukin is a synthetic protein that can increase CD4 counts; it is currently approved by the Food and Drug Administration (FDA) for use in patients with metastatic melanoma and renal cell carcinoma. Previous studies of aldesleukin in HIV infected patients indicated that increased CD4 counts can persist for years after aldesleukin administration, and aldesleukin given with HAART may also lead to significant lowering of viral load. This study will examine the immunologic effects of intermittent cycles of aldesleukin administered with and without HAART as compared to no therapy in HIV infected patients.

This study will last approximately 31 months. Participants will be randomly assigned to one of three groups at study entry. Group A will receive no aldesleukin or HAART. Group B will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Group C will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group C participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). HAART will not be provided by the study. Some Group B and C participants may take part in additional cycles of aldesleukin if they meet certain study criteria.

All participants in this study will have at least 8 study visits; these visits will occur at study entry and Weeks 4, 8, 12, 16, 20, 24, and 32. Blood collection will occur at all visits and will include tests for CD4 count and viral load. Groups B and C will have additional blood collection within 4 days prior to the start of each aldesleukin cycle. On the last day of each aldesleukin cycle, Groups B and C will be assessed for toxicities, adverse events, and adherence to the aldesleukin daily injections; they will also have another blood collection. Group C participants will have an additional blood collection for HIV genotyping after they have completed their third aldesleukin cycle. Extended follow-up visits will occur approximately every 4 months for an additional two years. Blood collection will occur at these visits and will include tests for CD4 count, viral load, and other laboratory tests.
<b><br>Introduction:</b> It is already known that bariatric surgery can improve the health and quality of life of morbidly obese patients of all ages. Our population is getting older. That is why the number of bariatric surgeries among obese people over 65 years of age is systematically increasing.</br> <b><br>Aims:</b> The study aims to analyze the management of patients over 65 years of age in Polish bariatric centers.</br> <b><br>Material and methods:</b> The study was conducted on representatives from the 30 largest bariatric departments in Poland. By collecting surveys, we aimed to analyze changes in qualifications for surgery and care for elderly patients.</br> <b><br>Results:</b> 13 of 30 (43.3%) representatives responded to the survey. The remaining centers did not qualify patients over 65 years old for the surgical treatment of obesity. The mean percentage of patients over 65 who underwent bariatric surgery was 2.75. Most representatives (69.2%) chose SG as the procedure of choice in patients over 65 years of age. According to 84.6% of surgeons, age did not matter when qualifying patients over 65 years of age for BS. The majority of surgeons (53.8%) believed that bariatric surgery in older patients was comparable to the one in younger patients. Nine (69.2%) surgeons believed that there should be no age limit for bariatric surgery.</br> <b><br>Conclusions:</b> Only almost half of the bariatric centers in Poland perform operations on patients over 65 years of age. Most Polish surgeons claim that operations on older and on younger patients have comparable benefits, and that there is no need for age limit.</br>.