anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Fatty acid omega hydroxylase P450s consist of enzymes that hydroxylate various chain-length saturated and unsaturated fatty acids (FAs) and bioactive eicosanoid lipids. The human cytochrome P450 gene 4 family (CYP4) consists of 12 members that are associated with several human diseases. However, their role in the progression of metabolic dysfunction-associated fatty liver disease (MASLD) remains largely unknown. It has long been thought that the induction of CYP4 family P450 during fasting and starvation prevents FA-related lipotoxicity through FA metabolism to dicarboxylic acids that are chain-shortened in peroxisomes and then transported to the mitochondria for complete oxidation. Several studies have revealed that peroxisome succinate transported to the mitochondria is used for gluconeogenesis during fasting and starvation, and recent evidence suggests that peroxisome acetate can be utilized for lipogenesis and lipid droplet formation as well as epigenetic modification of gene transcription. In addition, omega hydroxylation of the bioactive eicosanoid arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) is essential for activating the GPR75 receptor, leading to vasoconstriction and cell proliferation. Several mouse models of diet-induced MASLD have revealed the induction of selective CYP4A members and the suppression of CYP4F during steatosis and steatohepatitis, suggesting a critical metabolic role in the progression of fatty liver disease. Thus, to further investigate the functional roles of CYP4 genes, we analyzed the differential gene expression of 12 members of CYP4 gene family in datasets from the Gene Expression Omnibus (GEO) from patients with steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. We also observed the differential expression of various CYP4 genes in the progression of MASLD, indicating that different CYP4 members may have unique functional roles in the metabolism of specific FAs and eicosanoids at various stages of fatty liver disease. These results suggest that targeting selective members of the CYP4A family is a viable therapeutic approach for treating and managing MASLD.
BACKGROUND: It has been proven that immune disorders are one of the vital risk factors of recurrent pregnancy loss (RPL), and the presence of food intolerance seems to play an essential role in this. However, the impact of immune status induced by food intolerance on RPL has not been reported. This study utilized a targeted diet avoiding food intolerance as much as possible for each participant to investigate their effects on pregnancy outcomes in RPL patients with positive autoimmune markers.
METHODS: From January 2020 to May 2021, fifty-eight patients with RPL were enrolled. They were divided into two groups based on the presence of autoantibodies: the autoantibody-positive group (AP, n = 29) and the autoantibody-negative group (AN, n = 29). Their food-specific immunoglobulin (Ig) G antibodies for 90 foods were tested using enzyme-linked immunosorbent assay (ELISA). The levels of immune parameters and the presence of gastrointestinal discomforts (diarrhea or constipation, eczema, and mouth ulcers) were recorded before and after dietary conditioning, followed by the analysis of pregnancy outcomes.
RESULTS: Compared to the AN group, the patients in the AP group showed immune disorders at baseline, such as reduced levels of IL-4 and complement C3, and increased levels of IL-2 and total B cells. These parameters within the AP group were significantly improved after dietary conditioning that avoided food intolerance, while no significant changes were observed in the AN group. Patients in the AP group had significantly higher food-specific IgG antibodies for cow's milk (89.66% vs. 48.28%, p < .001), yolk (86.21% vs. 27.59%, p < .001), bamboo shoots (86.21% vs. 44.83%, p < .001) compared to those in the AN group. Additionally, gastrointestinal discomforts including diarrhea or constipation, eczema, and mouth ulcers were more common in the AP group than in the AN group. After 3-month dietary conditioning, these significantly improved characteristics were only observed in the AP group (p < .001). Finally, the baby-holding rate was higher in the AP group compared to the AN group (p < .05).
CONCLUSIONS: The RPL patients in the AN group did not exhibit immune disorders, whereas those in the AP group experienced immune disorders and gastrointestinal discomforts. For patient with positive autoantibodies, dietary intervention may mitigate immune disorders and gastrointestinal discomforts, presenting a promising approach to enhance pregnancy outcomes.
Following bradykinin challenge, intravenous administration of FIRAZYR caused dose and time-dependent inhibition of development of bradykinin-induced hypotension, vasodilation, and reflex tachycardia in healthy young subjects. FIRAZYR intravenous doses of 0.4 and 0.8 mg/kg infused over 4 hours inhibited response to bradykinin challenge for 6 to 8 hours following completion of the infusion. Based on exposure-response analysis, a subcutaneous dose of 30 mg FIRAZYR is predicted to be effective against bradykinin challenge for at least 6 hours. The clinical significance of these findings is unknown.

The effect of FIRAZYR 30 and 90 mg following a single subcutaneous injection on QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg) four-period crossover thorough QT study in 72 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo adjusted, baseline-corrected QTc based on individual correction method (QTcI) was below 10 ms, the threshold for regulatory concern. The dose of 90 mg is adequate to represent the high exposure clinical scenario.
Diabetes is associated with increased platelet activation, elevated plasma fibrinogen levels and impaired fibrinolysis, factors which may contribute to the elevated risk of cardiovascular disease (CVD) in these patients. Increased platelet activation in patients with diabetes is reflected by elevated levels of platelet microparticles, which are small circulating procoagulant vesicles shed from the platelet membrane upon activation. CVD in these patients may start as early as in the age of 25-30 years and the course is often aggressive and with poor prognosis. Treatment with a daily low dose of acetylsalicylic acid (aspirin 75 mg) is one of the cornerstones in management of CVD in non-diabetic patients; however, the effect seems reduced in patients with diabetes. The mechanisms behind this treatment failure with aspirin in diabetes patients are unclear. Aspirin is a complex drug with multiple effects. The most well known is acetylation and inhibition of platelet cyclooxygenase (COX), but COX-independent mechanisms may also of importance in protection of cardiovascular complications. One such mechanism is alteration of the fibrin/fibrinogen properties and the fibrin network structure, possibly through acetylation of the lysine residues in the fibrinogen molecule involved in crosslinking of fibrin. The fibrin network structure seems important in development of atherothrombotic events, as individuals at high risk of CVD, including patients with type 1 diabetes, as well as patients with manifest CVD have a tighter and less permeable fibrin network structure. The altered fibrin network in patients with type 1 diabetes may in part be due to increased fibrinogen glycation, which may occur on lysine residues. Treatment with aspirin increases fibrin network permeability in non-diabetic subjects. However, the effect of aspirin on fibrin network permeability in patients with diabetes is unclear. Possible competition between acetylation and glycation on lysine residues in the fibrinogen molecule might contribute to the reduced preventive effect of aspirin in management of CVD in patients with diabetes and higher doses of aspirin might therefore be required in these patients.

Our hypothesis was that glycation and acetylation occur at the same binding sites in the fibrinogen molecule. Thus, poor glycemic control and increased glycation may lead to lower acetylation of the fibrinogen molecule than during good glycemic control in turn leading to an altered fibrin network.

The aims of the present study were to analyse the effects of low (75 mg) and high dose (320 mg) aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim), and to investigate the possible influence of the glycemic control (secondary aim). As platelet microparticles may influence the fibrin formation \[17, 18\] and since aspirin has well-known effects on platelet function, we also measured plasma concentrations of platelet microparticles.
Provided is a compound, represented by formula (1) below, useful for treating cancer or the like. In the formula, R 1  and R 3 -R 8  each independently indicate a hydrogen atom or an alkyl group. R 2  indicates a hydrogen atom or a group represented by －OR a  or the like. R 9  indicates a group represented by －C(O)NR e R f  or the like. R a , R e , and R f  each independently indicate a hydrogen atom, an arylalkyl group that may have a substituent, a heteroarylalkyl group, or the like. In addition, provided are: a production method that enables the compound to be produced with high efficiency; and a pharmaceutical composition containing the compound as an active ingredient.
Primary dysmenorrhea, the commonly occurring gynecological issue faced by young girls. It severely affects quality of female life. It leads to fatigue, psychological issues, lack of interest in selfcare and daily activities that results in absenteeism at work and educational institutes. It also badly affects academic performance and extra-curricular activities. Different pharmacological and non-pharmacological interventions are being used for reducing its negative effects, such as effleurage abdominal massage intend to decrease the problems faced by students as a result of this frightening issue. Here the question arises for health professionals that effleurage abdominal massage has any effect on pain and quality of life in primary dysmenorrhea among university students or not? To find out the answer of this question a study will be conducted with an objective to evaluate the effects of effleurage abdominal massage on pain and quality of life in primary dysmenorrhea among university students. This study holds considerable implications in addressing potential adverse effects associated with pharmacological analgesic agents, thereby mitigating pain, lack of interest in work and enhancing functional capacity, hence improving quality of life. Moreover, it is anticipated to contribute to the reduction of healthcare costs.
The invention provides a drug carrier capable of efficiently targeting macrophages, a preparation method thereof and application thereof in disease treatment. The drug carrier comprises bacterial biological vesicles, wherein drug macromolecules are loaded in the bacterial biological vesicles, and two targeting elements, namely an element for targeting and identifying tumor tissues and an element for targeting and identifying macrophages are modified on the surface of the drug carrier. In the process of producing the bacterial bio-vesicles through physical extrusion, the loading of the internal drug macromolecules and the modification process of the surface targeting elements are completed, so that the loading and delivery efficiency of the drugs is improved. Meanwhile, the yield of the bacterial biological vesicle is hundreds of times that of the bacterial exocrine vesicle under the same condition. Since the drug macromolecules are produced endogenously by bacteria, selection of the appropriate engineered bacteria will allow for continuous expression of the desired drug. The drug carrier provides a new choice for the current treatment of tumors, and can be used for treating malignant tumors including breast cancer and colorectal cancer.
BACKGROUND: Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction (HFpEF) patients with obesity.
METHODS: A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management.
RESULTS: Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns.
CONCLUSION: Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.
Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250-300 households) were defined in the catchment population of twelve health facilities. Children aged 6-18 months were recruited n 1680. The intervention included a daily ration of 50 g - locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + -4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from -1·13(2·2 sd) at baseline to -0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.
Acupressure mats are promoted as stress management tools for easy and effective self-application, promising reduced stress and increased well-being. However, the scientific evidence for these effects is based on few experimental studies and lacks the examination of acupressure mats as a solitary relaxation tool. Our study aimed to examine which changes in stress and well-being can be expected from the use of acupressure mats by healthy young people on the subjective and psychophysiological level. Unexperienced participants practiced relaxation for three weeks either with an acupressure mat or without any tools (active control group [CG]). As a results, subjective well-being and stress decreased, while sleep quality and concentration endurance increased across groups. Blood pressure (BP), heart rate (HR), pain threshold and pain tolerance did not change significantly from pre- to post-training measurements. Most importantly, no significant differences were found between groups, indicating that training with an acupressure mat yielded no superior effects compared with an active control condition in healthy young students. As a conclusion, taking time to relax has some but limited beneficial effects on the subjective levels independent of the specific method for healthy students. Potential beneficial effects of acupressure mats might be bound to specific impairments, such as tension pain.
Bladder cancer is the second most common malignancies over the world. At initial diagnosis, the cases with muscle-invasive bladder cancer (MIBC) accounts nearly 20% of all bladder cancer patients. And 40% of non-muscle-invasive bladder cancer could develop to MIBC. Currently, radical cystectomy (RC) is the golden standard to manage MIBC. Yet, it brings severe surgical injuries and post-surgical complications which impair life quality of the patients. Recently, bladder-preserving treatment based gradually becomes the second choice for MIBC. It consists of maximal transurethral resection of bladder tumor (TURBT) and chemoradiation. A series of clinical trials and meta-analyses supported that the bladder-preserving treatment has a similar therapeutic effect compared with RC. But it is noteworthy that this treatment mode does not really avoid surgery. TURBT could also cause complications, such as haemorrhage, infection, perforation, and even tumor dissemination. Moreover, the incidence of serious toxicities brought by concurrent chemoradiation is as high as 36%. In actual clinical work, it is hard for more than half patients to complete chemoradiation of standard intensity. Additionally, many patients are unsuitable for bladder preservation, including those with T stage \> T2, diameter \> 5 cm, hydronephrosis and positive lymph nodes. Hence, it calls for improvement of current bladder preservation mode, to make more MIBC patients receive radical treatment which brings better therapeutic experience and life quality.

Many lab studies indicated that formation and progression of bladder cancer is a process of mutation accumulation. It provides biological fundamentals for immune checkpoint inhibitors, such as anti-programmed cell death protein 1 (anti-PD-1) antibodies. Based on available clinical studies, anti-PD-1 antibodies exhibits ideal therapeutic effects in bladder cancer of different stages and has an incidence of toxicities as low as 13%. Its toxicities mainly include arthralgia and hyponatremia, which are well tolerated. Currently, there are more than 10 clinical trials trying anti-PD-1 antibodies for bladder preservation. However, the treatment modes in most of them still contain TURBT. This phase 2 trial intended to evaluate the therapeutic and adverse effects of a non-surgical bladder-preserving treatment mode consisting of anti-PD-1 antibodies and chemoradiation, in a small patient cohort with MIBC. The results might provide an effective, non-invasive and low-toxic choice which improves patient experience and realizes bladder preservation.
Patients receive daratumumab IV over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days.
PURPOSE:To facilitate the design, manufacture, maintenance and extension by carrying out the analysis/development processing of an auxiliary function signal as well as the action ending process of an actuator within an NC device. CONSTITUTION:When a tailstock 4 moves forward or backward, a forward movement confirming switch 5 or a backward movement confirming switch 6 works. Then the forward or backward movement confirming signal undergoes the end processing through an end processing part 9 of an NC device 1. Three types of signals, i.e., modal ON and OFF signals and one-shot signal are outputted from an output signal line in response to the auxiliary function signal sent to an analysis/development processing part 8 from the device 1. Thus the part 8 performs the analysis/development processing in accordance with said auxiliary function signal. Then the modal ON signal (forward movement command), the modal OFF signal (backward movement command) or the one- shot signal serving as an action command of a robot are outputted from the output signal line. Thus it is possible to facilitate the design, manufacture, maintenance and extension respectively.
Participants in this arm will be prompted on their phones 4x/day, to report on activities, mood, suicidal ideation, distress level and ESP use since the last prompt. They will also participate in brief assessment visits conducted weekly for the first 6 weeks and then biweekly for the remaining 9 weeks of the term.
BACKGROUND: An important chance of nosocomial acquired infections are caused by the opportunistic bacterium Klebsiella pneumoniae. Urine, wound, sputum, and blood samples were collected from all patients. This study aimed to detect the antibiotic resistance profile, the frequency of MDR, XDR, PDR, and detection of efflux pump and outer membrane permeability genes in K. pneumoniae isolates.
METHODS: One hundred twenty samples were collected from patients who were admitted to the Ramadi Teaching Hospitals in Al-Anbar Governorate. Fifty five of K. pneumoniae strains were collected from patients. The VITEK®2 Compact B System was used to detect the antibiotic resistance pattern of studied bacteria. The isolates were classified as MDR, XDR, or PDR based on established guidelines. The data were analyzed using Clinical and Laboratory Standards Institute (CLSI) breakpoints. PCR was used to detect the efflux pumps and porins genes.
RESULTS: Out of the 120 samples studied, 45.83 % (55) tested positive for K. pneumoniae. The isolates displayed the greatest amount of resistance to cefazolin, ceftriaxone (98.2 %), ampicillin (100 %), and ceftazidime, cefepime (90.9 %). 20 % of the isolates were found to produce metallo-lactamases, and 41.81 % tested positive for extended-spectrum beta-lactamases. Overall, the rates of multi-drug resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) isolates were 57.2 %, 10.9 %, and 9.09 %, respectively. Additionally, the prevalence of efflux pump genes acrAB, mdtK, and tolC were 94.54 %, 14.54 %, and 89.09 %, respectively, while the porin-encoding genes ompK35 and ompK36 were found in 96.36 % and 98.18 % of the isolates.
CONCLUSION: This investigation concluded that the study isolates had a high degree of antibiotic resistance heterogenicity. High frequencies of resistance to ampicillin, cefazolin, and ceftriaxone are present in study isolates. Most strains were categorized as MDR strains, with six being XDR strains and five being PDR strains. One of the main routes of antibiotic resistance in multidrug-resistant K. pneumoniae strains is through the acrAB efflux system. The high prevalence of the acrAB, tolC, ompk35, and ompK36 genes were increases the ability of these isolates combat antimicrobial treatments.
The patient will be asked to sit on the chair as fast as possible, so that the chair, which has a 46 cm height, will be crossed in the chest. The stopwatch is started with the command given to the patient and stopped in 30 seconds. The number of repetitions will be recorded.