syedzayyan/paper_mill_benchmark huggingface dataset:
Yangjing Zhongyu decoction facilitates mitochondrial activity, estrogenesis, and energy metabolism in H2O2-induced human granulosa cell line KGN.

Ethnopharmacological relevant yangjing zhongyu decoction (yjzyd) is a recipe from a chinese classic medical work and has been empirically used in female infertility for hundreds of years, but the mechanisms of yjzyd on facilitating ovarian granulosa cells remain unfold.Aim of the research the purpose of the study is to determine the rewarding effects of yjzyd on h2o2-induced kgn cells, involving mitochondrial activity, estradiol biosynthesis, and energy metabolism.Materials and methods the ingredients of yjzyd were investigated by uplc-esi-ms/ms analysis.The effects of yjzyd and h2o2on cell viability were determined by cck-8.Intracellular ros were assessed by dcfh-da.Intracellular ca2+was detected using fura-4 am.Mitochondrial membrane potential (mmp) was measured by jc-1.The production of energy was assessed by atp.Apoptosis rate was analyzed by annexin v-fitc/pi.Western blotting was used to evaluate the expression of proteins related to energy metabolism, apoptosis, mitochondrial mitophagy, and estrogen biosynthesis.E2levels were measured by elisa.Results 121 compounds were identified in yjzyd by uplc-esi-ms/ms analysis.Yjzyd could enhance mitochondrial activity by suppressing intracellular ros and ca2+, and increasing mmp and atp content.Yjzyd stimulated the expression of anti-apoptosis protein bcl-2 and lowered the early apoptosis rate and the expression of bax.Besides, yjzyd rescued e2secretion and improved the expression of fshr, cyp19a1, and the ratio of p-creb/creb.In addition, yjzyd weakened h2o2-induced mitophagy by compromising the expression of pink1, parkin, beclin1 and p62.Moreover, yjzyd strengthened energy metabolism by increasing atp generation and the expression of sirt1, pgc1α, nrf1, and cox iv.The combination of yjzyd and autophagy inhibitor had a stronger protective effect on energy metabolism.Conclusion this study evaluated the protective effects of yjzyd on h2o2-induced kgn cells.Yjzyd could enhance mitochondrial activity, e2biosynthesis, and energy metabolism.These results strongly indicated that yjzyd might play a role in preserving ovarian granulosa cells and female fecundity.

Journal: Journal of ethnopharmacology (2022)
Publication types: Journal Article
The increase in O2 nodule-conductance under phosphorus deficiency varies among genotypes in Medicago truncatula.

The effect of phosphorus deficiency on plant growth, nodulation, and symbiotic nitrogen fixation as well as, the nodulated-roots oxygen consumption, nodule permeability and conductance to the oxygen diffusion of medicago truncatula-sinorhizobium meliloti symbiosis were studied.Three lines, namely tn6.18, originated from local populations, f83005.5 originated from var (france) and jemalong 6, a reference cultivar from australia, were hydroponically grown in nutrient solution supplied with 5 μmol (p deficient) and 15 μmol (p sufficient: control), under semi-controlled conditions in a glasshouse.A genotypic variation in tolerance to p deficiency was found: tn6.18 was the most tolerant line whereas f83005.5 was the most sensitive.The relative tolerance of tn6.18 was concomitant with the greater p requirement, the higher n2 fixation, the stimulation of nodule respiration and the less increases of conductance to the oxygen diffusion in nodules tissues.The higher p use efficiency for nodule growth and for symbiotic nitrogen fixation was detected in the tolerant line.Results suggest that the tolerance to p deficiency seems to depend on thehost plant ability to reallocate p from both leaves and roots to their nodules.P is needed in high energy demand conditions to maintain adequate nodule activity and prevent negative effects of the o2 excess on the nitrogenase.

Journal: Cellular and molecular biology (Noisy-le-Grand, France) (2022)
Publication types: Journal Article
Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films Using Box-Behnken Design.

The purpose of the present study was to prepare orodispersible films (odfs) loaded with ketoprofen nanoparticles (kt-np).The box-behnken design was constructed in developing and optimizing the ktf-np-odfs.The effect of independent variables: soluplus® concentration (x1, stabilizer), tween 80 concentration (x2, surfactant), and ktf concentration (x3, drug) were studied on the dependent variables: particle size (ps, y1), zeta potential (zp, y2), and the polydispersity index (pdi, y3) of the nps, as well as on the tensile strength (ts, y4) and permeability coefficient (pc, y5) of the ktf-np-odfs.Hydroxypropyl methylcellulose (hpmc e15) and polyethylene glycol (peg 400) were used as the film former polymer and plasticizer, respectively, and their concentrations were kept constant for all formulations.Ktf-nps were prepared by antisolvent precipitation technology.This was followed by the addition of hpmc e15 and peg 400 to prepare the odfs using the solvent-casting method.The ps, pdi, and zp for all the formulations were found in the range of 94 nm to 350 nm, 0.09 to 0.438, and -21.83 m v to -8.03 m v, respectively.The ts and pc of the prepared ktf-np-odfs were found between 1.21 mpa to 3.93 mpa and 3.12 × 10-4cm/h to 34.23 × 10-4cm/h, respectively.The amorphous nature of the ktf-np in the odfs was confirmed by the absence of characteristic crystalline peaks and endothermic events of ktf in x-ray diffraction (xrd) and modulated differential scanning calorimetry (m dsc), respectively.The optimized formulation showed ̴ 4 times higher permeability as compared to the pure ktf.In addition, the dissolution of pure ktf and the optimized ktf-np-odf in p h 1.2 at the end of 60 min was found to be ̴ 30% and ̴ 95%, respectively.Conclusively, ktf-np-odfs can be a promising drug delivery system to counter the issues related to dysphagia and bypass the common side effects, such as the gastric irritation associated with nsaids like ktf.

Journal: Journal of pharmaceutical sciences (2022)
Publication types: Journal Article
Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry.

Introduction to describe clinical characteristics of patients in japan with coronavirus disease 19 (covid-19) and pre-existing rheumatic disease and examine the possible risk factors associated with severe covid-19.Methods adults with rheumatic disease and a covid-19 diagnosis who were registered in the covid-19 global rheumatology alliance (c19-gra) physician-reported registry from japan between 15 may 2020 and 12 may 2021 were included.Multivariable logistic regression models were used to assess factors associated with severe covid-19 progression, defined as death or requiring oxygen inhalation.Results in total, 222 patients were included in the study.Rheumatoid arthritis (48.2%), gout (14.4%), and systemic lupus erythematosus (8.1%) were the most common types of rheumatic disease, 55.1% of patients were in remission and 66.2% had comorbid disease.Most patients were hospitalised (86.9%) for covid-19, 43.3% received oxygen, and 9.0% died.Older age (≥ 65 years), corticosteroid use, comorbid diabetes, and lung diseases are associated with higher risk for severe covid-19 progression (odds ratio (or) 3.52 [95% confidence interval (ci) 1.69-7.33], or 2.68 [95% ci 1.23-5.83], or 3.56 [95% ci 1.42-8.88], and or 2.59 [95% ci 1.10-6.09], respectively).Conclusions this study described clinical characteristics of covid-19 patients with rheumatic diseases in japan.Several possible risk factors for severe covid-19 progression were suggested.Key points • clinical characteristics of 222 adult patients in japan with coronavirus disease 19 (covid-19) and pre-existing rheumatic diseases were described.• most patients were hospitalised (86.9%) for covid-19 in japan, 43.3% received oxygen, and 9.0% died.• the covid-19 characteristics of patients with rheumatic diseases did not show any obvious different pattern from those of the general population in japan.• in this study, older age (≥ 65 years), corticosteroid use, comorbid diabetes, and lung diseases are associated with higher risk for severe covid-19 progression.

Journal: Clinical rheumatology (2022)
Publication types: Multicenter Study;Observational Study;Journal Article
Dynamic Imaging of the Eye, Optic Nerve, and Extraocular Muscles With Golden Angle Radial MRI.

The eye and its accessory structures, the optic nerve and the extraocular muscles, form a complex dynamic system.In vivo magnetic resonance imaging (mri) of this system in motion can have substantial benefits in understanding oculomotor functioning in health and disease, but has been restricted to date to imaging of static gazes only.The purpose of this work was to develop a technique to image the eye and its accessory visual structures in motion.Methods dynamic imaging of the eye was developed on a 3-tesla mri scanner, based on a golden angle radial sequence that allows freely selectable frame-rate and temporal-span image reconstructions from the same acquired data set.Retrospective image reconstructions at a chosen frame rate of 57 ms per image yielded high-quality in vivo movies of various eye motion tasks performed in the scanner.Motion analysis was performed for a left-right version task where motion paths, lengths, and strains/globe angle of the medial and lateral extraocular muscles and the optic nerves were estimated.Results offline image reconstructions resulted in dynamic images of bilateral visual structures of healthy adults in only ∼15-s imaging time.Qualitative and quantitative analyses of the motion enabled estimation of trajectories, lengths, and strains on the optic nerves and extraocular muscles at very high frame rates of ∼18 frames/s.Conclusions this work presents an mri technique that enables high-frame-rate dynamic imaging of the eyes and orbital structures.The presented sequence has the potential to be used in furthering the understanding of oculomotor mechanics in vivo, both in health and disease.

Journal: Investigative ophthalmology & visual science (2017)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
When do people with abdominal symptoms need a fast track referral?

The study herbert a, rafiq m, pham tm, et al.Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the uk: a cohort study.plo s med2021:18;e1003708.to read the full nihr alert, go to:

Journal: BMJ (Clinical research ed.) (2022)
Publication types: Journal Article
N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin t (tn t) and n-terminal pro-brain natriuretic peptide (nt-pro bnp) levels.Both markers may reflect different forms of cardiac involvement in critical illness.Therefore, the aim of our study was to examine the synergistic prognostic potential of nt-pro bnp and high-sensitivity tn t (hs)tn t in unselected critically ill patients.Methods we included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured nt-pro bnp and tn t plasma levels on the day of admission and 72 hours thereafter.Results of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%.Non-survivors showed significantly higher nt-pro bnp and tn t plasma levels as compared with survivors (p<0.01).An elevation of both markers exhibited an additive effect on mortality, as those with both nt-pro bnp and tn t levels above the median had a 30-day mortality rate of 51.0%, while those with both markers below the median had a 16.7% mortality rate (hazard ratio 3.7).These findings were independent of demographic and clinical parameters (p<0.05).Conclusions our findings regarding the individual predictive properties of nt-pro bnp and tn t are in line with literature.However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value.This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Journal: European heart journal. Acute cardiovascular care (2020)
Publication types: Journal Article;Observational Study
Efficacy and safety of monoclonal antibody therapies for relapsing remitting multiple sclerosis: A network meta-analysis.

Several monoclonal antibodies have been licensed for relapsing remitting multiple sclerosis (rrms).It is still unclear which treatment regimen should be recommended due to the lack of head-to-head randomized controlled trials (rcts).This study aims to investigate the relative efficacy and safety of existing monoclonal antibody therapies in treating rrms.Methods we searched pub med, embase, and the cochrane library for rcts of monoclonal antibodies for treatment of rrms.We performed a network meta-analysis to identify evidence comparing monoclonal antibodies with one another, interferon beta-1a (infβ-1a), or placebo in adult patients with rrms.The primary efficacy outcome was annualized relapse rate and the primary safety outcome was incidence rate of serious adverse events.Results a total of 14 eligible studies containing 9412 patients treated with 7 regimens were analyzed.Infβ-1a was the most common comparison treatment and showed an annualized relapse rate of 45.3%.All monoclonal antibody regimens, including natalizumab, natalizumab plus infβ-1a, alemtuzumab, daclizumab, and ocrelizumab, were associated with significant reduction in annualized relapse rate and similar risks of serious adverse events.Cluster analysis showed that natalizumab plus infβ-1a and alemtuzumab performed best in terms of high efficacy and safety.Natalizumab and daclizumab were characterized by high efficacy but relatively high risk of serious adverse events.Ocrelizumab was differentiated by high safety but relatively poor efficacy.Conclusion this network meta-analysis provided a comprehensive summary of efficacy and safety of monoclonal antibodies for rrms, which might provide a reference for treatment.More direct comparison studies are warranted.

Journal: Multiple sclerosis and related disorders (2018)
Publication types: Journal Article;Meta-Analysis
N-of-1 Trials in Pediatric Oncology: From a Population-Based Approach to Personalized Medicine-A Review.

Pediatric oncology is a critical area where the more efficient development of new treatments is urgently needed.The speed of approval of new drugs is still limited by regulatory requirements and a lack of innovative designs appropriate for trials in children.Childhood cancers meet the criteria of rare diseases.Personalized medicine brings it even closer to the horizon of individual cases.Thus, not all the traditional research tools, such as large-scale rcts, are always suitable or even applicable, mainly due to limited sample sizes.Small samples and traditional versus subject-specific evidence are both distinctive issues in personalized pediatric oncology.Modern analytical approaches and adaptations of the paradigms of evidence are warranted.We have reviewed innovative trial designs and analytical methods developed for small populations, together with individualized approaches, given their applicability to pediatric oncology.We discuss traditional population-based and individualized perspectives of inferences and evidence, and explain the possibilities of using various methods in pediatric personalized oncology.We find that specific derivatives of the original n-of-1 trial design adapted for pediatric personalized oncology may represent an optimal analytical tool for this area of medicine.We conclude that no particular n-of-1 strategy can provide a solution.Rather, a whole range of approaches is needed to satisfy the new inferential and analytical paradigms of modern medicine.We reveal a new view of cancer as continuum model and discuss the "evidence puzzle".

Journal: Cancers (2021)
Publication types: Journal Article;Review
Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review.

Importance sarcoidosis is an inflammatory granulomatous disease of unknown cause that affects an estimated 2 to 160 people per 100 000 worldwide and can involve virtually any organ.Approximately 10% to 30% of patients with sarcoidosis develop progressive pulmonary disease.Observation among patients with pulmonary sarcoidosis, the rate of spontaneous remission without serious sequelae ranges from 10% to 82%.However, lung disease progression occurs in more than 10% of patients and can result in fibrocystic architectural distortion of the lung, which is associated with a mortality rate of 12% to 18% within 5 years.Overall, the mortality rate for sarcoidosis is approximately 7% within a 5-year follow-up period.Worldwide, more than 60% of deaths from sarcoidosis are due to pulmonary involvement; however, more than 70% of deaths from sarcoidosis are due to cardiac involvement in japan.Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40%.Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues.Although optimal doses of oral glucocorticoids for pulmonary sarcoidosis are unknown, oral prednisone typically starting at a dose of 20 mg/d to 40 mg/d for 2 to 6 weeks is recommended for patients who are symptomatic (cough, dyspnea, and chest pain) and have parenchymal infiltrates and abnormal pulmonary function test results.Oral glucocorticoids can be tapered over 6 to 18 months if symptoms, pulmonary function test results, and radiographs improve.Prolonged use of oral glucocorticoids may be required to control symptoms and stabilize disease.Patients without adequate improvement while receiving a dose of prednisone of 10 mg/d or greater or those with adverse effects due to glucocorticoids may be prescribed immunosuppressive agents, such as methotrexate, azathioprine, or an anti-tumor necrosis factor medication, either alone or with glucocorticoids combined with appropriate microbial prophylaxis for pneumocystis jiroveci and herpes zoster.Effective treatments are not available for advanced fibrocystic pulmonary disease.Conclusions and relevance sarcoidosis has a mortality rate of approximately 7% within a 5-year follow-up period.More than 10% of patients with pulmonary sarcoidosis develop progressive disease and more than 60% of deaths are due to advanced pulmonary sarcoidosis.Oral glucocorticoids with or without another immunosuppressive agent are the first-line therapy for symptomatic patients with abnormal pulmonary function test results and lung infiltrates.Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues.

Journal: JAMA (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Review
Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure.

Heart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates.Jiashen tablets (jst), a chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure.This study was designed to determine the effect of jst on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach.Materials and methods the chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats.The cardiac functions of rats, including left ventricular ejection fraction (lvef) and fractional shortening (lvfs), left ventricular internal diameter end diastole (lvidd) and end systole (lvids), and interventricular septum thickness in diastole (ivsd) and in systole (ivss), were measured by echocardiography.Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of jst for treating heart failure.Uhplc-qtof-ms/ms coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of jst in the treatment of heart failure.Results jiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat lvef and lvfs and decreasing lvidd, lvids, ivsd, and ivss.Results of biochemical analysis and histopathological examination revealed that jst could reduce the serum lactate dehydrogenase (ldh) activity and the level of nt-pro bnp, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis.Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after jst treatment.These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism.Conclusion the present study illustrated the therapeutic effect of jst for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.

Journal: Frontiers in cardiovascular medicine (2022)
Publication types: Journal Article
Balancing the dental boards.

The gender balance on boards is an important issue because any imbalance represents gender inequality and is not acceptable.We describe data that we have gathered on the current balance of the uk dental boards and then outline potential ways forward to address any imbalance.

Journal: British dental journal (2021)
Publication types: Journal Article