syedzayyan/paper_mill_benchmark huggingface dataset:
Mapping in vivo microclimate pH distribution in exenatide-encapsulated PLGA microspheres.

The p h inside the aqueous pores of poly(lactic-co-glycolic acid) (plga) microspheres, often termed microclimate p h (μp h), has been widely evaluated in vitro and shown to commonly be deleterious to p h-labile encapsulated drug molecules.However, whether the in vitro μp h is representative of the actual in vivo values has long been remained a largely unresolved issue.Herein we quantitatively mapped, for the first time, the in vivo μp h distribution kinetics inside degrading plga microspheres by combining two previously validated techniques, a cage implant system and confocal laser scanning microscopy.Plga (50/50, mw = 24-38 k da, acid-end capped and ester-capped) microsphere formulations with and without encapsulating exenatide, a p h-labile peptide that is known to be unstable when p h > 4.5, were administered to rats subcutaneously via cage implants for up to 6 weeks.The results were compared with two different in vitro conditions.Strikingly, the in vivo μp h developed similarly to the low microsphere concentration in vitro condition with 1-μm nylon bags but very different from conventional high microsphere concentration sample-and-separate conditions.Improved maintenance of stable external p h in the release media for the former condition may have been one important factor.Stability of exenatide remaining inside microspheres was evaluated by mass spectrometry and found that it was steadily degraded primarily via p h-dependent acylation with a trend that slightly paralleled the changes in μp h.This methodology may be useful to elucidate p h-triggered instability of plga encapsulated drugs in vivo and for improving in vivo-predictive in vitro conditions for assessing general plga microsphere performance.

Journal: Journal of controlled release : official journal of the Controlled Release Society (2022)
Publication types: Journal Article;Research Support, U.S. Gov't, P.H.S.
CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT.

Type 3 secretion system (t3ss) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many gram-negative pathogenic bacteria, including pseudomonas aeruginosa.Exotoxin t (exo t) is the only t3ss effector protein that is expressed in all t3ss-expressing p.Aeruginosa strains.Here we show that t3ss recognition leads to a rapid phosphorylation cascade involving abl / pkcδ / nlrc4, which results in nlrc4 inflammasome activation, culminating in inflammatory responses that limit p.Aeruginosa infection in wounds.We further show that exo t functions as the main anti-inflammatory agent for p.Aeruginosa in that it blocks the phosphorylation cascade through abl / pkcδ / nlrc4 by targeting crk ii, which we further demonstrate to be important for abl transactivation and nlrc4 inflammasome activation in response to t3ss and p.Aeruginosa infection.

Journal: Nature communications (2022)
Publication types: Journal Article
TBK1 of black carp plays an important role in host innate immune response against SVCV and GCRV.

Tank-binding kinase 1 (tbk1) plays a pivotal role in the induction of type i ifns in higher vertebrates.To explore the function of tbk1 in teleost, tbk1 of black carp (mylopharyngodon piceus) was cloned and characterized in this paper.The full-length c dna of black carp tbk1 (bc tbk1) consists of 2857 nucleotides and the predicted bc tbk1 protein contains 727 amino acids, which includes an n-terminal kinase domain (kd), an ubiquitin-like domain (uld) and two c-terminal coiled-coils.The transcription of bc tbk1 was constitutively detected in all the selected tissues and bc tbk1 m rna level was increased in all selected tissues in response to svcv or gcrv infection except that in muscle post gcrv invasion.The transcription of bc tbk1 in mylopharyngodon piceus fin (mpf) cells was up-regulated by the stimulation of svcv, gcrv or poly (i:c) but not by lps treatment.Bc tbk1 migrated around 80 k da in immunoblot assay and was identified as a cytosolic protein by immunofluorescence staining.Bc tbk1 showed strong ifn-inducing ability in reporter assay and presented strong antiviral activity against both gcrv and svcv in epc cells.The reporter assay demonstrated that traf6 of black carp (bc traf6) up-regulated bc tbk1-induced ifn expression and the subcellular distribution of bc tbk1 overlapped with that of bc traf6 when these two proteins were co-expressed in epc cells.Taken together, our study support the conclusion that bc tbk1 plays an important role in the antiviral innate immune response of black carp against svcv and gcrv, in which its activity was positively regulated by bc traf6.

Journal: Fish & shellfish immunology (2017)
Publication types: Journal Article
Frequency, Risk Factors, and Clinical Outcomes of Late-Onset Atrial Flutter in Patients after Heart Transplantation.

S: atrial flutter (afl) is a common late-onset complication after heart transplantation (htx) and is associated with worse clinical outcomes.Methods: this study investigated the frequency, risk factors, and outcomes of late-onset post-transplant afl.We analyzed 639 adult patients undergoing htx at the heidelberg heart center between 1989 and 2019.Patients were stratified by diagnosis and type of late-onset post-transplant afl (>90 days after htx).Results: a total of 55 patients (8.6%) were diagnosed with late-onset post-transplant afl, 30 had typical afl (54.5%) and 25 had atypical afl (45.5%).Patients with afl were younger at htx (p = 0.028), received more biatrial anastomosis (p = 0.001), and presented with moderate or severe tricuspid regurgitation (56.4%).Typical afl was associated with graft rejection (p = 0.016), whereas atypical afl was associated with coronary artery disease (p = 0.028) and stent implantation (p = 0.042).Patients with atypical afl showed a higher all-cause 1-year mortality (p = 0.010) along with a higher rate of graft failure after diagnosis of afl (p = 0.023).Recurrence of afl was high (83.6%).Patients with catheter ablation after afl recurrence had a higher 1-year freedom from afl (p = 0.003).Conclusions: patients with late-onset post-transplant afl were younger at htx, received more biatrial anastomosis, and showed a higher rate of moderate or severe tricuspid regurgitation.Typical afl was associated with graft rejection, whereas atypical afl was associated with myocardial ischemia, graft failure, and mortality.Catheter ablation represents a viable option to avoid further episodes of late-onset afl after htx.

Journal: Journal of cardiovascular development and disease (2022)
Publication types: Journal Article
Cosmetics: What Do Bruneian Female Adults Believe?

S the study aimed to measure the level of attitudes and the current practices of the female community in brunei darussalam regarding the usage of cosmetics.Methods an online survey was conducted using a non-probabilistic snowball sampling approach via the social media channels whats app and instagram.The inclusion criteria were female bruneian citizens or permanent residents, aged between 18 and 65 years old, who can understand english or malay, and use cosmetic products at least once a day.Results a total of 445 participants responded to the online survey.Most of the participants agreed that the use of cosmetic products improves one's physical appearance to the public (391, 87.8%) and also improves self-confidence (405, 91.1%).There were significant differences in monthly cosmetic product expenses and participants' attitudes about safe cosmetic use (p= 0.001).No significant changes in the individuals' attitudes based on their age or educational level were observed.Overall, the participants had a good level of cosmetic safety practice.Almost half of the participants use social media to obtain information regarding what cosmetics to use or purchase.Conclusion there is a medium to high level of attitude and a high level of practice regarding the safe use of cosmetics among bruneian female adults.Social media was the main source of information for the respondents, followed by friend circle and family members.

Journal: International journal of environmental research and public health (2022)
Publication types: Journal Article
Surfactant-Free Aqueous Dispersions of Shape- and Size-Controlled Zirconia Colloidal Nanocrystal Clusters with Enhanced Photocatalytic Activity.

Colloidal nanocrystal clusters (cncs) are formed by clustering nanocrystals into secondary structures, which represent a new class of materials and have attracted considerable attention, owing to their unique collective properties and novel functionalities achieved from the ensembles in addition to the properties of each individual subunit.Here, we design a simple route to prepare aqueous dispersions of highly stable zr o2cncs with tunable shape and size without modification.Zr o2cncs are composed of many zr o2nanocrystals each with a size of about 7 nm and possess a mesoporous structure.Both cube-like and star-like shapes of cncs can be achieved by using different alkaline sources, while the size of cncs can be adjusted by changing the hydrothermal time.The as-prepared aqueous dispersions of zr o2cncs display an enhanced photocatalytic activity in the degradation of rhodamine b (rh b), compared with zr o2nanodispersions.More interestingly, star-like zr o2cncs show better photocatalytic degradation properties than those of cube-like counterparts and even commercial p25.Furthermore, zr o2cncs are easily recycled and can be used for the degradation of a range of dye systems.

Journal: Langmuir : the ACS journal of surfaces and colloids (2019)
Publication types: Journal Article
Droplet evaporation in finite-size systems: Theoretical analysis and mesoscopic modeling.

The classical d^{2}-law states that the square of the droplet diameter decreases linearly with time during its evaporation process, i.e., d^{2}(t)=d_{0}^{2}-kt, where d_{0} is the droplet initial diameter and k is the evaporation constant.Though the law has been widely verified by experiments, considerable deviations are observed in many cases.In this work, a revised theoretical analysis of the single droplet evaporation in finite-size open systems is presented for both two-dimensional (2d) and 3d cases.Our analysis shows that the classical d^{2}-law is only applicable for 3d large systems (l≫d_{0}, l is the system size), while significant deviations occur for small (l≤5d_{0}) and/or 2d systems.Theoretical solution for the temperature field is also derived.Moreover, we discuss in detail the proper numerical implementation of droplet evaporation in finite-size open systems by the mesoscopic lattice boltzmann method (lbm).Taking into consideration shrinkage effects and an adaptive pressure boundary condition, droplet evaporation in finite-size 2d/3d systems with density ratio up to 328 within a wide parameter range (k=[0.003,0.18] in lattice units) is simulated, and remarkable agreement with the theoretical solution is achieved, in contrast to previous simulations.The present work provides insights into realistic droplet evaporation phenomena and their numerical modeling using diffuse-interface methods.

Journal: Physical review. E (2022)
Publication types: Journal Article
Natural Variation of Seed Tocopherol Composition in Diverse World Soybean Accessions from Maturity Group 0 to VI Grown in China.

Tocopherols are natural antioxidants that increase the stability of fat-containing foods and are well known for their health benefits.To investigate the variation in seed tocopherol composition of soybeans from different origins, 493 soybean accessions from different countries (china, usa, japan, and russia) belonging to 7 maturity groups (mg 0-vi) were grown in 2 locations (beijing and hainan provinces of china) for 2 years (2017 and 2018).The results showed that significant differences (p< 0.001) were observed among the accessions and origins for individual and total tocopherol contents.The total tocopherol content ranged from 118.92 μg g-1to 344.02 μg g-1.Accessions from the usa had the highest average concentration of γ- and total tocopherols (152.92 and 238.21 μg g-1, respectively), whereas a higher level of α-tocopherol (12.82 μg g-1) was observed in the russian accessions.The maturity group of the accession significantly (p< 0.001) influenced all tocopherol components, and higher levels of α-, γ-, and total tocopherols were observed in early maturing accessions, while late-maturing accessions exhibited higher levels of δ-tocopherol.The inclination of tocopherol concentrations with various mgs provided further evidence of the significance of mg in soybean breeding for seed tocopherol components.Furthermore, the correlation between the seed tocopherol components and geographical factors revealed that α-, γ-, and total tocopherols had significant positive correlations with latitude, while δ-tocopherol showed an opposite trend.The elite accessions with high and stable tocopherol concentrations determined could be used to develop functional foods, industrial materials, and breeding lines to improve tocopherol composition in soybean seeds.

Journal: Plants (Basel, Switzerland) (2022)
Publication types: Journal Article
The global prevalence of depression, suicide ideation, and attempts in the military forces: a systematic review and Meta-analysis of cross sectional studies.

Given the wide range of depressive disorders, suicidal ideation and suicide attempts in various military studies around the world, determining the exact prevalence of these disorders in line with health planning as well as care and treatment service designing for military forces can be useful.The aim of the present meta-analysis was to determine the pooled prevalence of depressive disorders, suicide thoughts, and attempts in the military.Methods the present systematic review and meta-analysis study was performed based on prisma criteria in 5 steps of the search strategy, screening and selection of articles, data extraction, evaluation of article quality and meta-analysis.International databases (pub med (medline), scopus, web of science, embase (elsevier), psyc info (ovid), cochrane central (ovid)) were searched using related keywords extracted from mesh and emtree.After screening and final selection of articles, data were extracted and qualitative evaluation was performed using the nos checklist.Results the results of meta-analysis showed that the prevalence of depression in active military forces and veterans was 23% (%95 ci: 20-26%) and 20% (%95 ci: 18-22%), respectively.In addition, the prevalence of suicidal ideation and attempts in the military was 11% (%95 ci: 10-13%) and 11% (%95 ci: 9-13%), respectively.The prevalence of suicide ideation and attempts in drug-using military was 18% (%95 ci: 7-33%) and 30% (%95 ci: 23-36%), respectively.The prevalence of suicidal ideation and attempts in military consuming alcohol were 9% (%95 ci: 4-13%) and 8% (%95 ci: 7-10%), respectively.In militaries with aids / hiv, the prevalence of suicide attempts was 5% (%95 ci: 4-8%).Conclusion therefore, it is necessary to develop and design training and intervention programs in order to increase the awareness of the military, especially veterans, to prevent the occurrence of suicide and depression.

Journal: BMC psychiatry (2021)
Publication types: Journal Article;Meta-Analysis;Systematic Review
Navigating the digital divide: providing services to people with serious mental illness in a community setting during COVID-19.

Community mental healthcare around the world has been strained as people need more help and experience more barriers to access due to covid-19.The rapid shift to telehealth services necessitated by the pandemic has made these difficulties even more pronounced.While this transition presented challenges for nearly every healthcare system, it has proven especially difficult for low resource settings such as community health centers.This article is a critical observational study of the care transformation of a state-funded safety net psychiatric system responding to the clinical needs of patients during the covid-19 pandemic.By discussing the challenges, opportunities, and creative solutions for staff and patients, the article highlights the new importance of technology and adaptability in clinical care and outlines clear recommendations to ensure vulnerable populations do not fall into the "digital divide."

Journal: SN social sciences (2022)
Publication types: Journal Article
Association Between MTHFR Gene Common Variants, Serum Homocysteine, and Risk of Early-Onset Coronary Artery Disease: A Case-Control Study.

The common variants of the methylenetetrahydrofolate reductase (mthfr) gene are related to the activity of the mthfr enzyme and the concentrations of blood homocysteine (hcy).This study was designed to investigate the associations of mthfr in chinese populations with early-onset coronary artery disease (eocad).The two common variants of the mthfr gene were genotyped in 875 eocad patients and 956 controls using pcr, followed by direct sequencing of the pcr product.Serum levels of hcy were measured using an automatic biochemistry analyzer.A significant association between the mthfr-677c/t variant and the risk of eocad was detected in cc versus tt (odds ratio (or) 1.456, 95% confidence interval (ci) 1.120-1.892), dominant genetic model (or 1.266, 95% ci 1.027-1.546), and recessive genetic model (or 1.306, 95% ci 1.040-1.639).Hcy was most abundant in tt genotype (18.31 ± 7.22 μmol/l), least abundant in cc genotype (11.37 ± 5.23 μmol/l), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 μmol/l).Elevated serum hcy levels were an independent risk factor for eocad (oradjust1.431, 95% ci 1.135-1.763).Our findings indicated that the t allele of -677c/t mthfr variant predisposes to high levels of hcy, and that the t allele is an important risk factor for eocad in the chinese population.

Journal: Biochemical genetics (2020)
Publication types: Journal Article
An Improved Impact Ratio for Identifying Critical Process Parameters in Pharmaceutical Manufacturing Processes.

The identification of critical process parameters in biologics and small molecule process development is a key element of quality by design.The objectivity and consistency of procedures to identify critical process parameters can be improved with the use of impact ratios.Impact ratios quantify a process parameter's practical effect on a critical quality attribute relative to the critical quality attribute's acceptance limits.If the impact ratio is large, i.e., exceeds a predefined impact ratio threshold, the recommendation is to classify the process parameter as a critical process parameter.This article introduces an improved and mathematically well-defined impact ratio.Benefits of this impact ratio are a consistent interpretation for many scenarios commonly encountered in practice, high suitability to automation, and the possibility of standardizing on a single impact ratio definition for pharmaceutical manufacturing.

Journal: PDA journal of pharmaceutical science and technology (2022)
Publication types: Journal Article
Which psychosocial factors are associated with return to sport following concussion? A systematic review.

Psychosocial factors predict recurrent injury and return to preinjury level of performance following orthopedic injury but are poorly understood following concussion.Current management protocols prioritize physical measures of recovery.Therefore, the objective of this study was to describe the psychosocial factors associated with return to sport (rts) and how they are measured in athletes who sustained a concussion.Methods medline, embase, apa psyc info, cinahl, and sportdiscus were searched through february 2, 2021.Eligible studies included original peer-reviewed publications describing psychosocial factors associated with rts following a diagnosed concussion.The primary outcome was scales or measures employed and/or key thematic concepts.Results of the 3615 studies identified, 10 quantitative cohort studies (oxford centre for evidence-based medicine level-3) representing 2032 athletes (85% male; high-school and collegiate collision/contact athletes) and 4 qualitative studies representing 66 athletes (74% male; 70% american football; aged 9-28 years) were included.We identified 3 overarching themes and 10 outcome measures related to psychosocial factors associated with rts following concussion: (a) fear (e.g, of recurrent concussion, of rts, of losing playing status); (b) emotional factors (e.g, depression, anxiety, perceived stress, mental health, disturbance mood); and (c) contextual factors (e.g, social support, pressure, sense of identity).Conclusion although current medical clearance decisions prioritize physical measures of recovery, evidence suggests diverse psychosocial factors influence rts following concussion.It remains unclear which psychosocial factors contribute to a successful rts, including the influence of sex/gender and age.Future studies should evaluate the association of psychological readiness with physical measures of recovery at medical clearance, preinjury level of performance, and risk of recurrent concussion to support rts clinical decision-making.

Journal: Journal of sport and health science (2022)
Publication types: Journal Article;Review;Systematic Review
Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects.

Glipizide is a second-generation sulfonylurea antidiabetic drug.It is principally metabolized to inactive metabolites by genetically polymorphic cyp2c9 enzyme.In this study, we investigated the effects of cyp2c9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide.Twenty-four healthy korean volunteers (11 subjects with cyp2c9*1/*1, 8 subjects with cyp2c9*1/*3, and 5 subjects with cyp2c9*1/*13) were recruited for this study.They were administered a single oral dose of glipizide 5 mg.The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters.The results represented that cyp2c9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide.In subjects with cyp2c9*1/*3 and cyp2c9*1/*13 genotypes, the mean auc0-∞were increased by 44.8% and 58.2%, respectively (both p < 0.001), compared to those of subjects with cyp2c9*1/*1 genotype, while effects of glipizide on plasma glucose and insulin levels were not significantly different between cyp2c9 genotype groups.In conclusion, individuals carrying the defective cyp2c9*3 and cyp2c9*13 alleles have markedly elevated plasma concentrations of glipizide compared with cyp2c9*1/*1 wild-type.

Journal: Archives of pharmacal research (2022)
Publication types: Journal Article
Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers.

Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions.Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine.Moreover, the dutch pharmacogenomics working group (dpwg) states that cyp2d6 phenotype is not related to olanzapine response or side effects.Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g.Abcb1, abcc2, slc22a1), receptors (e.g.Drd2, htr2c), and enzymes (e.g.Ugt, cyp and comt), in a cohort of healthy volunteers.Polymorphisms in cyp2c9, slc22a1, abcb1, abcc2, and apoc3 were related to olanzapine pharmacokinetic variability.The incidence of adverse reactions was related to several genes: palpitations to abcb1 and slc22a1, asthenia to abcb1, somnolence to drd2 and abcb1, and dizziness to cyp2c9.However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2021)
Publication types: Journal Article;Observational Study