bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐Candida, docking studies, and in vitro metabolism‐mediated cytotoxicity evaluation of Eugenol derivatives
Authors: Dutra Jessyca Aparecida Paes , Maximino Sarah Canal , Gonçalves Rita de Cássia Ribeiro , Morais Pedro Alves Bezerra , de Lima Silva William Cezar , Rodrigues Ricardo Pereira , Neto Álvaro Cunha , Júnior Valdemar Lacerda , de Souza Borges Warley , Kitagawa Rodrigo Rezende 
Published: August 2022

AbstractThe high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti‐Candida potential and the cytotoxic profile of eugenol derivatives. Anti‐Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol‐14‐α‐demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti‐Candida activity against both strains with MIC ranging from 50 to 100 μg ml−1. SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol‐14‐α‐demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti‐Candida agent prototypes.
Food antigen consumption and disease activity affect food‐specific IgG4 levels in patients with eosinophilic esophagitis (EoE)
Authors: McGowan Emily C. , Medernach Jonathan , Keshavarz Behnam , Workman Lisa J. , Li Rung‐chi , Barnes Barrett H. , Sauer Bryan , Wilson Jeffrey M. , Platts‐Mills Thomas A. E. 
Published: August 2022

AbstractIntroductionHigh levels of serum food‐specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics.MethodsThis was a case–control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE‐negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels.ResultsThe analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p = .30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p = .24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p = .01) and the presence of sIgE to milk (OR 4.23; p = .008).ConclusionSerum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non‐EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.
The clinical and metabolic characteristics of children and adolescents with hypothalamic dysfunction: A single‐centre study from China
Authors: Ke Xiaoan , Yuan Xianxian , Zhang Yuelun , Wang Linjie , Feng Feng , Yao Yong , You Hui , Yang Hongbo , Lu Lin , Chen Shi , Duan Lian , Gong Fengying , Pan Hui , Zhu Huijuan 
Published: August 2022

AbstractObjectiveHypothalamic dysfunction is characterized by complex aetiologies, multiple forms of onset and various clinical symptoms. This study aims to explore the clinical and metabolic characteristics of hypothalamic dysfunction in Chinese children and adolescents.DesignThis study is a single‐centre, retrospective study that covers patients from 1989 to 2019.PatientsWe included 40 children and adolescents with hypothalamic dysfunction from our medical centre in Beijing, China.ResultsIntracranial tumour (37.5%) was the most common aetiology of children and adolescents with hypothalamic dysfunction, especially germ cell tumours, hypopituitarism (82.5%), weight gain (72.5%) and central diabetes insipidus (70.0%) were the most common symptoms in these patients. Furthermore, serum alanine aminotransferase, aspartate aminotransferase, γ‐glutamyl transpeptidase, uric acid, total cholesterol, triglycerides and low‐density lipoprotein cholesterol was significantly higher in hypothalamic dysfunction patients than sex‐ and age‐matched controls and sex, age and body mass index (BMI)‐matched controls (all p < 0.05). However, albumin and high‐density lipoprotein cholesterol were lower (p< 0.05). Moreover, 95% (38/40) of the patients had metabolic diseases. In addition, the incidence of dyslipidaemia and hyperuricemia in children and adolescents with hypothalamic dysfunction was significantly higher than both sex‐ and age‐matched controls and sex‐, age‐ and BMI‐matched controls (both p < 0.05) as well.ConclusionsIntracranial tumour was the most common aetiology in children and adolescents with hypothalamic dysfunction. In addition, these patients presented a worse metabolic profile on average than healthy patients.
Associations between age‐related macular degeneration and sleep dysfunction: A systematic review
Authors: Sia Josh Tjunrong , Lee Ester P. X. , Cheung Chui Ming Gemmy , Fenwick Eva K. , Laude Augustinus , Ho Kam Chun , Fenner Beau J. , Wong Tien Y. , Milea Dan , Lamoureux Ecosse L. , Man Ryan E. K. , Najjar Raymond P. 
Published: August 2022

AbstractBackgroundAge‐related macular degeneration, a prevalent degenerative retinal disease, is associated with non‐visual and psychosocial impairments that may affect sleep. In this systematic review, we evaluated associations between age‐related macular degeneration (AMD) and sleep, highlighted knowledge gaps and provided evidence‐based recommendations to clinicians to enable holistic management of AMD patients.MethodsWe searched PubMed, Embase and the Cochrane Central registries for papers published before May 2022. Non‐English, qualitative studies and grey literature were excluded. Studies evaluating the association between AMD and sleep (including sleep disorders like insomnia and sleep apnea), and vice versa, were included. The quality of shortlisted studies was evaluated using the Newcastle Ottawa Scale.ResultsSix (two case–control studies, three longitudinal cohort studies and one cross‐sectional study) of 551 studies were included in this review. Four studies found that AMD was associated with increased rates of sleep apnea and poorer reported sleep quality, while five studies showed that patients with sleep apnea or insomnia were at higher risk of developing AMD. Associations between self‐reported sleep quantity and AMD were conflicting. No study evaluated the relationship between AMD and sleep using objective sleep assessment tools.ConclusionOnly a limited number of studies investigated associations between AMD and sleep. These studies suggest a bidirectional relationship between AMD and sleep dysfunction yet disagree on the relationship between sleep quantity and the likelihood of AMD. Additional studies, using objective characterisation of sleep in patients with AMD are required to confirm these findings.
How resilient were we in 2021? Results of a LinkedIn Survey including biomedical and pharmaceutical professionals using the Benatti Resiliency Model
Authors: Zheng Songmao , Venkatakrishnan Karthik , Kennedy Beth Benatti 
Published: August 2022

AbstractEnhancing resiliency should elevate innovation and efficiency in biomedical research and development (R&D); however, compared with other professions, data on practice of resilience is lacking. Using the Benatti Resiliency Model (5 anchors: Well‐Being, Self‐Awareness, Brand, Connection, and Innovation), we surveyed professionals, including those in biomedical and pharmaceutical R&D. A structured LinkedIn questionnaire (March 16–May 23, 2021), surveyed each model anchor using five categories. One hundred fifty‐eight participants (~6% student/trainee, 18%, 27%, and 49% in 1–5, 5–15 or >15 years post‐terminal degree) took the survey (90 in biomedical and pharmaceutical R&D). Over 50% chose “always”/“often” across questions, except external influence or engagement. The question with one of the lowest “always” scores (~15%) was “I get feedback on my influence and impact in my career” in Brand, highlighting areas for leadership development and coaching. In the anchor of Well‐being, nutrition and stress management also received some lowest “always” scores (~15% for both). Connection and Innovation scores trended slightly higher in biomedical and pharmaceutical R&D. No students/trainees chose “always” in Brand, indicating evolution of brand maturity over time. Self‐ and survey‐assessed resiliency scores were associated (rs = 0.37, p < 0.0001). Our survey yielded actionable insights on Resilience, including “best practices” through an open‐ended question for one thing most useful to boost resilience in the survey and is the first application of the Benatti Model for crowdsourced research.
Malignant myopericytoma: Case report and review of the literature
Authors: Eubanks Bianca N. , Hall Jacob R. , Hall Kelly H. , Buck Shannon P. , Wohltmann Wendi E. 
Published: August 2022

AbstractA 29‐year‐old male presented with a two‐week history of a tender lesion on his right thigh. The lesion was a 1.5 cm erythematous nodule with overlying hemorrhagic crust. Histopathologic examination of a biopsy specimen revealed a highly cellular neoplasm with irregular vesicular nuclei, prominent nucleoli, and scattered mitotic figures. The cells within the lesion were rounded, ovoid and spindle shaped cells with perivascular growth. The architecture and staining pattern of the lesion were most consistent with a diagnosis of malignant myopericytoma, an exceedingly rare malignancy.
Perianal Paget disease associated with non‐invasive colorectal adenoma
Authors: Zuo Zhibo , Wu Wanxin , Li Xin , Zhang Lin , Wang Jingyu , Guo Zhiqin , Hu Shaoqing , Zhang Qi 
Published: August 2022

AbstractPerianal skin Paget disease (PPD) is an unusual subtype of extramammary Paget disease, which is usually caused by a primary intraepithelial adnexal tumor and secondary spread from colorectal adenocarcinoma. The reports of secondary PPD associated with non‐invasive colorectal adenoma are rare. We report a rare case of non‐invasive colorectal‐adenoma‐associated PPD. In this case, the intraepithelial Paget cells of perianal skin manifested with colorectal phenotype by immunohistochemistry, and adjacent adenomas had high‐grade intraepithelial neoplasia but not invasion. Although this is a rare manifestation of PPD, understanding this phenomenon is important to prevent overdiagnosis and invasive overtreatment. Clinical management is variable and, therefore, close follow‐up examination is necessary.
Real‐world glycaemic outcomes in adult persons with type 1 diabetes using a real‐time continuous glucose monitor compared to an intermittently scanned glucose monitor: A retrospective observational study from the Canadian LMC diabetes registry (REAL‐CGM‐T1D)
Authors: Brown Ruth E. , Chu Lisa , Norman Gregory J. , Abitbol Alexander 
Published: August 2022

AbstractReal‐time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycaemic outcomes in people with T1D. The aim of this study was to compare real‐world glycaemic outcomes at 6–12 months in a propensity score matched cohort of CGM naïve adults with T1D who initiated a rtCGM or an isCGM. Among the matched rtCGM and isCGM cohorts (n = 143/cohort), rtCGM users had a significantly greater HbA1c benefit compared to isCGM users (adjusted difference, −3 mmol/mol [95% CI, −5 to −1]; −0.3% [95% CI, −0.5 to −0.1]; p = 0.01). There was a significantly greater lowering of HbA1c for rtCGM compared to isCGM when baseline HbA1c was <69 mmol/mol (8.5%) (adjusted difference, −4 mmol/mol [95% CI, −7 mmol/mol to −2 mmol/mol]; −0.4% [95% CI, −0.6% to −0.2%]; p < 0.001), and in MDI users (adjusted difference, −3 mmol/mol [95% CI, −6 mmol/mol to −0 mmol/mol]; −0.3% [95% CI ‐0.5% to 0.0%], p = 0.04). The rtCGM cohort had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p = 0.03), lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p < 0.001) and lower glycaemic variability compared to the isCGM cohort. In this real‐world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6–12 months compared to isCGM, and significantly greater time in range, lower time below range and lower glycaemic variability, compared to a matched cohort of isCGM users.
Increased prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes and hypertension: The SWEET international database
Authors: Vazeou Andriani , Tittel Sascha R. , Kordonouri Olga , Birkebaek Niels H. , Iotova Violeta , Piccini Barbara , Seget Sebastian , Guness Pravesh Kumar , Maahs David M. , Stergiou George S. 
Published: August 2022

AbstractAimsTo investigate the prevalence of modifiable cardiovascular risk factors (CVRFs), including dyslipidaemia, obesity and high glycated haemoglobin (HbA1c) concentration, in patients with type 1 diabetes (T1D), and to evaluate their association with blood pressure (BP) categories.MethodsWe analysed 21 634 children and adolescents with T1D from the SWEET international database with office BP values assessed at a three or more visits within a year from 2010 to 2021. Participants were classified into a normotensive group, a group with elevated BP (90 to 94th percentile) or a hypertensive group (≥95th percentile), based on the median BP for the visits within the last treatment year. The prevalences of dyslipidaemia [cholesterol ≥ 5.18 mmol/L (200 mg/dL) and/or HDL cholesterol ≤ 1.036 mmol/L (40 mg/dL) and/or LDL cholesterol ≥ 2.59 mmol/L (100 mg/dL)], obesity (body mass index ≥2 standard deviation score) and elevated HbA1c [≥ 75 mmol/mol (9%)] were evaluated in patients within each BP group.ResultsPatients with hypertension/elevated BP had less favourable lipid profiles, and a higher prevalence of obesity and HbA1c ≥ 75 mmol/mol than normotensive patients. A total of 38.4% of hypertensive patients and 36.0% of those with elevated BP had one CVRF, 15.1% and 10.1%, respectively, had two CVRFs, and 2.3% and 0.8%, respectively, had three CVRFs. Patients with hypertension/elevated BP had a higher prevalence of one or more CVRFs versus normotensive patients (P < 0.001). Obesity was the CVRF most strongly related to hypertension. Girls had a higher prevalence of one or more CVRFs than boys. Similar results were found in patients aged ≥13 years with hypertension compared to those aged <13 years.ConclusionsThe prevalence of modifiable CVRFs is higher in children and adolescents with T1D who have elevated BP/hypertension than in those with normotension, suggesting that they are more vulnerable to future morbidity and mortality requiring early detection and intervention.
Competition in drug binding and … the race to equilibrium
Authors: Vauquelin Georges , Maes Dominique 
Published: August 2022

AbstractBinding kinetics has become a popular topic in pharmacology due to its potential contribution to the selectivity and duration of drug action. Yet, the overall kinetic aspects of complex binding mechanisms are still merely described in terms of elaborate algebraic equations. Interestingly, it has been recommended some 10 years ago to examine such mechanisms in terms of binding fluxes instead of the conventional rate constants. Alike the velocity of product formation in enzymology, those fluxes refer to the velocity by which one target species converts into another one. Novel binding flux‐based approaches are utilized to get a better visual insight into the “competition” between two drugs/ligands for a single target as well as between induced fit‐ and conformational selection pathways for a single ligand within a thermodynamic cycle. The present data were obtained by differential equation‐based simulations. Early on, the ligand‐binding steps “race” to equilibrium (i.e., when their forward and reverse fluxes are equal) at their individual pace. The overall/global equilibrium is only reached later on. For the competition association assays, this parting might produce a transient “overshoot” of one of the bound target species. A similar overshoot may also show up within a thermodynamic cycle and, at first glance, suggest that the induced fit pathway dominates. Yet, present findings show that under certain circumstances, it could rather be the other way round. Novel binding flux‐based approaches offer visually attractive insights into crucial aspects of “complex” binding mechanisms under non‐equilibrium conditions.
MicroRNA‐22 suppresses NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokine production by targeting the HIF‐1α and NLRP3 in human dental pulp fibroblasts
Authors: Jiang Wenkai , Sun Shukai , Wang Diya , Qiu Jun , Song Ya , Zhang Qianxia , He Wenxi , Song Bing , Zhang Yaqing , Wang Shengchao 
Published: August 2022

AbstractAimTo investigate the synergetic regulatory effect of miR‐22 on HIF‐1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis.MethodologyFluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR‐22‐3p, NLRP3 and HIF‐1α in human dental pulp tissues (HDPTs). The miR‐22 mimics and inhibitor or plasmid of NLRP3 or HIF‐1α were used to upregulate or downregulate miR‐22 or NLRP3 or HIF‐1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF‐1α, NLRP3, caspase‐1, IL‐1β and IL‐18 were determined by qRT‐PCR and western blotting, respectively. The release of IL‐1β and IL‐18 was analysed by ELISA. The significance of the differences between the experimental and control groups was determined by one‐way analysis of variance, p < .05 indicated statistical significance.ResultsA decrease in miR‐22 and an increase in HIF‐1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p < .05). In the normal HDPTs, miR‐22‐3p was extensively expressed in dental pulp cells. HIF‐1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR‐22‐3p, HIF‐1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF‐1α were direct targets of miR‐22 in HDPFs. The miR‐22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p < .05). In contrast, the miR‐22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p < .05).ConclusionMiR‐22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF‐1α. These results provide a novel function and mechanism of miR‐22‐HIF‐1α‐NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.
Is group‐buying price mechanism a good choice in the business‐to‐business system?
Authors: Guan Lei , Gu Wenxi , Niu Wenju , Zhang Lianmin 
Published: August 2022

AbstractGroup‐buying price mechanism is useful for online sales since the 1990s, yet it has not been widely applied in the business‐to‐business (B2B) environment. In this study, we consider a B2B supply chain with one supplier and multiple retailers. With our analytical model, we compare the supplier's profit under the flat price mechanism, individual quantity discount mechanism, and group‐buying price mechanism. The results show that when retailers are homogeneous, the individual quantity discount mechanism is the best choice for the supplier. In situations with heterogeneous retailers (i.e., a large retailer and multiple small retailers), the group‐buying price mechanism is the best choice when there is a moderate difference in market scale between retailers. However, the condition is quite strict. These findings also hold with a step‐wise price menu set by the supplier. Our conclusions explain why the group‐buying price mechanism is not widely used in the B2B environment and provide some advice for the supplier on how to choose suitable pricing mechanisms.
Esophageal safety in CLOSE‐guided 50 W high‐power‐short‐duration pulmonary vein isolation: The PREHEAT‐PVI‐registry
Authors: Francke Alexander , Naumann Gregor , Weidauer Marie‐Christin , Scharfe Frank , Schoen Steffen , Wunderlich Carsten , Christoph Marian 
Published: August 2022

AbstractIntroductionPulmonary vein isolation (PVI) using high‐power‐short‐duration (HPSD) radiofrequency ablation (RF) is emerging as the standard of care for treatment of atrial fibrillation (AF). While procedural short‐term to midterm efficacy and efficiency are very promising, this registry aims to investigate esopahgeal safety using an optimized ablation approach.MethodsIn a single‐center experience, 388 consecutive standardized first‐time AF ablation were performed using a CLOSE‐guided‐fixed‐50 W‐circumferential PVI and substrate modification without intraprocedural esophageal temperature measurement. Three hundred patients underwent postprocedural esophageal endoscopy to diagnose and grade endoscopically detected esophageal lesions (EDEL) and were included in the analysis.ResultsEDEL were detected in 35 of 300 patients (11.6%), 25 of 35 were low‐grade Kansas‐city‐classification (KCC) 1 lesions with fast healing tendencies. Six patients suffered KCC 2a lesions, 4 patients had KCC 2b lesions (1.3% of all patients). No esophageal perforation or fistula formation was observed. Patient baseline characteristics, especially patients age, gender, and body mass index did not influence EDEL incidence. Additional posterior box isolation did not increase the incidence of EDEL. In patients diagnosed with EDEL, mean catheter contact force during posterior wall ablation was higher (11.9 ± 1.8 vs. 14.7 ± 3 g, p < .001), mean RF duration was shorter (11.9 ± 1 vs. 10.7 ± 1.2 s, p < .001), while achieved ablation index was not different between groups (434 ± 4.9 vs. 433 ± 9.5, n.s.).ConclusionIncidence of EDEL after CLOSE‐guided‐50 W‐HPSD PVI is lower compared to historical cohorts using standard‐power RF settings. Catheter contact force during posterior HPSD ablation should not exceed 15 g.