bluuebunny/crossref_metadata_2025 huggingface dataset:
B cell‐intrinsic changes with age do not impact antibody‐secreting cell formation but delay B cell participation in the germinal centre reaction
Authors: Lee Jia Le , Fra‐Bido Sigrid C. , Burton Alice R. , Innocentin Silvia , Hill Danika L. , Linterman Michelle A.
Published: August 2022

Vaccines typically protect against (re)infections by generating pathogen‐neutralising antibodies. However, as we age, antibody‐secreting cell formation and vaccine‐induced antibody titres are reduced. Antibody‐secreting plasma cells differentiate from B cells either early post‐vaccination through the extrafollicular response or from the germinal centre (GC) reaction, which generates long‐lived antibody‐secreting cells. As the formation of both the extrafollicular antibody response and the GC requires the interaction of multiple cell types, the impaired antibody response in ageing could be caused by B cell intrinsic or extrinsic factors, or a combination of the two. Here, we show that B cells from older people do not have intrinsic defects in their proliferation and differentiation into antibody‐secreting cells in vitro compared to those from the younger donors. However, adoptive transfer of B cells from aged mice to young recipient mice showed that differentiation into extrafollicular plasma cells was favoured at the expense of B cells entering the GC during the early stages of GC formation. In contrast, by the peak of the GC response, GC B cells derived from the donor cells of aged mice had expanded to the same extent as those from the younger donors. This indicates that age‐related intrinsic B cell changes delay the GC response but are not responsible for the impaired antibody‐secreting response or smaller peak GC response in ageing. Collectively, this study shows that B cells from aged individuals are not intrinsically defective in responding to stimulation and becoming antibody‐secreting cells, implicating B cell‐extrinsic factors as the primary cause of age‐associated impairment in the humoral immunity.
Ageing‐related effects of dye penetration in the apical 5 mm mesiobuccal and mesial roots of molars
Authors: Hahn Chin‐Lo , Sherman Jordan , Hanford Kathryn
Published: August 2022

This study examined how the tubular permeability in the apical 5 mm of mesial roots was affected by age, direction, distance from root apex, canal shape and canal number. Twenty mesiobuccal/mesial roots of maxillary/mandibular molars from three age groups (<30, 30–60, >60 years) were prepared. Maximal dye penetration in buccal, lingual, mesial and distal directions was measured at 1‐mm segment depth and analysed statistically. The <30 years group, when comparing to the >60 years group, had significantly deeper dye penetration in buccal and lingual directions. The permeability in proximal directions was not affected by either age or canal number. In the >60 years group, neither direction, segment depth nor canal number significantly impacted the permeability. However, these parameters significantly impacted samples younger than 60 years. Effective removal of infected root canal dentine would depend on age and its related preferred direction, distance from root apex and canal number.
Use of statins after liver transplantation is associated with improved survival: results of a nationwide study
Authors: Becchetti Chiara , Dirchwolf Melisa , Schropp Jonas , Magini Giulia , Müllhaupt Beat , Immer Franz , Dufour Jean‐François , Banz Vanessa , Berzigotti Annalisa , Bosch Jaume ,   Swiss Transplant Cohort Study
Published: August 2022

Background

There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors.

Aim

To analyse the association between statin exposure and recipient and graft survival.

Methods

We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years.

Results

We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow‐up, 141 patients died; there were 40 re‐LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12–0.98; p = 0.047), as well as a significant reduction of re‐LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85–1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01–0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20–0.93; p = 0.032).

Conclusions

Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated.
A multicenter survey of effects and challenges of an 8K ultra‐high‐definition endoscopy system compared to existing endoscopy systems for endoscopic surgery
Authors: Kono Yohei , Inomata Masafumi , Sumi Yasuo , Ohigashi Seiji , Ieiri Satoshi , Shin Toshitaka , Shinohara Toshihiko , Abe Tetsuya , Osoegawa Atsushi , Fujisawa Masato , Mori Toshiyuki , Kitagawa Yuko , Kitano Seigo ,   the Forum of 8K Endoscopy Medical Application Forum
Published: August 2022

Introduction

8K ultra‐high‐definition (UHD) images enabling clearer recognition of anatomical structures could contribute to further development of surgical techniques and advanced applications in endoscopic surgery fields. This study aimed to clarify effects and challenges of endoscopic surgery with 8K UHD endoscopy compared to existing endoscopy systems.

Methods

In this multicenter, cross‐sectional, questionnaire survey, data were collected from surgical participants who newly used and observed 8K UHD endoscopy in patients undergoing surgery from February 2020 to February 2021. Survey items included sense of presence, reality, depth perception, visibility of tissue, eyestrain, and degree of satisfaction for operators and observers, and weight, operability, focus adjustment, physical fatigue, eyestrain, and satisfaction for camera assistants. Participants rated each 8K UHD endoscopic surgery on a one‐to‐five scale (definitively inferior, relatively inferior, equivalent, relatively superior, definitively superior) compared to the existing endoscopy system of each facility.

Results

Overall, questionnaire responses from 139 participants assessing 8K UHD endoscopic surgery were collected from surgeries performed in 46 patients. Respective ratings of operators and observers included sense of presence: “superior or relatively superior”, 97.8% and 91.5%; reality: “superior or relatively superior”, 76.1% and 72.3%; and visibility of tissue: “superior or relatively superior”, 93.5% and 87.2%. Weight was rated as “inferior or relatively inferior” by 73.9% of camera assistants and focus adjustment as “inferior” by 60.9% of them.

Conclusions

8K UHD endoscopic surgery enabled identification of surgical anatomies more clearly, provided a sense of presence and reality, and might improve educational effect. Technological development is expected to reduce the burden of camera assistants.
Testing Weak Nulls in Matched Observational Studies
Authors: Fogarty Colin B.
Published: August 2022

We develop sensitivity analyses for the sample average treatment effect in matched observational studies while allowing unit-level treatment effects to vary. The methods may be applied to studies using any optimal without-replacement matching algorithm. In contrast to randomized experiments and to paired observational studies, we show for general matched designs that over a large class of test statistics, any procedure bounding the worst-case expectation while allowing for arbitrary effect heterogeneity must be unnecessarily conservative if treatment effects are actually constant across individuals. We present a sensitivity analysis which bounds the worst-case expectation while allowing for effect heterogeneity, and illustrate why it is generally conservative if effects are constant. An alternative procedure is presented that is asymptotically sharp if treatment effects are constant, and that is valid for testing the sample average effect under additional restrictions which may be deemed benign by practitioners. Simulations demonstrate that this alternative procedure results in a valid sensitivity analysis for the weak null hypothesis under a host of reasonable data-generating processes. The procedures allow practitioners to assess robustness of estimated sample average treatment effects to hidden bias while allowing for effect heterogeneity in matched observational studies.
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

The 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

Introduction

High 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.

Methods

This 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.

Results

The 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).

Conclusion

Serum 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

Objective

Hypothalamic 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.

Design

This study is a single‐centre, retrospective study that covers patients from 1989 to 2019.

Patients

We included 40 children and adolescents with hypothalamic dysfunction from our medical centre in Beijing, China.

Results

Intracranial 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.

Conclusions

Intracranial 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

Background

Age‐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.

Methods

We 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.

Results

Six (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.

Conclusion

Only 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

Enhancing 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

A 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

Perianal 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

Real‐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

Aims

To 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.

Methods

We 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.

Results

Patients 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.

Conclusions

The 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

Binding 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

Aim

To 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.

Methodology

Fluorescence 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.

Results

A 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).

Conclusion

MiR‐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

Group‐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

Introduction

Pulmonary 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.

Methods

In 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.

Results

EDEL 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.).

Conclusion

Incidence 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.
A survey of clinical physician's perceptions of stigma and advocacy in patients with type 2 diabetes in Kanagawa, Japan
Authors: Matsuzawa Yoko , Azuma Kosuke , Sawa Tasuku , Ono Yoshiaki , Hamada Yoshiro , Matsuba Ikuro , Kanamori Akira
Published: August 2022

Aims/Introduction

To investigate the recognition status of stigma/advocacy in patients with type 2 diabetes in clinical practice settings.

Method

A questionnaire survey on stigma/advocacy of patients with diabetes was carried out for members of the Kanagawa Physicians Association in July 2021.

Results

The respondents consisted of 33 (16.6%) physicians specializing in diabetes (the D group) and 166 (83.4%) non‐specialists (the ND group). 100% of the D group and 48.8% of the ND group knew that patients may be prejudiced or discriminated against because of diabetes. In the question of whether they know the terms ‘stigma’ and ‘advocacy’, ‘know’ was 97.0% and 94.0% in the D group, compared with 45.8% and 36.7% in the ND group, respectively. 97.0% of the D group and 19.9% of the ND group know the advocacy activities of the Japanese Diabetes Society (JDS) and the Japan Association for Diabetes Education (JADEC). The specific contents of the stigma were often unknown or never experienced in the ND group. A free description of the strategy for reducing or eliminating stigma was analyzed by text mining. ‘Giving consideration to the patients' feelings’, ‘Commitment to the problem’, and ‘Dialogue’ were frequent, and there was no significant difference between the two groups.

Conclusions

The clinician's understanding of stigma/advocacy associated with having diabetes was insufficient, and activities that alert clinicians to stigma/advocacy, especially those in the ND group, was a theme to be addressed. More awareness‐raising activities for stigma/advocacy will lead to better treatment and a better quality of life for patients with diabetes.
Year‐long effects of COVID‐19 restrictions on glycemic control and body composition in patients with glucose intolerance in Japan: A single‐center retrospective study
Authors: Tsukaguchi Ryo , Murakami Takaaki , Yoshiji Satoshi , Shide Kenichiro , Fujita Yoshihito , Ogura Masahito , Inagaki Nobuya
Published: August 2022

Aims/Instruction

During the coronavirus disease 2019 (COVID‐19) pandemic, the lockdowns in Europe raised concerns about negative effects on glycemic control and body composition in patients with diabetes. In Japan, voluntary‐based restrictions were imposed as the declaration of a state of emergency (DSE), whose metabolic consequences have not been fully investigated. We carried out a single‐center retrospective study to evaluate changes in glycemic control and body composition in outpatients with glucose intolerance after the DSE.

Materials and Methods

We enrolled outpatients with glucose intolerance: (i) for whom longitudinal data about body composition were available; (ii) who participated in dietary follow up with nutritionists; and (iii) whose laboratory data included glycated hemoglobin (HbA1c) levels before and after the DSE.

Results

Among 415 patients, we found no significant changes in HbA1c overall after the DSE. Bodyweight and fat mass increased significantly, whereas skeletal mass decreased significantly. HbA1c changes after the DSE were significantly correlated with changes in bodyweight and fat mass. In 128 patients whose HbA1c levels increased ≥0.3%, changes in bodyweight and fat mass were significantly larger than those in the other 287 patients. With regard to lifestyle changes, increased snacking was likely to worsen glycemic control (odds ratio 1.76, P = 0.036).

Conclusions

COVID‐19 restrictions in Japan had unfavorable metabolic consequences for patients with glucose intolerance, highlighted by increased bodyweight and body fat, and decreased skeletal muscle. In addition, lifestyle changes, such as increased snacking, might worsen glycemic control. Clinical attention and interventions are required to prevent such metabolic changes.
Identification of lncRNA expression profiles in pediatric localized scleroderma
Authors: Gong Yinv , Liu Haimei , Li Guomin , Sun Li
Published: August 2022

The role and potential molecular mechanism of inflammatory cells in pediatric localized scleroderma are poorly investigated. In this study, we first investigated the profiling of inflammatory cells in skin samples from pediatric localized scleroderma. Among them, CD4+ T‐cells were up‐regulated. Co‐culture dermal fibroblasts with CD4+ T‐cells promoted fibrosis of fibroblasts. Candidate lncRNAs were further explored by lncRNAs‐seq between the normal skin tissues and pediatric localized scleroderma tissues, and the lncRNAs‐seq between fibroblasts co‐cultured with CD4+ T lymphocytes and control fibroblasts. By comparing the two datasets, we identified eight up‐regulated and three down‐regulated lncRNAs, which were the potential lncRNAs for the phenotype of pediatric localized scleroderma. Here, we identified the CD4+ T‐cells infiltration in pediatric localized scleroderma and potential lncRNAs for the treatment of pediatric localized scleroderma.
The association of three doses of theBNT162b2 mRNAvaccine with abnormal bleeding and an irregular menstrual cycle among premenopausal females: A single institute observation study
Authors: Namiki Takahiro , Komine‐Aizawa Shihoko , Takada Kazuhide , Takano Chika , Trinh Quang Duy , Hayakawa Satoshi
Published: August 2022

Background

The COVID‐19 vaccine is effective in preventing severe cases of COVID‐19. For women, gynecological adverse events, such as menstrual irregularities and irregular bleeding, could be a concern after COVID‐19 vaccination. In this study, we investigated gynecological adverse events in the vaccinated Japanese female population.

Methods

We conducted a survey‐based study with health‐care workers, including medical doctors and nurses, medical coworkers, and medical university faculty, staff, and students, at a single medical school and affiliated hospital in Japan. We used McNemar's test and network analysis.

Results

Overall, we obtained 819 responses, and 424 were from females. After the exclusion of contradictory answers, 309 surveys were finally considered appropriate for the analysis. The frequencies of abnormal bleeding were 0.6%, 1.0%, and 3.0% for the first, second, and third doses, respectively. An irregular menstrual cycle was more common than abnormal bleeding: 1.9%, 4.9%, and 6.6% for the first, second, and third doses, respectively. Network analysis revealed that abnormal bleeding and an irregular menstrual cycle were not associated with other adverse reactions.

Conclusion

The present study showed that the effects of COVID‐19 vaccination on menstruation seem limited.
The trueness of scans using one intraoral scanner in different partially edentulous conditions
Authors: Majeed‐Saidan Ahmad , Dutra Vinicius , Levon John A. , Chu Tien‐Min G. , Morton Dean , Alfaraj Amal , Lin Wei‐Shao
Published: August 2022

Purpose

To investigate the trueness of intraoral scanning in 8 commonly seen partially edentulous conditions.

Materials and methods

A maxillary dentoform was modified into the 8 commonly seen partially edentulous conditions. Each modification was scanned with a laboratory desktop scanner. Each modification was then scanned 10 times (n = 10) with an intraoral scanner. All scans were exported as STL files and then imported into a surface matching software using the best‐fit alignment method. The dimensional differences between the study STL files from the intraoral scanner were compared to the corresponding reference STL files. The measurements were calculated as the root mean square (RMS) and defined as the trueness of the intraoral scans. In addition to the RMS values, qualitative assessments were completed on the color maps. The color maps produced by the surface matching software were used to visualize the areas of deviation between scans from the intraoral scanner and their corresponding reference files. One‐way analysis of variance (ANOVA), followed by pair‐wise comparisons using Fisher's Protected Least Significant Difference were utilized to compare the differences between the groups in RMS values (α = 0.05).

Results

Partially edentulous condition significantly affected the trueness of the intraoral scans. Group 8 (Class IV) had significantly lower RMS (0.1878 ± 0.0455 mm) than all other groups (p < 0.001). Group 2 (Class II) and Group 7 (Class III modification I) are not significantly different from each other (Group 2: 0.5758 ± 0.0300 mm; Group 7: 0.5602 ± 0.0231 mm, p = 0.571), while they both had significantly higher RMS than all other groups (p < 0.001). The remaining groups showed the RMS values were within the range of 0.3001 ± 0.0891 mm (Group 6 – Class III with Long Edentulous Span) and 0.4541 ± 0.1039 mm (Group 1 – Class I).

Conclusion

Different partially edentulous conditions affected the trueness of the scans generated from the selected intraoral scanner. Class IV edentulous condition had the highest intraoral scan trueness. It is unknown if RMS values are clinically significant, and the validity of using intraoral scans directly for PRDP fabrication will need further studies.
Staff knowledge, attitudes and practices regarding glycaemic management in adult intensive care units: A national survey
Authors: Huang Miao , Yang Ruiqi , Zhang Chuanlai , Gan Xiuni
Published: August 2022

Background

Hyperglycaemia is common in critically ill adult patients. Many studies have identified the content, methods, and effects of glycaemic control but have not explored the effects of knowledge, attitudes, and practices (KAP) on glycaemic control in critically ill adults. Various factors also influence the KAP of intensive care unit (ICU) staff.

Aims

To assess KAP regarding glucose management for critically ill adults among nurses and medical professionals and identify the factors that influence their KAP in ICUs.

Methods

A multicentre cross‐sectional survey.

Results

In total, 403/459 (response rate: 87.8%) participants from ICUs in nine tertiary hospitals in China participated in this study, 82.4% of whom were female and 93.4% of whom were nurses. The mean work experience was 8.88 years, and the mean critical care experience was 6.59 years. The scoring rate for the three dimensions of knowledge, attitudes, and practices were 82.35%, 87.69%, and 76%, respectively. We did not find any other factors affecting the KAP scores except for the level of knowledge awareness (p < 0.001), awareness of the importance (p < 0.001), and training for glucose control (p = 0.004).

Conclusion

ICU staff KAP regarding glycaemic control in critically ill adults among ICU professionals were acceptable in China. However, ICU professionals' current knowledge regarding nutrition, glucose variability, and skills related to glucose management could be improved.

Relevance to Clinical Practice

ICU educators should provide more skills‐related training for healthcare professionals in the glycaemic management of critically ill adults. Moreover, the process of managing blood glucose in adult ICU patients is a collaborative, multidisciplinary team effort, with monitoring and feedback required during implementation.
Do variants in the coding regions of FOXP2, a gene implicated in speech disorder, confer a risk for congenital amusia?
Authors: Peretz Isabelle , Ross Jay , Bourassa Cynthia V. , Perreault Louis‐Philippe Lemieux , Dion Patrick A. , Weiss Michael W. , Felezeu Mihaela , Rouleau Guy A. , Dubé Marie‐Pierre
Published: August 2022

Congenital amusia is a lifelong disorder that compromises the normal development of musical abilities in 1.5–4% of the general population. There is a substantial genetic contribution to congenital amusia, and it bears similarities to neurodevelopmental disorders of language. Here, we examine the extent to which variants in the forkhead box P2 gene (FOXP2)—the first gene to be identified as causal in developmental speech deficits—are associated with the amusic trait. Using a cohort of 49 individuals with amusia, of which 27 were unrelated, the role of FOXP2 variants in amusia was evaluated. Fourteen variants were examined in the cohort. None segregated with the amusic trait among participants for whom family information was available; nor were they predicted to be deleterious to protein function. Thus, variants in FOXP2 are not likely to cause amusia. Implications for ongoing debates about the distinction between musicality and language are discussed.
Posterior Decompression and Fusion with Vertical Pressure Procedure in the Treatment of Multilevel Cervical OPLL with Kyphotic Deformity
Authors: Li Cheng , Mei Yunli , Li Lei , Li Zeqing , Huang Shuai
Published: August 2022

Objective

To report the outcomes and feasibility of a new technique to change K‐line (−) to K‐line (+) via only a posterior approach to treat multilevel non‐continuous cervical ossification of the posterior longitudinal ligament (C‐OPLL) with kyphotic deformity.

Methods

In this study, 17 consecutive cases of patients who underwent vertical pressure procedure (VP) combined with posterior cervical single‐open‐door laminoplasty and instrumented fusion from January 1, 2017 to December 31, 2019 were enrolled. The following radiographic parameters: C2‐C7 Cobb angle, local Cobb angle, extent of OPLL, and the distance from OPLL to the K‐line(DK) were measured and analyzed. Clinically, the JOA score, VAS‐N and VAS‐A, NDI, and complications were collected from medical records to evaluate the clinical outcomes.

Results

All 17 cases shifted from K‐line (−) to K‐line (+).Comparing the preoperative images to the final follow‐up images, the mean C2‐7 Cobb angle changed from −6.94° ± 8.30° to 8.18° ± 4.43°, and the local Cobb angle altered from −9.12° ± 8.68° to 6.65° ± 6.11°. The mean DK increased from −2.64 ± 1.52 mm to 3.09 ± 2.19 mm. One patient showed C5 palsy and recovered within 3 months. The mean JOA score increased from 8.88 ± 2.11 to 14.71 ± 1.36. The average NDI decreased from 20.65 ± 7.80 to 8.94 ± 4.93. The mean VAS‐N and VAS‐A decreased from 3.44 ± 1.80 and 4.69 ± 1.97 to 1.25 ± 0.86 and 1.38 ± 1.16. All patients were followed up for at least 1 year.

Conclusion

A new technique added to posterior decompression and fusion (PDF), the vertical pressure procedure effectively corrects K‐line (−) to K‐line (+) and avoids the shortcomings of conventional anterior decompression and fusion (ADF) as well as PDF to provide a relatively safe and adequate decompression, cervical realignment. It pronounced satisfactory clinical outcome for extensive non‐continuous OPLL with kyphotic deformity even though OPLL remains ventral to the spinal cord.