bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal disproportion in girls with Turner syndrome and longitudinal change with growth‐promoting therapy
Authors: McVey Lindsey C. , Fletcher Alexander , Murtaza Mohammed , Donaldson Malcolm , Wong Sze Choong , Mason Avril
Published: January 2021

Objective

Short stature in Turner syndrome (TS) may be accompanied by skeletal disproportion. This retrospective study investigates growth and disproportion from early childhood to adult height.

Study design

Data were collected from 59 girls prior to growth hormone (rhGH) treatment and in 30 girls followed up longitudinally. Standard deviation scores (SDS) for height (Ht), sitting height (SH) and sub‐ischial leg length (LL) were compared and a disproportion score (SH SDS – LL SDS) calculated.

Results

In 59 girls, mean (SD) age 6.6 (2.1) years prior to rhGH treatment, LL SDS of −3.4 (1.1) was significantly lower than SH SDS of −1.2 (0.8) [p < .001]. In girls with Ht SDS < −2.0, disproportion score was > +2.0 in 27 (63%), cf eight (50%) with Ht SDS ≥ −2.0. For the longitudinal analysis, skeletal disproportion prior to rhGH was +2.4 (1.1) and +1.7 (1.0) on rhGH but prior to introduction of oestrogen [p < .001]. Disproportion at adult height was +1.1 (0.8), which was less marked than at the earlier time points [p < .001 for both comparisons]. Change in disproportion SDS over the first two years of rhGH predicted overall change in disproportion from baseline to adult height [R2 51.7%, p < .001].

Conclusion

TS is associated with skeletal disproportion, which is more severe in the shortest girls and present in only half of those with milder degrees of short stature. Growth‐promoting therapy may improve disproportion during both the childhood and pubertal phases of growth. Change in disproportion status two years after starting rhGH helps predict disproportion at adult height.
Snack time in kindergarten as a cultural practice—Implications for processes of subjectivation
Authors: Sieber Egger Anja , Unterweger Gisela , Kaiser Fabienne
Published: January 2021

This article explores subjectivation processes in eating situations in Swiss kindergartens. On the basis of a long‐term ethnographic study and against the backdrop of the public discourse on healthy food in schools it investigates how norms and rules are being translated, shaped and performed in daily practices of un/doing difference. This ethnomethodological approach is combined with Judith Butlers deconstructionist perspective of analysing local and institutional norms of recognisability. The findings show that eating situations are highly relevant for processes of subjectivation and also bear a high potential for conflicts regarding differing cultural norms around eating.
Fostering global dialogue: Conceptualisations of children's rights to participation and protection
Authors: Collins Tara M. , Rizzini Irene , Mayhew Amanda
Published: January 2021

The children's rights and child protection sectors are at a critical juncture: will they evolve to reflect and respond to changing conceptualisations in the 21st century or will they continue to reproduce 19th‐ and 20th‐century preoccupations with saving child victims? Informed by systematic reviews of the English‐ and Latin American academic literature in Spanish and Portuguese and key informant interviews with international stakeholders, this paper fosters global dialogue with some Global South and Global North perspectives about the interconnections of children's rights. It explores current conceptualisations of child participation and protection, and concludes that children's rights will only progress after recognition of limitations inherent to current conceptualisations.
Performance evaluation of stool DNA methylation tests in colorectal cancer screening: a systematic review and meta‐analysis
Authors: Gachabayov Mahir , Lebovics Edward , Rojas Aram , Felsenreich Daniel M , Latifi Rifat , Bergamaschi Roberto
Published: January 2021

Aim

There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID‐19 pandemic, there will be a wait‐list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta‐analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer.

Methods

The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian–Laird method with random‐effects model was utilized for meta‐analysis.

Results

Forty‐six studies totaling 16 149 patients were included in the meta‐analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%).

Conclusions

Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.
Gait features of dystonia in cerebral palsy
Authors: Aravamuthan Bhooma R , Ueda Keisuke , Miao Hanyang , Gilbert Laura , Smith Sarah E , Pearson Toni S
Published: January 2021

Aim

To determine the features cited by motor phenotyping experts when identifying dystonia in people with cerebral palsy (CP).

Method

Dystonia identification in CP, particularly when comorbid with spasticity, can be difficult. The dystonia diagnostic criterion standard remains subjective visual identification by expert consensus. For this qualitative study, we conducted an inductive thematic analysis of consensus‐building discussions between three pediatric movement disorder physicians as they identified the presence or absence of dystonia in gait videos of 40 participants with spastic CP and periventricular leukomalacia.

Results

Unanimous consensus about the presence or absence of dystonia was achieved for 34 out of 40 videos. Two main themes were present during consensus‐building discussions as videos were evaluated for dystonia: (1) unilateral leg or foot adduction that was variable over time, and (2) difficulty in identifying dystonia. Codes contributing to the first theme were more likely to be cited by a discussant when they felt dystonia was present (as opposed to absent) in a video (χ2test,p=0.004).

Discussion

These results describe the gait features cited by experts during consensus‐building discussion as they identify dystonia in ambulatory people with CP. Qualitative thematic analysis of these discussions could help codify the subjective process of dystonia diagnosis.
CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression
Authors: Lyu Pengfei , Zhai Zhensheng , Hao Zhengwen , Zhang Haoruo , He Jiefeng
Published: January 2021

Background

Circular RNAs (circRNAs) function as vital regulators in multifarious cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNA Wolf‐Hirschhorn syndrome candidate gene‐1 (circWHSC1) in HCC are barely known.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted for the levels of circWHSC1, miR‐142‐3p, miR‐421, miR‐665 and homeobox A1 (HOXA1) mRNA. Cell Counting Kit‐8 (CCK‐8) assay, colony formation assay and 5′‐ethynyl‐2′‐deoxyuridine (EdU) assay were used to evaluate cell proliferation ability. Transwell assay was adopted for cell migration and invasion. Western blot assay was employed for protein levels. RNA pull‐down assay, dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR‐142‐3p and circWHSC1 or HOXA1. Murine xenograft model assay was conducted for the role of circWHSC1 in vivo. The morphology of exosomes was observed by transmission electron microscopy (TEM).

Results

CircWHSC1 was elevated in HCC tissues and cells, and high level of circWHSC1 was associated with worse overall survival of HCC patients. Knockdown of circWHSC1 suppressed HCC cell proliferation and metastasis in vitro and restrained tumorigenesis in vivo. CircWHSC1 functioned as the sponge for miR‐142‐3p, which directly targeted HOXA1. Inhibition of miR‐142‐3p ameliorated the effects of circWHSC1 knockdown on HCC cell proliferation and metastasis. Moreover, miR‐142‐3p overexpression restrained the growth and motility of HCC cells, with HOXA1 elevation reversing the impacts. Additionally, circWHSC1 was increased in HCC patients’ serum and might be a diagnostic indicator for HCC.

Conclusion

CircWHSC1 played a tumour‐promoting role in HCC by elevating HOXA1 through sponging miR‐142‐3p.
Comparative analysis of corolla tube development across three closely related Mimulus species with different pollination syndromes
Authors: Gurung Vandana , Yuan Yao‐Wu , Diggle Pamela K.
Published: January 2021

Fusion of petals to form a corolla tube is considered a key innovation contributing to the diversification of many flowering plant lineages. Corolla tube length often varies dramatically among species and is a major determinant of pollinator preference. However, our understanding of the developmental dynamics underlying corolla tube length variation is very limited. Here we examined corolla tube growth in the Mimulus lewisii species complex, an emerging model system for studying the developmental genetics and evo‐devo of pollinator‐associated floral traits. We compared developmental and cellular processes associated with corolla tube length variation among the bee‐pollinated M. lewisii, the hummingbird‐pollinated Mimulus verbenaceus, and the self‐pollinated Mimulus parishii. We found that in all three species, cell size is non‐uniformly distributed along the mature tube, with the longest cells just distal to the stamen insertion site. Differences in corolla tube length among the three species are not associated with processes of organogenesis or early development but are associated with variation in multiple processes occurring later in development, including the location and duration of cell division and cell elongation. The tube growth curves of the small‐flowered M. parishii and large‐flowered M. lewisii are essentially indistinguishable, except that M. parishii tubes stop growing earlier at a smaller size, suggesting a critical role of heterochrony in the shift from outcrossing to selfing. These results not only highlight the developmental process associated with corolla tube variation among species but also provide a baseline reference for future developmental genetic analyses of mutants or transgenic plants with altered corolla tube morphology in this emerging model system.
Between locality variations in the seasonal patterns of dung beetles: the role of phenology in mitigating global warming effects
Authors: Cuesta Eva , Mingarro Mario , Lobo Jorge M.
Published: January 2021

1. Global warming may especially affect ectothermic insect species, making it necessary to forecast the capacity of these species to cope with climatic changes.

2. In this study, we use circular statistics to examine the seasonal plasticity of 32 dung beetle species in 17 localities of a mountain Iberian assemblage. We assume that the high variability between localities in the seasonal patterns for the same species suggests that seasonal plasticity could minimise the demographic effects of climate change on local populations.

3. Our results suggest that the populations of at least one‐third of the dung beetle species could partially adapt to the effects of climate change by modifying their phenological occurrence, and that the degree of concentration of the seasonal occurrences is generally maintained independently of the locality. However, we have not detected clear seasonal pattern variations or a clear effect of environmental temperature on seasonal variations in around two‐thirds of the studied species.

4. The dung beetle assemblages of this mountain region will experience deep changes in the future. Plasticity in seasonal patterns does not seem to be associated with species characteristics such as high‐rank taxonomic identity, body weight, or geographical distribution. Only the general functional character of species would have some explanatory power. Endophagic Aphodiidae dung beetle species would be more capable than hypophagic species in mitigating the effects of climate change by modifying their phenological traits, whereas that Scarabaeidae hypophagic species may cope better with these climatic changes without having to change their seasonal activities.
The effect of formal statistical courses attitudes on learning outcomes in a cohort of undergraduate dental students
Authors: Chen Fa , Hu Zhijian , Yan Lingjun , Lin Zheng , Liu Fengqiong , Lin Lisong , Qiu Yu , He Baochang
Published: January 2021

Introduction

Whilst statistical knowledge is essential for dental students' academic or professional careers, only a few studies have measured the attitudes of these students towards statistics courses. This study aimed to investigate the attitudes of a cohort of dental students towards a formal statistical course and explore the factors that are potentially related to these attitudes.

Methods

A survey was performed amongst dental students of 2017 entry at Fujian Medical University, China. The questionnaire covers three aspects: demographic characteristics, educational background and attitudes towards formal statistics courses.

Results

A total of 103 dental students enrolled for the survey, and the response rate was 100.0%. 44.7% of dental students had positive attitudes towards formal statistics courses with an overall average of 25.7 (SD = 2.2, out of 30). Students' computer skills, expectations of course achievement, attention in class and learning atmosphere of the class were significantly associated with the attitudes towards formal statistics courses. Moreover, students with positive attitudes experienced a greater improvement in the statistical cognition and application ability of statistical methods after the course than those with negative/neutral attitudes. Additionally, a positive correlation was observed between students' attitudes and achievement in the examination.

Conclusion

These results suggest that attitudes are critical to the learning effectiveness in formal statistics courses amongst undergraduate dental students. All the educators involved should monitor the students' attitudes in the teaching process and make effective interventions to improve students' attitudes towards formal statistics courses.
Xenophobia, the Unconscious, the Public Sphere and Brexit
Authors: Starkey Ken , Holstein Jeannie , Tempest Sue
Published: January 2021

We examine xenophobia from the perspective of the unconscious of individuals, groups and nations, emphasizing the role of fantasy, and arguing that some leaders use xenophobic discourse to exploit fantasies arising from emotions such as anxiety, fear and anger. We discuss this in the context of the public sphere as conceptualized by Habermas. We illustrate this with reference to an analysis of the psychic life of ‘Brexit’, the UK decision to exit the European Union in 2016, arguing that Brexit was one expression of the unconscious life of a nation. We contribute to our understanding of xenophobia and the role of psychodynamic forces within the public sphere by highlighting the key role of the unconscious and its ability to be influenced by leaders. We conclude by reflecting on how we might work to counter xenophobia and its fantasies.
The phenotypic spectrum of X‐linked, infantile onset ALG13‐related developmental and epileptic encephalopathy
Authors: Datta Alexandre N. , Bahi‐Buisson Nadia , Bienvenu Thierry , Buerki Sarah E. , Gardiner Fiona , Cross J. Helen , Heron Bénédicte , Kaminska Anna , Korff Christian M. , Lepine Anne , Lesca Gaetan , McTague Amy , Mefford Heather C. , Mignot Cyrill , Milh Matthieu , Piton Amélie , Pressler Ronit M. , Ruf Susanne , Sadleir Lynette G. , de Saint Martin Anne , Van Gassen Koen , Verbeek Nienke E. , Ville Dorothée , Villeneuve Nathalie , Zacher Pia , Scheffer Ingrid E. , Lemke Johannes R.
Published: January 2021

Objective

Asparagine‐linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis.

Methods

We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants.

Results

The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one‐half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one‐third of all cases paroxysms of fast activity with electrodecrement. ALG13‐related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one‐third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired.

Significance

X‐linked ALG13‐related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.
Expanding the phenotype of PIGS‐associated early onset epileptic developmental encephalopathy
Authors: Efthymiou Stephanie , Dutra‐Clarke Marina , Maroofian Reza , Kaiyrzhanov Rauan , Scala Marcello , Reza Alvi Javeria , Sultan Tipu , Christoforou Marilena , Tuyet Mai Nguyen Thi , Mankad Kshitij , Vona Barbara , Rad Aboulfazl , Striano Pasquale , Salpietro Vincenzo , Guillen Sacoto Maria J. , Zaki Maha S. , Gleeson Joseph G. , Campeau Philippe M. , Russell Bianca E. , Houlden Henry
Published: January 2021

The phosphatidylinositol glycan anchor biosynthesis class S protein (PIGS) gene has recently been implicated in a novel congenital disorder of glycosylation resulting in autosomal recessive inherited glycosylphosphatidylinositol‐anchored protein (GPI‐AP) deficiency. Previous studies described seven patients with biallelic variants in the PIGS gene, of whom two presented with fetal akinesia and five with global developmental delay and epileptic developmental encephalopathy. We present the molecular and clinical characteristics of six additional individuals from five families with unreported variants in PIGS. All individuals presented with hypotonia, severe global developmental delay, microcephaly, intractable early infantile epilepsy, and structural brain abnormalities. Additional findings include vision impairment, hearing loss, renal malformation, and hypotonic facial appearances with minor dysmorphic features but without a distinctive facial gestalt. Four individuals died due to neurologic complications. GPI anchoring studies performed on one individual revealed a significant decrease in GPI‐APs. We confirm that biallelic variants in PIGS cause vitamin pyridoxine‐responsive epilepsy due to inherited GPI deficiency and expand the genotype and phenotype of PIGS‐related disorder. Further delineation of the molecular spectrum of PIGS‐related disorders would improve management, help develop treatments, and encourage the expansion of diagnostic genetic testing to include this gene as a potential cause of neurodevelopmental disorders and epilepsy.
A South‐to‐South Cultural Adaptation of an Evidence‐Based Parenting Program for Families in the Philippines
Authors: Mamauag Bernice Landoy , Alampay Liane Peña , Lachman Jamie M. , Madrid Bernadette J. , Hutchings Judy , Ward Catherine L. , Gardner Frances
Published: January 2021

Rates of child maltreatment are higher in low‐ and middle‐income countries due to risk factors such as social inequities, economic adversity, and sociocultural norms. Given the evidence showing the effectiveness of parenting interventions to prevent child maltreatment, this study embarked on a cultural adaptation of an evidence‐based parenting program with the eventual goal of integrating it within a nationwide conditional cash transfer program for low‐income Filipino parents with children aged 2–6 years. We document the systematic adaptation of the Parenting for Lifelong Health for Young Children program that was developed and tested in South Africa, for low‐resource Filipino families using the heuristic framework for the cultural adaptation of interventions. We underscore the merits of conducting a multistage top‐down and bottom‐up process that uses a participatory approach among cultural insiders and outsiders to develop a parenting intervention that reflects the contextual realities and cultural values of end users. The adapted program, Masayang Pamilya Para sa Batang Pilipino, is the product of a delicate and deliberate effort to balance Filipino childrearing goals and values with the scientific evidence on components of parenting interventions known to promote positive parenting and prevent child maltreatment.
Cellular self‐cannibalism helps immune cells fight the flu
Authors: Postoak Joshua Luke , Yang Guan , Wu Lan , Van Kaer Luc
Published: January 2021

CD4 T cells are critical for generating protective immune responses to infection with influenza virus. Although most CD4 T cells react with peptides from extracellular sources, many react with peptides from viral particles synthesized inside cells; however, the pathways employed for processing the latter antigens remain uncertain. Deng et al. provide evidence for a role of autophagy, a cellular self‐eating process, in this unconventional antigen processing route, with potential implications for the development of influenza virus vaccines.
Endodontic implications of a patient with arteriovenous malformation: a case report and literature review
Authors: Chawla A. , Gill S. , Sharma S. , Kumar V. , Logani A.
Published: January 2021

Aim

To present the endodontic management of a patient diagnosed with a high‐flow arteriovenous malformation (AVM) requiring root canal treatment and to discuss the relevant endodontic literature for this rare but significant problem.

AVM is a complex communication of an artery and a vein in which the oxygenated blood is forced away from the intended tissue. The incidence of its occurrence in the face and neck is rare, and when present, the most common sign is gingival bleeding. Arteriovenous malformation is both a diagnostic and therapeutic challenge for dentists. Also, there is ambiguity regarding the precautions to be taken whilst doing endodontic procedures in such cases. Hence, there is a need to understand the disease process and its implications in order to prevent life‐threatening complications during treatment. This case report highlights the successful endodontic management of a cariously exposed right maxillary second premolar in a patient diagnosed with high‐flow AVM. On an orthopantomogram, the AVM was spreading in the left submandibular space involving the left ramus area. The clinical findings of limited mouth opening with inter‐appointment swelling and trismus during treatment made the case unusual and challenging. This paper addresses the current understanding of the classification, diagnosis, clinical features and endodontic management, together with specific guidelines and recommendations whilst performing endodontic procedures in AVM cases.

Key learning points

The classification and oral manifestations of AVM must be known and understood.

Practitioners should be aware of the radiographic appearance of AVM.

Recommended precautions should be taken when carrying out restorative and endodontic procedures in a patient with AVM.

Antibiotic prophylaxis may be considered before endodontic treatment in a patient with AVM.

Multidisciplinary treatment planning may be required.
Deciphering the multifaceted roles of TET proteins in T‐cell lineage specification and malignant transformation
Authors: Tsagaratou Ageliki
Published: January 2021

TET proteins are DNA demethylases that can oxidize 5‐methylcytosine (5mC) to generate 5‐hydroxymethylcytosine (5hmC) and other oxidized mC bases (oxi‐mCs). Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell‐specific gene expression program. In this review, we focus on the role of TET proteins in T‐cell lineage specification. We explore the multifaceted roles of TET proteins in regulating gene expression in the contexts of T‐cell development, lineage specification, function, and disease. Finally, we discuss the future directions and experimental strategies required to decipher the precise mechanisms employed by TET proteins to fine‐tune gene expression and safeguard cell identity.
Regulatory B cells in respiratory health and diseases
Authors: Menon Madhvi , Hussell Tracy , Ali Shuwa Halima
Published: January 2021

B cells are critical mediators of humoral immune responses in the airways through antibody production, antigen presentation, and cytokine secretion. In addition, a subset of B cells, known as regulatory B cells (Bregs), exhibit immunosuppressive functions via diverse regulatory mechanisms. Bregs modulate immune responses via the secretion of IL‐10, IL‐35, and tumor growth factor‐β (TGF‐β), and by direct cell contact. The balance between effector and regulatory B cell functions is critical in the maintenance of immune homeostasis. The importance of Bregs in airway immune responses is emphasized by the different respiratory disorders associated with abnormalities in Breg numbers and function. In this review, we summarize the role of immunosuppressive Bregs in airway inflammatory diseases and highlight the importance of this subset in the maintenance of respiratory health. We propose that improved understanding of signals in the lung microenvironment that drive Breg differentiation can provide novel therapeutic avenues for improved management of respiratory diseases.
Group Cognitive Behavioural Treatment for Anxiety in Autistic Adolescents with Intellectual Disability: A Pilot and Feasibility Study
Authors: Blakeley‐Smith Audrey , Meyer Allison T. , Boles Richard E. , Reaven Judy
Published: January 2021

Background

Adolescents with Autism Spectrum Disorder (ASD) and intellectual disability evidence significant anxiety. This study aimed to adapt a group cognitive behaviour therapies (CBT) programme designed for youth with ASD and anxiety to meet the cognitive, communication, and behavioural needs of adolescents with intellectual disability, and assess initial feasibility and efficacy of the intervention.

Methods

Structural, content and procedural adaptations were made to a 14‐week family‐focused CBT intervention. Twenty‐three adolescents with ASD, intellectual disability and anxiety were included. Treatment acceptability along with adolescent anxiety symptoms was assessed via parent report measures.

Results

Of the 23 participants, 19 completed treatment and attended 94% of sessions. Parent acceptability was high. Significant reductions were noted on anxiety symptoms post‐intervention.

Conclusions

Results indicate that the CBT group was feasible and acceptable. Preliminary outcomes suggest that adolescent anxiety improved, although replication with a larger sample and comparison to a control group is needed.
Repeat catheter ablation for recurrent atrial fibrillation: Electrophysiologic findings and clinical outcomes
Authors: Daimee Usama A. , Akhtar Tauseef , Boyle Thomas A. , Jager Leah , Arbab‐Zadeh Armin , Marine Joseph E. , Berger Ronald D. , Calkins Hugh , Spragg David D.
Published: January 2021

Introduction

Atrial fibrillation (AF) ablation is successful in 60%–80% of optimal candidates, with many patients requiring repeat procedures. We performed a detailed examination of electrophysiologic findings and clinical outcomes associated with first repeat AF ablations in the era of contact force‐sensing radiofrequency (RF) catheters.

Methods

We retrospectively studied patients who underwent their first repeat AF ablations for symptomatic, recurrent AF at our center between 2013 and 2019. All repeat ablations were performed using contact force‐sensing RF catheters. Pulmonary vein (PV) reconnections at repeat ablation and freedom from atrial arrhythmia 1 year after repeat ablation were evaluated. We further assessed these findings based on AF classification at the time of presentation for repeat ablation, index RF versus cryoballoon (CB) ablation, and duration (≥3 versus <3 years) between index and repeat procedures.

Results

Among 300 patients, there were 136 (45.3%) who presented for their first repeat ablations in persistent AF. During repeat ablation, at least one PV reconnection was found in 257 (85.6%) patients, while 159 (53%) had three to four reconnections. There was a similar distribution of reconnections among patients with persistent versus paroxysmal AF (mean: 2.7 ± 1.3 vs. 2.9 ± 1.2; p = .341), index RF versus CB ablation (mean: 2.8 ± 1.3 vs. 2.9 ± 1.2; p = .553), and ≥3 versus <3 years between index and repeat procedures (mean: 3.0 ± 1.1 vs. 2.7 ± 1.3; p = .119). At repeat ablation, the PVs were re‐isolated in all patients, and additional non‐PV ablation was performed in 171 (57%) patients. Freedom from atrial arrhythmia at 1‐year follow‐up after repeat ablation was 66%, similar among those with persistent versus paroxysmal AF (65.4% vs. 66.5%; p = .720), index RF versus CB ablation (66.7% vs. 68.9%; p = .930), and ≥3 versus <3 years between index and repeat ablations (64.4% vs. 66.7%; p = .760). Major complications occurred in a total of 4 (1.3%) patients.

Conclusion

In a contemporary cohort of patients receiving their first repeat AF ablations using contact force‐sensing RF catheters, PV reconnections were common, and freedom from atrial arrhythmia was 66% at 1‐year follow‐up. The distributions of PV reconnections and rates of freedom from atrial arrhythmia were similar, based on persistent versus paroxysmal AF at presentation for repeat ablation, index RF versus CB ablation, and duration between index and repeat procedures. The incidence of major complications was very low.
Permanent His bundle pacing using a new tridimensional delivery sheath and a standard active fixation pacing lead: The telescopic technique
Authors: Zingarini Gianluca , Notaristefano Francesco , Spighi Lorenzo , Bagliani Giuseppe , Cavallini Claudio
Published: January 2021

Introduction

Permanent His bundle pacing (PHBP) preserves physiological ventricular activation but technical difficulties have limited its widespread use. We report the first experience of PHBP performed with a new specific delivery sheath (Selectra 3D, Biotronik, Berlin, Germany) and an extendable‐retractable active screw, stylet‐driven pacing lead (Solia S 60, Biotronik).

Methods and Results

Clinical, procedural, ECG, and electrical data from consecutive patients undergoing PHBP with this system were collected at implantation, and follow‐up was performed after 1 month. Our cohort included 17 patients (71% males; mean age 76 ± 8 years) undergoing permanent pacing for sick sinus syndrome (59%) or atrioventricular block (41%). PHBP was successful in 15 (88%) procedures with mean procedure and fluoroscopy times of 63 ± 14 and 13 ± 5 min, respectively. The pacing threshold was 2.1 ± 1.1 V @1 ms and the sensed R‐wave amplitude was 5.6 ± 3.5 mV; bipolar and unipolar pacing impedances were 526 ± 115 and 369 ± 109 Ω, respectively. At discharge, neither procedure‐related complications nor lead dislodgement or pacing capture failures was reported. After 1 month, 14 (93%) patients still demonstrated His bundle stimulation and one (7%) lost His bundle capture but the lead revision was not necessary because the myocardial pacing threshold was stable. Follow‐up threshold (2 ± 1.1 vs. 2.3 ± 1.2 V@1 ms, p = .239) and sensed R‐wave amplitude (5.6 ± 3.4 vs. 6.4 ± 2.5, p = .403) was unchanged compared to the acute phase.

Conclusion

PHBP performed with a standard active fixation pacing lead and a new delivery sheath for His pacing is feasible, safe and demonstrates clinically acceptable electric performance both at implantation and after 1 month.
The effect of pursed‐lip breathing combined with number counting on blood pressure and heart rate in hypertensive urgency patients: A randomized controlled trial
Authors: Mitsungnern Thapanawong , Srimookda Nipa , Imoun Supap , Wansupong Suntaraporn , Kotruchin Praew
Published: January 2021

Hypertensive urgency (HT urgency) is an alarming sign of uncontrolled hypertension. It is aggravated by nonadherence to medication, as well as psychosocial stress. Mindfulness is beneficial for reducing stress, while deep and slow breathing is effective for lowering blood pressure (BP). In our study, we aimed to assess BP and heart rate effects in HT urgency patients practicing pursed‐lip breathing and number counting (PLB with NC)—a practice that promotes mindfulness with deep/slow breathing patterns. In a randomized controlled trial, 110 patients were equally allocated to intervention and control groups. The intervention group was trained and encouraged to do PLB with NC during their emergency room admission, while the control group received conventional medical care. The mean systolic BP (SBP), diastolic BP (DBP), and HR of the intervention group in the 3rd hour were significantly lower than the baseline values at −28.2 mm Hg (95%CI;‐23.5 to −32.4), −17.1 mm Hg (95%CI;‐14.2 to −20.0), and −4.9 beats per minute (bpm) (95%CI;‐4.0 to −5.8), respectively. In the control group, both the mean SBP and DBP were also significantly lower in the 3rd hour. However, HR reduction was inconclusive. When the two groups were compared, a greater degree of reduction was found in the intervention group for SBP (9.80 mm Hg, 95%CI; 4.10 to 15.50), DBP (7.69 mm Hg, 95%CI; 3.61 to 11.77), and HR (3.85 bpm, 95%CI; 1.99 to 5.72). In conclusion, PLB with NC was effective for lowering BP and HR. It might be used as a complementary treatment for HT urgency patients.
Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation
Authors: Jiang Yuchuan , Chen Peng , Hu Kaishun , Dai Guanqi , Li Jinying , Zheng Dandan , Yuan Hui , He Lu , Xie Penghui , Tu Mengxian , Peng Shuang , Qu Chen , Lin Wenyu , Chung Raymond T. , Hong Jian
Published: January 2021

The pro‐inflammatory and pro‐fibrotic liver microenvironment facilitates hepatocarcinogenesis. However, the effects and mechanisms by which the hepatic fibroinflammatory microenvironment modulates intrahepatic hepatocellular carcinoma (HCC) progression and its response to systematic therapy remain largely unexplored. We established a syngeneic orthotopic HCC mouse model with a series of persistent liver injury induced by CCl4 gavage, which mimic the dynamic effect of hepatic pathology microenvironment on intrahepatic HCC growth and metastasis. Non‐invasive bioluminescence imaging was applied to follow tumour progression over time. The effect of the liver microenvironment modulated by hepatic injury on sorafenib resistance was investigated in vivo and in vitro. We found that the persistent liver injury facilitated HCC growth and metastasis, which was positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. The inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), both promoted intrahepatic HCC progression via STAT3 activation. In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti‐apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I‐201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up‐regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3.
Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial‐mesenchymal transition of a endometrial epithelial cells
Authors: Yu Qin , Wang Jianzhang , Li Tiantian , Guo Xinyue , Ding Shaojie , Che Xuan , Zhu Libo , Peng Yangying , Xu Xinxin , Zou Gen , Zhang Xinmei
Published: January 2021

Endometriosis is a benign, chronic inflammatory disease that commonly occurs in reproductive‐aged women. Epithelial‐mesenchymal transition (EMT) of endometrial epithelial cells plays an important role in the development of endometriosis. Recepteur d'origine nantais (RON), a receptor tyrosine kinase, has been reported to promote EMT and progression in tumours. However, whether and how RON mediates the EMT and endometriosis development is not known. Here, we found that RON activation could improve the migratory and invasive capabilities, change cellular morphologies, and decrease expression of E‐cadherin and increase expression of N‐cadherin in endometrial epithelial cells. Inhibition or knockdown of RON expression suppressed the migration and invasion of endometrial epithelial cells. Our studies also indicated that RON played its part in endometrial epithelial cells through protein kinase B (Akt) and mitogen‐activated protein kinase (MAPK) pathways. Treatment with a RON inhibitor could decrease the number of ectopic lesions in a mouse model of endometriosis and mediate expression of EMT markers in endometriotic lesions. These data suggest that RON contributed to endometriosis development by promoting EMT of endometrial epithelial cells. Therefore, RON may be a new therapeutic target for endometriosis.
Pan‐Africanism, Participation and Legitimation in the African Governance Architecture
Authors: Mickler David , Sturman Kathryn
Published: January 2021

This article examines how contending appeals to pan‐Africanism have been central to the (de)legitimation processes that have shaped the trajectory of African regional governance. Such appeals have been used variously to construct and contest the scale, pace and norms constituting continental integration, including its modes of participation. The African Union (AU) remains a site of contestation over the internal legitimation of competing pan‐African agendas as well as external legitimation in the face of interested global forces. We draw on relevant scholarly works, policy documents and interviews with AU practitioners to examine the AU's African Governance Architecture as a set of continental agencies, principles and processes claiming to promote a democratic governance agenda premised on pan‐African Shared Values and wider participation. We demonstrate how the particular functioning of several nascent participatory innovations under AGA reflects ongoing contestation over the form and function of African regional governance.
Sex differences in the association between fatty liver and type 2 diabetes incidence in non‐obese Japanese: A retrospective cohort study
Authors: Narisada Akihiko , Shibata Eiji , Hasegawa Tomomi , Masamura Nobue , Taneda Chitose , Suzuki Kohta
Published: January 2021

Aims/Introduction

Asians develop type 2 diabetes at a lower body mass index (BMI) compared with other races, which is partly because of Asian‐specific fat depots. Sex plays a role in fat deposition, regardless of race. This retrospective cohort study aimed to investigate the association among fatty liver, sex and type 2 diabetes in non‐obese Japanese.

Materials and Methods

The participants in this study (13,596 men and 6,037 women) were aged 30–64 years, and had undergone health checkups between 2013 and 2015, in Aichi, Japan. Baseline BMI was categorized as follows: <18.5, 18.5–19.9, 20–22.9, 23–24.9, 25–27.4 and ≥27.5 kg/m2. Fatty liver was diagnosed by abdominal ultrasonography. The joint effect of BMI and fatty liver on the incidence of type 2 diabetes was assessed, stratified by sex.

Results

During follow up, 738 men and 138 women developed type 2 diabetes. Compared with the BMI of 20–22.9 kg/m2 without fatty liver group, the BMI of 20–22.9 kg/m2 with fatty liver was associated with a higher risk of type 2 diabetes in men, but not in women. Furthermore, men with a BMI of 23–24.9 and 25–27.4 kg/m2 without fatty liver had no significant type 2 diabetes risk, whereas women with a BMI of 23–24.9 and 25–27.4 kg/m2, regardless of fatty liver, had an increased risk.

Conclusions

These results suggest the association between fatty liver and type 2 diabetes in non‐obese Asians is different by sex; fatty liver increases diabetes risk among male, not female, non‐obese Asians.
Immediate implant placement and loading in the esthetic area when the buccal socket wall is significantly damaged
Authors: Tirone Federico , Genovesi Francesco
Published: January 2021

Objectives

Recent clinical recommendations contraindicate immediate implant placement when the socket buccal bone plate is significantly damaged. The connective tissue graft (CTG) is increasingly being used in implant therapy and can replace periodontal defects lacking bone wall in periodontal regenerative surgery. Therefore, CTG could be used to allow immediate implant placement and loading even when the buccal socket wall is damaged, facilitating graft material stability.

Clinical considerations

In the first case, deep bone dehiscence was caused by a vertical root fracture. In the second case, a big bone fenestration was caused by a chronic endodontic periapical lesion. Both cases were treated with immediate implant placement and loading. A buccal CTG was used to compensate for the lack of bone and allow stabilization of the particulate xenograft in the gap between the implant and the damaged buccal socket wall. In both cases, a provisional screw‐retained crown was immediately delivered, and the definitive layered zirconia crown was delivered after 3 months. Esthetic results and patient satisfaction monitored for 1 year after loading proved to be encouraging.

Conclusions

Although further investigations with longer follow‐up are required, the approach is likely to yield good results after 1 year of loading.

Clinical Significance

The purpose of this report is to show a surgical approach that seems to be able to overcome the contraindication of the quoted consensus report, which allows for good esthetic results and patient satisfaction even when the buccal bone wall of the extraction socket has been more than 50% compromised, allowing treatment time and cost reduction.
Molecular hydrogen enhances osteogenesis in Danio rerio embryos
Authors: Carnovali Marta , Mariotti Massimo , Banfi Giuseppe
Published: January 2021

Molecular hydrogen (H2) has been reported to have important biological effects on bone tissue in several in vitro and in vivo models. Danio rerio (zebrafish) embryo is a good model to study osteogenesis because of its transparency, size and rapid development. In zebrafish embryo, hydrogen‐rich water (HRW) does not affect vitality or growth rate up to 15%. In addition, 7% HRW treatment enhances zebrafish embryo osteogenesis, increasing the vertebral mineralization rate. In conclusion, we demonstrated the beneficial effects of hydrogen on anabolic bone functions in vivo.
Statin Use in Older Adults with Stable Atherosclerotic Cardiovascular Disease
Authors: Spencer‐Bonilla Gabriela , Chung Sukyung , Sarraju Ashish , Heidenreich Paul , Palaniappan Latha , Rodriguez Fatima
Published: January 2021

Background/Objectives

Older adults (>75 years of age) represent two‐thirds of atherosclerotic cardiovascular disease (ASCVD) deaths. The 2013 and 2018 American multi‐society cholesterol guidelines recommend using at least moderate intensity statins for older adults with ASCVD. We examined annual trends and statin prescribing patterns in a multiethnic population of older adults with ASCVD.

Design

Retrospective longitudinal study using electronic health record (EHR) data from 2007 to 2018.

Setting

A large multi‐specialty health system in Northern California.

Participants

A total of 24,651 adults older than 75 years with ASCVD.

Measurements

Statin prescriptions for older adults with known ASCVD were trended over time. Multivariable regression models were used to identify predictors of statin prescription (logistic) after controlling for relevant demographic and clinical factors.

Results

The study cohort included 24,651 patients older than 75 years; 48% were women. Although prescriptions for moderate/high intensity statins increased over time for adults over 75, fewer than half of the patients (45%) received moderate/high intensity statins in 2018. Women (odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.74, 0.80), patients who had heart failure (OR = 0.69; 95% CI = 0.65, 0.74), those with dementia (OR = 0.88; 95% CI = 0.82, 0.95) and patients who were underweight (OR = 0.64; 95% CI = 0.57, 0.73) were less likely to receive moderate/high intensity statins.

Conclusions

Despite increasing prescription rates between 2007 and 2018, guideline‐recommended statins remained underused in older adults with ASCVD, with more pronounced disparities among women and those with certain comorbidities. Future studies are warranted to examine reasons for statin underuse in older adults with ASCVD.
Morphologic assessment of hypertonic citrate adenine, histidine–tryptophan–ketoglutarate, and university of Wisconsin solutions for hypothermic uterus preservation in rats
Authors: Liu Yu , Ding Yan , Zhang Xuyin , Zhang Ying , Hua Keqin
Published: January 2021

Aim

Optimizing perfusate for static cold storage is one of the key ways of reducing organ dysfunction and rejection in organ transplantation. Here, we tested the effectiveness of the three different solutions for hypothermic uterus preservation.

Methods

Twenty rats were divided into four groups, five in each group. Uterine grafts were retrieved and perfused in situ. The uteri were preserved at 4°C in normal saline as control group (group NS), hypertonic citrate adenine (group HCA), histidine–tryptophan–ketoglutarate (group HTK), or university of Wisconsin solutions (group UW) for 0, 12, 24, and 48 h, respectively. HE, electron microscopy, TUNEL staining, and Cleaved Caspase3 immunohistochemical staining were assessed at each time point.

Results

There was no significant difference in the uterine retrieval time, perfusion time, and the amount of perfusion solution in NS, HCA, HTK, and UW groups (p > 0.05). HCA and HTK can well preserve the pathological morphology of rat uterine tissues for up to 24 h, and the apoptosis rates of the two groups are 7.2% and 7.1%, respectively, with no statistical difference (p > 0.05). Still, the protective effect of HTK on the ultrastructure of cells was much better than HCA. There was a significant difference in the apoptosis rate of UW (6.5%), HTK (8.8%), and HCA (9.4%) at 48 h, with mitochondrial and endoplasmic reticulum structure well preserved only in UW.

Conclusion

At 4°C, normal saline is not suitable to preserve rat uterus for more than 12 h. The morphologic results would favor the use of HTK rather than HCA for short‐term hypothermic uterus preservation (≤24 h). UW is better than HTK and HCA for 48 h hypothermic uterus preservation.