bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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.
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

AbstractAimTo 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.SummaryAVM 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

AbstractTET 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

AbstractB 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

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

AbstractIntroductionAtrial 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.MethodsWe 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.ResultsAmong 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.ConclusionIn 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

AbstractIntroductionPermanent 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 ResultsClinical, 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.ConclusionPHBP 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

AbstractHypertensive 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

AbstractThe 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

AbstractEndometriosis 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

AbstractThis 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

AbstractAims/IntroductionAsians 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 MethodsThe 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.ResultsDuring 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.ConclusionsThese 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

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

AbstractMolecular 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.