bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up
Authors: Serra Gregorio , Antona Vincenzo , Giuffré Mario , Li Pomi Federica , Lo Scalzo Lucia , Piro Ettore , Schierz Ingrid Anne Mandy , Corsello Giovanni 
Published: September 2021

Abstract
Introduction
Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing.

Patient’s presentation
We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities.

Conclusions
Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.
Activity of the mouse Notch ligand DLL1 is sensitive to C-terminal tagging in vivo
Authors: Schuster-Gossler Karin , Boldt Karsten , Bornhorst Dorothee , Delany-Heiken Patricia , Ueffing Marius , Gossler Achim 
Published: September 2021

Abstract
Objective
The mammalian Notch ligand DLL1 has essential functions during development. To visualise DLL1 in tissues, for sorting and enrichment of DLL1-expressing cells, and to efficiently purify DLL1 protein complexes we tagged DLL1 in mice with AcGFPHA or Strep/FLAG.

Results
We generated constructs to express DLL1 that carried C-terminal in-frame an AcGFPHA tag flanked by loxP sites followed by a Strep/FLAG (SF) tag out of frame. Cre-mediated recombination replaced AcGFP-HA by SF. The AcGFPHAstopSF cassette was added to DLL1 for tests in cultured cells and introduced into endogenous DLL1 in mice by homologous recombination. Tagged DLL1 protein was detected by antibodies against GFP and HA or Flag, respectively, both in CHO cells and embryo lysates. In CHO cells the AcGFP fluorophore fused to DLL1 was functional. In vivo AcGFP expression was below the level of detection by direct fluorescence. However, the SF tag allowed us to specifically purify DLL1 complexes from embryo lysates. Homozygous mice expressing AcGFPHA or SF-tagged DLL1 revealed a vertebral column phenotype reminiscent of disturbances in AP polarity during somitogenesis, a process most sensitive to reduced DLL1 function. Thus, even small C-terminal tags can impinge on sensitive developmental processes requiring DLL1 activity.
Fabrication of alginate-based hydrogel cross-linked via horseradish peroxidase for articular cartilage engineering
Authors: Saghati Sepideh , Khoshfetrat Ali Baradar , Tayefi Nasrabadi Hamid , Roshangar Leila , Rahbarghazi Reza 
Published: September 2021

Abstract
Objective
We aimed to detect the effect of a couple of parameters including Alg, H2O2, and HRP concentrations on the gelation time of Alg-based hydrogels using an enzymatic cross-linked procedure.

Results
NMR, UV–Vis, and ATR-FTIR analyses confirmed the conjugation of Ph to the Alg backbone. Data showed gelation time was delayed with the increase and reduction of H2O2 and HRP, respectively. We noted that hydrogel consisted of 1.2% (w/v) Alg, 5 U HRP, and 100 mM H2O2 yielded an appropriate gelation time with appropriate mechanical properties. The addition of 0.5% (v/v) Col developed hydrogel increased the gelation time. The data showed that Alg, HRP, and H2O2 with the ratio of 1:0.54:0.54 had proper physicochemical features for cartilage engineering.
Investigating the DNA methylation profile of e-cigarette use
Authors: Richmond Rebecca C. , Sillero-Rejon Carlos , Khouja Jasmine N. , Prince Claire , Board Alexander , Sharp Gemma , Suderman Matthew , Relton Caroline L. , Munafò Marcus , Gage Suzanne H. 
Published: September 2021

AbstractBackgroundLittle evidence exists on the health effects of e-cigarette use. DNA methylation may serve as a biomarker for exposure and could be predictive of future health risk. We aimed to investigate the DNA methylation profile of e-cigarette use.ResultsAmong 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. DNA methylation at 7 cytosine-phosphate-guanine sites (CpGs) was associated with e-cigarette use atp < 1 × 10–5and none atp < 5.91 × 10–8. 13 CpGs were associated with smoking atp < 1 × 10–5and one atp < 5.91 × 10–8. CpGs associated with e-cigarette use were largely distinct from those associated with smoking. There was strong enrichment of known smoking-related CpGs in the smokers but not the vapers. We also tested associations between e-cigarette use and methylation scores known to predict smoking and biological ageing. Methylation scores for smoking and biological ageing were similar between vapers and non-smokers. Higher levels of all smoking scores and a biological ageing score (GrimAge) were observed in smokers. A methylation score for e-cigarette use showed poor prediction internally (AUC 0.55, 0.41–0.69) and externally (AUC 0.57, 0.36–0.74) compared with a smoking score (AUCs 0.80) and was less able to discriminate lung squamous cell carcinoma from adjacent normal tissue (AUC 0.64, 0.52–0.76 versus AUC 0.73, 0.61–0.85).ConclusionsThe DNA methylation profile for e-cigarette use is largely distinct from that of cigarette smoking, did not replicate in independent samples, and was unable to discriminate lung cancer from normal tissue. The extent to which methylation related to long-term e-cigarette use translates into chronic effects requires further investigation.
Machine learning methods for predicting progression from mild cognitive impairment to Alzheimer’s disease dementia: a systematic review
Authors: Grueso Sergio , Viejo-Sobera Raquel 
Published: September 2021

Abstract
Background
An increase in lifespan in our society is a double-edged sword that entails a growing number of patients with neurocognitive disorders, Alzheimer’s disease being the most prevalent. Advances in medical imaging and computational power enable new methods for the early detection of neurocognitive disorders with the goal of preventing or reducing cognitive decline. Computer-aided image analysis and early detection of changes in cognition is a promising approach for patients with mild cognitive impairment, sometimes a prodromal stage of Alzheimer’s disease dementia.

Methods
We conducted a systematic review following PRISMA guidelines of studies where machine learning was applied to neuroimaging data in order to predict whether patients with mild cognitive impairment might develop Alzheimer’s disease dementia or remain stable. After removing duplicates, we screened 452 studies and selected 116 for qualitative analysis.

Results
Most studies used magnetic resonance image (MRI) and positron emission tomography (PET) data but also magnetoencephalography. The datasets were mainly extracted from the Alzheimer’s disease neuroimaging initiative (ADNI) database with some exceptions. Regarding the algorithms used, the most common was support vector machine with a mean accuracy of 75.4%, but convolutional neural networks achieved a higher mean accuracy of 78.5%. Studies combining MRI and PET achieved overall better classification accuracy than studies that only used one neuroimaging technique. In general, the more complex models such as those based on deep learning, combined with multimodal and multidimensional data (neuroimaging, clinical, cognitive, genetic, and behavioral) achieved the best performance.

Conclusions
Although the performance of the different methods still has room for improvement, the results are promising and this methodology has a great potential as a support tool for clinicians and healthcare professionals.
Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis
Authors: Ning Hongjuan , Chen Haixu , Deng Jingyu , Xiao Chun , Xu Moyan , Shan Lina , Yang Chao , Zhang Zheng 
Published: September 2021

Abstract
Background
Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair.

Methods
Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization.

Results
Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis.

Conclusions
FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.
Association between delay in intensive care unit admission and the host response in patients with community-acquired pneumonia
Authors: Pereverzeva Liza , Uhel Fabrice , Peters Sengers Hessel , Cremer Olaf L. , Schultz Marcus J. , Bonten Marc M. J. , Scicluna Brendon P. , van der Poll Tom ,   the MARS consortium
Published: September 2021

Abstract
Background
A delay in admission to the intensive care unit (ICU) of patients with community-acquired pneumonia (CAP) has been associated with an increased mortality. Decisions regarding interventions and eligibility for immune modulatory therapy are often made at the time of admission to the ICU. The primary aim of this study was to compare the host immune response measured upon ICU admission in CAP patients admitted immediately from the emergency department (direct ICU admission) with those who were transferred within 72 h after admission to the general ward (delayed ICU admission).

Methods
Sixteen host response biomarkers providing insight in pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.

Results
Of 530 ICU admissions with CAP, 387 (73.0%) were directly admitted and 143 (27.0%) had a delayed admission. Patients with a delayed ICU admission were more often immunocompromised (35.0 versus 21.2%, P = .002) and had more malignancies (23.1 versus 13.4%, P = .011). Shock was more present in patients who were admitted to the ICU directly (46.6 versus 33.6%, P = .010). Delayed ICU admission was not associated with an increased hospital mortality risk (hazard ratio 1.25, 95% CI 0.89–1.78, P = .20). The plasma levels of biomarkers (n = 297) reflecting systemic inflammation, endothelial cell activation and coagulation activation were largely similar between groups, with exception of C-reactive protein, soluble intercellular adhesion molecule-1 and angiopoietin-1, which were more aberrant in delayed admissions compared to direct ICU admissions. Blood leukocyte transcriptomes (n = 132) of patients with a delayed ICU admission showed blunted innate and adaptive immune response signalling when compared with direct ICU admissions, as well as decreased gene expression associated with tissue repair and extracellular matrix remodelling pathways.

Conclusions
Blood leukocytes of CAP patients with delayed ICU admission show evidence of a more immune suppressive phenotype upon ICU admission when compared with blood leukocytes from patients directly transferred to the ICU.
Trial registration: Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project, ClinicalTrials.gov identifier NCT01905033.
Local existence–uniqueness and monotone iterative approximation of positive solutions for p-Laplacian differential equations involving tempered fractional derivatives
Authors: Zhou Bibo , Zhang Lingling 
Published: September 2021

AbstractIn this paper, we are concerned with a kind of tempered fractional differential equation Riemann–Stieltjes integral boundary value problems with p-Laplacian operators. By means of the sum-type mixed monotone operators fixed point theorem based on the cone $P_{h}$

P
h

, we obtain not only the local existence with a unique positive solution, but also construct two successively monotone iterative sequences for approximating the unique positive solution. Finally, we present an example to illustrate our main results.
Determinants of influenza vaccine hesitancy among pregnant women in Europe: a systematic review
Authors: Adeyanju Gbadebo Collins , Engel Elena , Koch Laura , Ranzinger Tabea , Shahid Imtiaz Bin Mohammed , Head Micheal G. , Eitze Sarah , Betsch Cornelia 
Published: September 2021

Abstract
Background
Pregnant women are at high risk for severe influenza. However, maternal influenza vaccination uptake in most World Health Organization (WHO) European Region countries remains low, despite the presence of widespread national recommendations. An influenza vaccination reduces influenza-associated morbidity and mortality in pregnancy, as well as providing newborns with protection in their first months. Potential determinants of vaccine hesitancy need to be identified to develop strategies that can increase vaccine acceptance and uptake among pregnant women. The primary objective of the systematic review is to identify the individual determinants of influenza vaccine hesitancy among pregnant women in Europe, and how to overcome the hesitancy.

Methods
Databases were searched for peer-reviewed qualitative and quantitative studies published between 2009 and 2019 inclusive. Databases included PubMed via MEDLINE, Cochrane Central Register for Controlled Trials, PsycINFO, SAGE Journals, Taylor and Francis and Springer nature. These covered themes including psychology, medicine, and public health. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, 11 studies were eligible and analyzed for significant determinants of influenza vaccine hesitancy among pregnant women in Europe.

Results
The most commonly reported factors were psychological aspects, for example concerns about safety and risks to mother and child, or general low risk perception of becoming ill from influenza. Doubts about the effectiveness of the vaccine and a lack of knowledge about this topic were further factors. There was also influence of contextual factors, such as healthcare workers not providing adequate knowledge about the influenza vaccine or the pregnant lady stating their antivaccine sentiment.

Conclusion
Health promotion that specifically increases knowledge among pregnant women about influenza and vaccination is important, supporting a valid risk judgment by the pregnant lady. The development of new information strategies for dialogue between healthcare providers and pregnant women should form part of this strategy.
Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta
Authors: Rofo Fadi , Buijs Jos , Falk Ronny , Honek Ken , Lannfelt Lars , Lilja Anna M. , Metzendorf Nicole G. , Gustavsson Tobias , Sehlin Dag , Söderberg Linda , Hultqvist Greta 
Published: September 2021

AbstractBackgroundAmyloid-β (Aβ) immunotherapy is a promising therapeutic strategy in the fight against Alzheimer’s disease (AD). A number of monoclonal antibodies have entered clinical trials for AD. Some of them have failed due to the lack of efficacy or side-effects, two antibodies are currently in phase 3, and one has been approved by FDA. The soluble intermediate aggregated species of Aβ, termed oligomers and protofibrils, are believed to be key pathogenic forms, responsible for synaptic and neuronal degeneration in AD. Therefore, antibodies that can strongly and selectively bind to these soluble intermediate aggregates are of great diagnostic and therapeutic interest.MethodsWe designed and recombinantly produced a hexavalent antibody based on mAb158, an Aβ protofibril-selective antibody. The humanized version of mAb158, lecanemab (BAN2401), is currently in phase 3 clinical trials for the treatment of AD. The new designs involved recombinantly fusing single-chain fragment variables to the N-terminal ends of mAb158 antibody. Real-time interaction analysis with LigandTracer and surface plasmon resonance were used to evaluate the kinetic binding properties of the generated antibodies to Aβ protofibrils. Different ELISA setups were applied to demonstrate the binding strength of the hexavalent antibody to Aβ aggregates of different sizes. Finally, the ability of the antibodies to protect cells from Aβ-induced effects was evaluated by MTT assay.ResultsUsing real-time interaction analysis with LigandTracer, the hexavalent design promoted a 40-times enhanced binding with avidity to protofibrils, and most of the added binding strength was attributed to the reduced rate of dissociation. Furthermore, ELISA experiments demonstrated that the hexavalent design also had strong binding to small oligomers, while retaining weak and intermediate binding to monomers and insoluble fibrils. The hexavalent antibody also reduced cell death induced by a mixture of soluble Aβ aggregates.ConclusionWe provide a new antibody design with increased valency to promote binding avidity to an enhanced range of sizes of Aβ aggregates. This approach should be general and work for any aggregated protein or repetitive target.
Laparoscopic approach for surgical treatment of pleuroperitoneal communication interfering with peritoneal dialysis: a case report
Authors: Yorinaga Satoko , Maki Takehiro , Kawai Noriko , Kaneko Hiroyuki , Misu Kenjiro , Inomata Hitoshi , Omi Makoto , Hirano Satoshi 
Published: September 2021

Abstract
Background
Pleuroperitoneal communication is a rare disorder that interferes with peritoneal dialysis. Although favorable results of thoracoscopic fistula closure have been reported, there are some cases in which the fistulas cannot be identified by thoracoscopy and the patients are forced to switch to hemodialysis.

Case presentation
We present two cases of pleuroperitoneal communication in which diaphragmatic fistulas could not be identified thoracoscopically, but could be identified laparoscopically. Patient 1 had difficulty continuing peritoneal dialysis 9 months after its introduction due to right pleural effusion. Although we could not detect the fistula thoracoscopically, we could laparoscopically identify the fistula in the center of the tendon of the right diaphragm and closed the site from the thoracic side. Patient 2 developed dyspnea due to right pleural effusion 6 months after the introduction of peritoneal dialysis. We could not find the fistulas with a thoracoscopic approach, but could identify multiple diaphragmatic fistulas with a laparoscopic approach and close the sites from the thoracic side.

Conclusion
In the surgical treatment of pleuroperitoneal communication, diaphragmatic fistulas can be identified laparoscopically even when thoracoscopic observation fails to find any fistulas.
Anesthetic implications and role of preoperative beta blockade in esophageal substitution with stomach in pediatric surgical patients
Authors: Kundal Raksha , Singh Ranju , Choudhury Subhasis Roy , Yadav Partap Singh , Kumar Ajai , Gupta Shalu , Kundal Vijay Kumar 
Published: September 2021

Abstract
Background
There is a paucity of literature on the anesthetic management of pediatric esophageal substitution using the stomach. We did a retrospective analysis of all such cases done at our institution. We analyzed the patient’s demography, indication, and type of surgery, co-morbid conditions, anesthesia techniques, duration of postoperative ventilation, hospital stay, complications, and mortality. The use of beta-blockers and their effect on the incidence of intraoperative and postoperative tachycardia in gastric pull-up patients was also analyzed.

Results
Thirty-four cases of gastric substitution of the esophagus in children were done over 19-year period; gastric pull-up was done in 28 patients and a gastric tube was made in 6 patients. General anesthesia was given to all; a thoracic epidural for pain was sited in 25 patients. Twenty-eight patients were ventilated postoperatively; the mean duration of ventilation is 54 h. Significant intraoperative tachycardia was observed in 85.7% of patients without beta-blocker as compared to 23.8% patients with beta-blocker (p = 0.004). Postoperatively, tachycardia was absent in patients receiving beta-blocker and present in 71.4% of patients not receiving beta-blockers (p < 0.001). Overall mortality was 8.8% but mortality due to cardiac arrhythmia was 42.9% in the patients not receiving beta-blockers (p = 0.001).

Conclusions
A thorough preoperative preparation, control of tachyarrhythmias, postoperative ventilation, and pain management is recommended for a favorable outcome. In addition, our paper supports the preoperative use of beta-blockers in reducing the incidence of fatal tachyarrhythmias associated with gastric pull-up surgery without any serious adverse effects.

Level of evidence
Level III