bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial 13513G>A Mutation With Low Mutant Load Presenting as Isolated Leber's Hereditary Optic Neuropathy Assessed by Next Generation Sequencing
Authors: Sun Chuan-bin , Bai Hai-xia , Xu Dan-ni , Xiao Qing , Liu Zhe 
Published: March 2021

Objective: Mitochondrial 13513G&gt;A mutation presenting as isolated Leber's hereditary optic neuropathy (LHON) without any extraocular pathology has not been reported in literature. We herein evaluate the clinical characteristics and heteroplasmy of m.13513G&gt;A mutation manifesting as isolated LHON.Methods: Seven members of a Chinese family were enrolled in this study. All subjects underwent detailed systemic and ophthalmic examinations. Mitochondrial DNA in their blood was assessed by targeted PCR amplifications, next generation sequencing (NGS), and pyrosequencing. One hundred of blood samples from ethnic-matched healthy volunteers were tested by NGS and pyrosequencing as normal controls.Results: Isolated LHON without any other ocular or extraocular pathology was identified in a 16 year old patient in this family. Heteroplasmic m.13513G&gt;A mutation was detected by NGS of the full mtDNA genome in the patient with mutant load of 33.56%, and of 26% 3 months and 3 years after the onset of LHON, respectively. No m.13513G&gt;A mutation was detected in all his relatives by NGS. Pyrosequencing revealed the mutant load of m.13513G&gt;A mutation of the LHON patient, his mother, father and sister were 22.4, 1.9, 0, and 0%, respectively. None of 100 healthy control subjects was detected to harbor m.13513G&gt;A mutation either by NGS or by pyrosequencing of the full mt DNA genome.Conclusions: We first report m.13513G&gt;A mutation with low mutant load presenting as isolated LHON. NGS of the full mitochondrial DNA genome is highly recommended for LHON suspects when targeted PCR amplification for main primary point mutations of LHON was negative.
The Association of Meat Intake With All-Cause Mortality and Acute Myocardial Infarction Is Age-Dependent in Patients With Stable Angina Pectoris
Authors: Matre Åslaug O. , Van Parys Anthea , Olsen Thomas , Haugsgjerd Teresa R. , Baravelli Carl M. , Nygård Ottar , Dierkes Jutta , Lysne Vegard 
Published: March 2021

Background: Red and processed meat intake have been associated with increased risk of morbidity and mortality, and a restricted intake is encouraged in patients with cardiovascular disease. However, evidence on the association between total meat intake and clinical outcomes in this patient group is lacking.Objectives: To investigate the association between total meat intake and risk of all-cause mortality, acute myocardial infarction, cancer, and gastrointestinal cancer in patients with stable angina pectoris. We also investigated whether age modified these associations.Materials and Methods: This prospective cohort study consisted of 1,929 patients (80% male, mean age 62 years) with stable angina pectoris from the Western Norway B-Vitamin Intervention Trial. Dietary assessment was performed by the administration of a semi-quantitative food frequency questionnaire. Cox proportional hazards models were used to investigate the association between a relative increase in total meat intake and the outcomes of interest.Results: The association per 50 g/1,000 kcal higher intake of total meat with morbidity and mortality were generally inconclusive but indicated an increased risk of acute myocardial infarction [HR: 1.26 (95% CI: 0.98, 1.61)] and gastrointestinal cancer [1.23 (0.70, 2.16)]. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and acute myocardial infarction among younger individuals, but an attenuation, and even reversal of the risk association with increasing age.Conclusion: Our findings support the current dietary guidelines emphasizing a restricted meat intake in cardiovascular disease patients but highlights the need for further research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population.
Photodynamic Therapy as an Alternative Therapeutic Tool in Functionally Inoperable Oral and Oropharyngeal Carcinoma: A Single Tertiary Center Retrospective Cohort Analysis
Authors: Lambert Arnaud , Nees Lotte , Nuyts Sandra , Clement Paul , Meulemans Jeroen , Delaere Pierre , Vander Poorten Vincent 
Published: March 2021

Background: Head and neck cancer is typically treated with surgery, radiotherapy, chemoradiation, or a combination of these treatments. This study aims to retrospectively analyse oncological outcomes, adverse events and toxicity of treatment with temoporfin-mediated photodynamic therapy at a single tertiary referral center. More specifically, in a selected group of patients with otherwise (functionally) inoperable oral or oropharyngeal head and neck squamous cell carcinoma.Methods: Twenty-six consecutive patients who received photodynamic therapy for oral or oropharyngeal squamous cell carcinoma from January 2002 until July 2019 at the University Hospitals Leuven were included. These were (1) patients with an accessible recurrent or new primary tumor in an extensively treated area of the head and neck, not suitable for standard treatment, or (2) patients that were judged medically unfit to undergo standard treatment modalities.Results: Complete tumor response immediately after PDT was obtained in 76.9% of cases. During follow-up, a proportion of CR patients did recur, to reach recurrence-free rates at six months, one year and two years of 60.6%, 48.5% and 32.3%. Local control at the PDT treated area was 42.3% with a median recurrence free interval time of 9 months. Recurrence-free interval was statistically more favorable for oropharyngeal squamous cell carcinoma (with or without oral cavity extension) in comparison to oral cavity squamous cell carcinoma alone (p &lt; 0.001). During a median follow-up period of 27 months, we report new tumor activity in 80.8% of patients. Median overall and disease-specific survival time was 31 and 34 months, respectively. Most reported adverse events were pain after treatment and facial edema. At the end of follow-up, swallowing and upper airway functionality were preserved in 76.9 and 95.7% of patients, respectively.Conclusion: Photodynamic therapy is a valuable treatment option in highly selected patients with oral and/or oropharyngeal (functionally) inoperable head and neck squamous cell carcinoma. Treatment with this alternative modality can induce durable local control in an important fraction of treated patients, with an acceptable toxicity profile.
Identification of Potential Diagnostic Gene Targets for Pediatric Sepsis Based on Bioinformatics and Machine Learning
Authors: Qiao Ying , Zhang Bo , Liu Ying 
Published: March 2021

Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens.Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case–control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method.Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research.
Lower Leg Fractures in Children and Adolescents—Comparison of Conservative vs. ECMES Treatment
Authors: Weber Birte , Kalbitz Miriam , Baur Meike , Braun Christian Karl , Zwingmann Jörn , Pressmar Jochen 
Published: March 2021

Background: Lower leg fractures are one of the most common fractures in pediatric age. In general, treatment of lower leg fractures is predominantly non-operative, requiring clinical and radiological controls. Nevertheless, it can be observed that in recent years tibial shaft fractures have increasingly been treated surgically. The aim of the present study is to investigate treatment strategies in the context of different fracture types of the lower leg.Methods: In this retrospective chart review, we analyzed 168 children with a diaphyseal fracture of the lower leg admitted to a trauma center between 2005 and 2017. The fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF).Results: The frequency of fractures based on the AO-PCCF classification was as follows: Simple oblique fracture of the tibia (43.5%, n = 73), hereof 32 toddler's fractures, multifragmentary oblique fracture of the tibia in 14.3% (n = 24) and simple oblique fracture of both, tibia and fibula in 18 patients (10.7%). Most pediatric fractures were treated conservatively by cast (n = 125). Thirty-seven patients received an ECMES, whereas 3 patients were treated with an external fixator and also 3 fractures were stabilized by plate osteosynthesis. Conservatively treated patients were significantly younger (mean age 6.0) compared to patients treated with ECMES (mean age 10.2) or plate osteosynthesis (PO)/external fixator (EF) (mean age 11.3), even if toddler's fractures (mean age 2.0) are excluded (mean age 7.4). There was no difference in time to full weight-bearing, hospitalization of patients treated with ECMES compared to conservative therapy although ECMES-treated fractures show more instability. The consolidation time was significantly higher in ECMES treated patients compared to conservative therapy.Conclusion: Pediatric patients (≤4 years) with lower leg fractures most often showed simple oblique fractures of the tibia, half of them toddler's fractures, which were treated predominantly by conservative therapy. All in all, the consolidation time was longer in intramedullary nailing (ECMES) than in conservative therapy. Nevertheless, time to full weight bearing and duration of cast was the same in both groups, even though ECMES treated fractures show more instability.
Novel Gross Deletion Mutations in NTRK1 Gene Associated With Congenital Insensitivity to Pain With Anhidrosis
Authors: Li Lulu , Jia Chao , Tang Yue , Kong Yuanyuan , Xia Yaofang , Ma Li 
Published: March 2021

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis, recurrent fever, and intellectual disability. CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). This study aims to identify pathogenic mutations underlying CIPA in two unrelated Chinese families.Methods: DNA was extracted from blood samples of patients and their available family members and subjected to whole exome sequencing (WES). Real-time PCR (qPCR), Gap-PCR, and Sanger sequencing were applied to verify the identified variants.Result: We found novel compound gross deletion mutations [exon1-6 del (g.1-1258_10169del); exon5-7 del (g.6995_11999del)] of NTRK1 (MIM 191315) gene in family 1 and the compound heterozygous mutations [c.851-33T&gt;A; exon5-7 del (g.6995_11999del)] in family 2. Interestingly, we discovered the intragenic novel gross deletion [exon5-7 del (g.6995_11999del)] mediated by recombination between Alu elements.Conclusions: The present study highlights two rare gross deletion mutations in the NTRK1 gene associated with CIPA in two unrelated Chinese families. The deletion of exon1-6 (g.1-1258_10169del) is thought to be the largest NTRK1 deletion reported to date. Our findings expand the mutation spectrum of NTRK1 mutations in the Chinese and could be useful for prenatal interventions and more precise pharmacological treatments to patients. WES conducted in our study is a convenient and useful tool for clinical diagnosis of CIPA and other associated disorders.
Small Molecule Cjoc42 Improves Chemo-Sensitivity and Increases Levels of Tumor Suppressor Proteins in Hepatoblastoma Cells and in Mice by Inhibiting Oncogene Gankyrin
Authors: D’Souza Amber M. , Cast Ashley , Kumbaji Meenasri , Rivas Maria , Gulati Ruhi , Johnston Michael , Smithrud David , Geller James , Timchenko Nikolai 
Published: March 2021

Objective: Relapsed hepatoblastoma (HBL) and upfront hepatocellular carcinoma (HCC) are notoriously chemoresistant tumors associated with poor outcomes. Gankyrin (Gank) is a known oncogene that is overexpressed in pediatric liver cancer and implicated in chemo-resistance. The goal of this study was to evaluate if the Gank-tumor suppressor axis is activated in chemoresistant hepatoblastoma patients and examine if an inhibitor of Gank, Cjoc42, might improve the chemosensitivity of cancer cells.Methods: Expression of Gank and its downstream targets were examined in fresh human HBL samples using immunostaining, QRT-PCR, and Western Blot. Cancer cells, Huh6 (human HBL) and Hepa1c1c7 (mouse HCC) were treated with Cjoc42 and with Cjoc42 in combination with cisplatin or doxorubicin. Cell proliferation, apoptosis, and chemoresistance were examined. To examine activities of Cjoc42 in vivo, mice were treated with different doses of Cjoc42, and biological activities of Gank and cytotoxicity of Cjoc42 were tested.Results: Elevation of Gank and Gank-mediated elimination of TSPs are observed in patients with minimal necrosis after chemotherapy and relapsed disease. The treatment of Huh6 and Hepa1c1c7 with Cjoc42 was not cytotoxic; however, in combination with cisplatin or doxorubicin, Cjoc42 caused a significant increase in cytotoxicity compared to chemotherapy alone with increased apoptosis. Examination of Cjoc42 in WT mice showed that Cjoc42 is well tolerated without systemic toxicity, and levels of tumor suppressors CUGBP1, Rb, p53, C/EBPα, and HNF4α are increased by blocking their Gank-dependent degradation.Conclusions: Our work shows that Cjoc42 might be a promising adjunct to chemotherapy for the treatment of severe pediatric liver cancer and presents mechanisms by which Cjoc42 increases chemo-sensitivity.
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection
Authors: Chen Rui Hong , Yang Li Jun , Hamdoun Sami , Chung Sookja Kim , Lam Christopher Wai-kei , Zhang Kai Xi , Guo Xiaoling , Xia Chenglai , Law Betty Yuen Kwan , Wong Vincent Kam Wai 
Published: March 2021

The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask.
Characterization of Crystalline CsPbBr3 Perovksite Dosimeters for Clinical Radiotherapy
Authors: Bruzzi Mara , Talamonti Cinzia 
Published: March 2021

Lead halide perovskite CsPbBr3 is a wide-gap semiconductor material potentially very attractive for next generations of real-time monitors and particle detectors in high-energy physics. Here, we present the first characterization of crystalline CsPbBr3 point dosimeters with submillimeter size, under 6 MV X-photon beams used in clinical radiotherapy. Current response of the devices proved to be promising in terms of fast rise and decay times, of the same order of the X-ray beam onset and offset ones; absence of polarization effects; reproducibility to repeated irradiations; and linearity of the collected charge as a function of the absorbed dose. Comparing the measured sensitivity with the theoretical one, a charge collection distance of about 100 μm has been evaluated, of the same order of the linear dimensions of crystallites within the samples, suggesting that recombination centers are mainly placed at grain boundaries. A much higher sensitivity per unit area measured with crystalline CsPbBr3 as compared with drop-casted ones can be explained in terms of a less disordered crystalline structure. This work opens the way to CsPbBr3 point dosimeters, with linear dimensions meeting the strict spatial resolution constraints for bidimensional dose mapping required in clinical radiotherapy.
Life Satisfaction, Positive Affect, and Sleep Impairment in Masters Athletes: Modulation by Age, Sex, and Exercise Type
Authors: Wooten Savannah V. , Mittag Uwe , Alvero Cruz José Ramón , Stray-Gundersen Sten , Hoffmann Fabian , Michély Sarah , Möstl Stefan , Sies Wolfram , Mulder Edwin , Rauschendorfer Philipp , Chilibeck Philip D. , Rittweger Jörn , Tanaka Hirofumi 
Published: March 2021

IntroductionThe masters athlete has been proposed as a model of successful aging. Research studies investigating psychological outlook in older athletes have primarily addressed negative affects including depression, anxiety, and stress. The impact of lifelong exercise on positive affect and life satisfaction as well as sleep impairment that could impact on these psychological states is largely unknown.MethodsA series of questionnaires (general life satisfaction, positive affect, and sleep-related impairment) were administered to 240 masters athletes participating in the World Masters Athletics Championships. Total raw scores were converted into T scores for comparison with the general population. Meaningful difference was defined by the PROMIS® as one-half standard deviation from the centering sample.ResultsMeaningful differences were observed for improved general life satisfaction and reduced sleep impairment for all masters athletes. Positive affect did not reach the meaningful difference threshold. No significant sex differences were found for any of the questionnaires (all p &gt; 0.05). Similarly, no significant differences were found between endurance, sprint, and strength/power sports for general life satisfaction (p = 0.18), positive affect (p = 0.46), and sleep impairment (p = 0.77). In general, life satisfaction increased with age (r = 0.15, p = 0.02), and sleep impairment trended towards reduction with age (r = −0.13, p = 0.05). Positive affect demonstrated no correlation with age (r = 0.09, p = 0.18).ConclusionThis study demonstrates that the lifestyles of masters athletes contribute to improved general life satisfaction and reduced sleep impairment but not improved positive affect. The beneficial effects were observed irrespective of age, gender, and sporting types.
The Importance of Nature Exposure and Physical Activity for Psychological Health and Stress Perception: Evidence From the First Lockdown Period During the Coronavirus Pandemic 2020 in France and Germany
Authors: Javelle Florian , Laborde Sylvain , Hosang Thomas Jean , Metcalfe Alan James , Zimmer Philipp 
Published: March 2021

Objective: This cross-sectional questionnaire-based study aims to compare physical activity and nature exposure levels between people living in France and Germany during the lockdown. Furthermore, the secondary aim is to observe the relationship between perceived stress, psychological health, physical activity, and nature exposure in Germany and France during the coronavirus disease 2019 (COVID-19)-related lockdown of April/May 2020.Methods: The study includes 419 participants who have completed the Perceived Stress Scale 10, the World Health Organization Quality of Life-BREF, the Godin-Shephard Leisure-Time Physical Activity Questionnaire, the modified Nature Exposure Scale, and complementary questions related to the lockdown period from April 19 to May 11, 2020. Multiple regression models were constructed to evaluate the relationship of nature exposure and physical exercise with overall stress perception and psychological health in France and Germany when considering a broad range of covariates.Results: Exposure to nature during the lockdown (ηp2 = 0.034, p &lt; 0.001), amount of physical activity ηp2 = 0.014, p &lt; 0.001), and psychological health (ηp2 = 0.041, p &lt; 0.001) were greater in German compared with French participants. Godin Index and Nature Exposure Scale total score were both inversely correlated to stress perception and positively correlated to psychological health. The stress and psychological health regression models explained 10% of the results' variance. Physical activity (Godin Index) was a significant for both models. Nature Exposure Scale total score was a significant predictor only for psychological health. When including all significant covariates, the regression models explained 30.7% for the perceived stress and 42.1% for the psychological health total overall variance.Conclusion: Physical activity and nature exposure are significant predictors of psychological health. Even though both variables are associated with stress perception, only physical activity is a significant predictor of stress perception. Our results suggest that physical activity and nature exposure were key factors to go through the lockdown period in France and Germany.
First demonstration of X-band AlGaN/GaN high electron mobility transistors using free-standing AlN substrate over 15 W mm−1 output power density
Authors: Ozaki Shiro , Yaita Junya , Yamada Atsushi , Kumazaki Yusuke , Minoura Yuichi , Ohki Toshihiro , Okamoto Naoya , Nakamura Norikazu , Kotani Junji 
Published: March 2021

Abstract
In this letter, we successfully achieved high-power radio frequency (RF) operation of AlGaN/GaN high electron mobility transistors (HEMTs) fabricated on free-standing AlN substrate at X-band. The developed HEMT on AlN substrate comprised a 200 nm thick GaN channel and AlGaN buffer with an Al composition of 30%. Thanks to high breakdown voltage of the HEMT on AlN substrate, we successfully demonstrated 15.2 W mm−1 output power density at operating voltages of 70 V even without device technologies such as source-field plate and optimization of device dimension. Our results show that the potential of GaN HEMTs on AlN substrate as next-generation high-power RF devices.