bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthognathic Surgery in Craniosynostosis
Authors: Ferri Joël , Schlund Matthias , Touzet-Roumazeille Sandrine 
Published: October 2020

Introduction:
Craniosynostosis is characterized by the fusion of 1 or more sutures of the skull leading to craniofacial deformations. Our aim is to describe the dental malocclusion associated with craniosynostosis, syndromic, or nonsyndromic, and also the treatment used and its stability.

Material and Methods:
This retrospective study included all patients who presented at our Department for facial growth monitoring and occlusal management following syndromic and nonsyndromic craniosynostosis. Inclusion began in January 1996 and ended in December 2015 to ensure sufficient follow-up. Orthognathic surgery was performed after the end of growth. Dental occlusion was evaluated clinically and radiographically.

Results:
Fifty-five patients were included with 18 syndromic cases. The majority of patients presented with class III malocclusion (69.1%), especially syndromic cases (94.7%) and brachycephalies (96.3%). Conversely, scaphocephalies are associated with class II malocclusions. Thirty-nine patients underwent orthodontic treatment associated with orthognathic surgery to correct their malocclusion. In 4 cases, optimal dental occlusion was achieved with orthodontic treatment alone. Forty patients achieved stable optimal final dental occlusion. Optimal dental occlusion was achieved in 76.9% of the nonsurgically treated craniosynostosis patients and 68.9% of the surgically treated craniosynostosis patients.

Discussion:
Sutural fusion induces a facial growth restrictions and dental malocclusions. Several mechanisms may be responsible for these malocclusions: positional anomaly of the jaws due to the cranial deformity, associated anomaly of the facial sutures, or osteocartilagenous system diseases. Early craniosynostosis management does not avoid the occurrence of malocclusion, which will require orthodontic treatment and orthognathic surgery for their management.
Hyperspace fermions, Möbius transformations, Krein space, fermion doubling, dark matter
Authors: Jaroszkiewicz George 
Published: October 2020

We develop an approach to classical and quantum mechanics where continuous time is extended by an infinitesimal parameter
T
and equations of motion converted into difference equations. These equations are solved and the physical limit
T
→ 0 then taken. In principle, this strategy should recover all standard solutions to the original continuous time differential equations. We find this is valid for bosonic variables whereas with fermions, additional solutions occur. For both bosons and fermions, the difference equations of motion can be related to Möbius transformations in projective geometry. Quantization via Schwinger’s action principle recovers standard particle-antiparticle modes for bosons but in the case of fermions, Hilbert space has to be replaced by Krein space. We discuss possible links with the fermion doubling problem and with dark matter.
An in-depth investigation of the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine
Authors: Pu Jing , Yu Qin , Yin Zhifang , Zhang Ying , Li Xueqi , Li Dandan , Chen Hongbo , Long Runxiang , Zhao Zhimei , Mou Tangwei , Zhao Heng , Feng Shiyin , Xie Zhongping , Wang Lichun , He Zhanlong , Liao Yun , Fan Shengtao , Yin Qiongzhou , Jiang Ruiju , Wang Jianfeng , Zhang Lingli , Li Jing , Zheng Huiwen , Cui Pingfang , Jiang Guorun , Guo Lei , Xu Mingjue , Yang Huijuan , Lu Shan , Wang Xuanyi , Gao Yang , Xu Xingli , Cai Linrui , Zhou Jian , Yu Li , Chen Zhuo , Hong Chao , Du Dan , Zhao Hongling , Li Yan , Ma Kaili , Ma Yunfei , Liu Donglan , Yao Shibao , Li Changgui , Che Yanchun , Liu Longding , Li Qihan 
Published: October 2020

AbstractBACKGROUNDIn-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed.METHODIn a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days.FINDINGIn this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine.INTERPRETATIONIn a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic.Trial registrationNCT04412538FUNDINGThe National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province.
Mental health symptoms in a cohort of hospital healthcare workers following the first peak of the Covid-19 pandemic in the United Kingdom
Authors: Wanigasooriya Kasun , Palimar Priyanka , Naumann David , Ismail Khalida , Fellows Jodie L. , Logan Peter , Thompson Christopher V. , Bermingham Helen , Beggs Andrew D. , Ismail Tariq 
Published: October 2020

AbstractBackgroundThe Covid-19 pandemic is likely to lead to a significant increase in mental health disorders amongst healthcare workers (HCW).AimsWe evaluated the prevalence of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a HCW population in the United Kingdom (UK), to identify subgroups most at risk.MethodsAn electronic survey was conducted between the 05/06/2020 and 31/07/2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations.ResultsThere were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 [IQR: 32-51] years). The prevalence rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5% respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio 2.3 [95% CI 1.9–2.7]; p<0.001), depression (2.5 [2.1–3.0]; p<0.001) and PTSD (2.1 [1.7–2.5]; p<0.001). The availability of adequate personal protective equipment (PPE), wellbeing support and lower exposure to moral dilemmas at work demonstrated significant negative associations with former symptoms (p≤0.001).ConclusionsWe report a high prevalence of clinically significant symptoms of anxiety, depression and PTSD in hospital HCW following the initial Covid-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to wellbeing support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.
Assessment of a Novel Method for Non-invasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome Patients Receiving Inhaled Sedation with Sevoflurane: the ANAISS Study Protocol
Authors: Tronche Pierre-Antoine , Lalande Robin , Blondonnet Raiko , Roszyk Laurence , Zhai Ruoyang , Morand Dominique , Pereira Bruno , Sapin Vincent , Malinovsky Jean-Marc , Mourvillier Bruno , Constantin Jean-Michel , Cousson Joël , Jabaudon Matthieu 
Published: October 2020

ABSTRACTIntroductionRecently, fluid collected from the heat-and-moisture-exchange filters, which are commonly used in most mechanically ventilated patients under intravenous sedation, has been reported as a potential surrogate for fluid in the distal airspace. Therefore, collection of this fluid represents a promising, non-invasive method for sampling the distal airspace in patients with acute respiratory distress syndrome (ARDS) and for facilitating a mechanistic understanding of this devastating disease. The current study protocol was constructed to assess whether this fluid could be sampled from a dedicated device (Anaesthetic Conserving Device [AnaConDa-S], Sedana Medical, Danderyd, Sweden) used to deliver inhaled sevoflurane for sedation in patients with ARDS.Methods and analysisA total of 30 adult patients within 24 hours of meeting the Berlin criteria for moderate-severe ARDS and receiving inhaled sevoflurane as standard sedation in participating centres will be eligible for inclusion into this investigator-initiated, exploratory, prospective, bicentre study. After at least 12 h of inhaled sedation, a sample of directly aspirated, undiluted pulmonary oedema fluid will be collected concurrently with fluid from the AnaConDa-S device. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α and sTNFr-1) and markers of lung endothelial (Ang-2) and epithelial (sRAGE) injury will be measured in both fluids by Multiplex. The primary endpoint is the correlation between protein markers (IL-1β, IL-6, IL-8, TNF-α, sTNFr-1, Ang-2 and sRAGE) measured in the undiluted pulmonary oedema fluid versus the AnaConDa-S fluid.Ethics and disseminationThe study was approved by the appropriate ethics committee (CPP Est I). Informed consent is required. The fluid collection from the AnaConDa-S has potential to foster our understanding of the potential effects of inhaled sedation in clinical ARDS and to open up novel perspectives for prognostic and predictive enrichment in future trials. The results will be published in a peer-reviewed journal.Registration numberNCT03964155.
Experimental Reptarenavirus Infection of Boa constrictor and Python regius
Authors: Hetzel U , Korzyukov Y , Keller S , Szirovicza L , Pesch T , Vapalahti O , Kipar A , Hepojoki J 
Published: October 2020

ABSTRACTBoid inclusion body disease (BIBD) causes losses in captive constrictor snake populations globally. BIBD associates with formation of cytoplasmic inclusion bodies (IB) which mainly comprise reptarenavirus nucleoprotein (NP). In 2017, BIBD was reproduced by cardiac injection of boas and pythons with reptarenaviruses, thus demonstrating a causative link between reptarenavirus infection and the disease. Herein, we report experimental infections of pythons (N=16) and boas (N=16) with three reptarenavirus isolates. First, we used pythons (N=8) to test two virus delivery routes: intraperitoneal injection and tracheal instillation. Independent of the delivery route, we detected viral RNA but no IBs in tissues two weeks post inoculation. Next, we inoculated pythons (N=8) via the trachea. During the four month following the infection snakes showed transient central nervous system (CNS) signs but lacked detectable IB at the time of euthanasia. One of the snakes developed severe CNS signs and we succeeded in re-isolating the virus from the brain of this individual, and could demonstrate viral antigen in neurons. In a third attempt, we tested co-housing, vaccination, and sequential infection with multiple reptarenavirus isolates on boas (N=16). At 10 months post inoculation all except one snake tested positive for viral RNA but none exhibited the characteristic IB. Analysis of the antibody responses demonstrated lower neutralizing but higher anti-reptarenavirus NP titers in experimentally versus naturally reptarenavirus infected boas. Our findings suggest that in addition to reptarenavirus infection, other factors, e.g. the antibody response, contribute to BIBD pathogenesis.IMPORTANCEA 2017 study demonstrated cardiac reptarenavirus injection to induce boid inclusion body disease (BIBD) in pythons and boas. In the present study, we experimentally infected pythons and boas with reptarenavirus via either intraperitoneal injection or tracheal instillation. We found both virus delivery routes to result in infection; though the latter could reflect the natural route of infection. In the experimentally infected snakes, we did not find evidence of inclusion body (IB) formation, characteristic to BIBD, in pythons or in boas. Most of the snakes (11/12) studied were reptarenavirus infected after ten-month follow up, which suggests that they could eventually have developed BIBD. We further found differences between the antibody responses of experimentally and naturally reptarenavirus infected snakes, which could indicate that the pathogenesis of BIBD involves factors additional to reptarenavirus infection. As snakes are poikilotherm, also the housing conditions could have an effect.
Molecular basis forB. pertussisinterference with complement, coagulation, fibrinolytic and contact activation systems: The cryo-EM structure of the Vag8-C1 inhibitor complex
Authors: Dhillon Arun , Deme Justin C. , Furlong Emily , Roem Dorina , Jongerius Ilse , Johnson Steven , Lea Susan M. 
Published: October 2020

AbstractComplement, contact activation, coagulation, and fibrinolysis are serum protein cascades that need strict regulation to maintain human health. Serum glycoprotein, C1-inhibitor (C1-INH) is a key regulator (inhibitor) of serine proteases of all the above-mentioned pathways. Recently, an autotransporter protein, Virulence Associated Gene 8 (Vag8) produced by the whopping cough causing pathogen,Bordetella pertussishas been shown to bind and interfere with C1-INH function. Here we present the structure of Vag8: C1-INH complex determined using cryo-electron microscopy at 3.6 Å resolution. The structure shows a unique mechanism of C1-INH inhibition not employed by other pathogens where Vag8 sequesters the Reactive Centre Loop of the C1-INH preventing its interaction with the target proteases.ImportanceThe structure 105 kDa protein complex is one of the smallest to be determined using cryo-electron microscopy at high resolution. The mechanism of disrupting C1-INH revealed by the structure is crucial to understand how pathogens by producing a single virulence factor can disturb several homeostasis pathways. Virulence mechanisms such as the one described here assume more importance given the emerging evidence about dysregulation of contact activation, coagulation and fibrinolysis leading to COVID-19 pneumonia.
Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility
Authors: Byun Jinyoung , Han Younghun , Li Yafang , Xia Jun , Xiao Xiangjun , Sun Ryan , Walsh Kyle M. , Gorlov Ivan , Gorlova Olga , Zhou Wen , Pettit Rowland W , Song Zhuoyi , Rosenberg Susan M , Zhu Dakai , Wiencke John K. , Albanes Demetrius , Lam Stephan , Tardon Adonina , Chen Chu , Goodman Gary , Bojeson Stig , Brenner Hermann , Landi Maria Teresa , Johansson Mattias , Mulley Thomas , Risch Angela , Wichmann H-Erich , Bickeböller Heike , Christiani David C. , Rennert Gad , Arnold Susanne , Field John K. , Shete Sanjay , LeMarchand Loic , Melander Ole , Brunnstrom Hans , Liu Geoffrey , Andrew Angeline S. , Kiemeney Lambertius A. , Shen Hongbing , Zienolddiny Shan , Grankvist Kjell , Johansson Mikael , Caporaso Neil , Cox Angela , Hong Yun-Chul , Yuan Jian-Min , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Patel Apla , Lan Qing , Rothman Nat , Taylor Fiona , Spitz Margaret , Brennan Paul , Lin Xihong , McKay James , Hung Rayjean J. , Amos Christopher I. ,   INTEGRAL Consortium
Published: October 2020

SummaryLung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequencies across populations; however, comprehensive multi-ethnic analyses may identify variants that are more likely to be causal. This large-scale, multi- ethnic meta-analyses identified 28 novel risk loci achieving genome-wide significance. Leading candidates were further studied using single-cell methods for evaluating DNA-damage. DNA-damage promoting activities were confirmed for selected genes by knockdown genes and overexpression studies.
The smORF-containing genemille-pattesis required for moulting andTrypanosoma cruzimetacyclogenesis in the Chagas disease vectorRhodnius prolixus
Authors: Silva Carina Azevedo Oliveira , da Silveira Alves Sandy , da-Costa-Rodrigues Bruno , Egidio Jonatha Anderson Fraga , Ribeiro Lupis , Logullo Carlos , Mury Flavia Borges , da Silva José Roberto , Nepomuceno-Silva José Luciano , Nunes-da-Fonseca Rodrigo 
Published: October 2020

SummaryChagas disease is estimated to affect 8 million people worldwide and is responsible for circa 10,000 deaths in Latin America every year. Vector control has been developed as the main strategy to control disease spreading. The identification of new targets is essential, and genes containing small open reading frames (smORFs - < 100 amino acids) are present as hundreds of putative new candidate targets in insect genomes. Here, we show that the prototypic smORF containing genemille-pattes/polished-rice/tarsalless(mlpt/pri/tal) is essential for post-embryonic development of the kissing bugRhodnius prolixusand for the metacyclogenesis of theTrypanosoma cruziparasite during nymphal stages. Injection of double-stranded RNA againstmlpt(Rp-dsmlpt) during nymphal stages leads to a plethora of phenotypes which impairs post-embryonic development. First, nymphs of fourth or fifth stage injected with Rp-dsmlptdo not moult. Second, vector digestive physiology is largely modified, and haemozoin is significantly increased in the posterior midgut of Rp-dsmlptnymphs. Third, Rp-mlptknockdown inhibits the metacyclogenesis ofTrypanosoma cruzi, the etiologic agent of Chagas disease. Thus, our study provides the first evidence of a smORF-containing gene regulating vector physiology, parasitic cycle and disease transmission.
Edition of complex gene families in tobacco with GoldenBraid 4.0, a multipurpose web-based platform for plant genome engineering
Authors: Vazquez-Vilar Marta , Garcia-Carpintero Víctor , Selma Sara , Bernabé-Orts Joan M , Sanchez-Vicente Javier , Salazar-Sarasua Blanca , Ressa Arianna , de Paola Carmine , Ajenjo María , Fernández-del-Carmen Asun , Granell Antonio , Orzáez Diego 
Published: October 2020

ABSTRACTCRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy in polyploid crops. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, multiplex constructs comprising tandemly arrayed gRNAs are difficult to assemble, this hampering more widespread use. Here we present a comprehensive upgrade of the popular cloning platform GoldenBraid (GB), in which, on top of its classical multigene cloning software, we integrate new assembly tools for two-dimensions gRNA multiplexing with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the gRNA unspaced approaches, respectively. As functional validation, we show, among others, the assembly of up to 17 tandemly-arrayed gRNAs constructs against a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in tobacco. With these constructs we generated a collection of Cas9-free SPL mutants harboring up to 9 biallelic mutations in a single generation. The functionality of GB-assembled dCas9 and dCas12a-based CRISPR activators and repressors using single and multiplexing gRNAs is also validated. With the incorporation of the new CRISPR tools and part’s collection, GB4.0 turns an unprecedentedly comprehensive open platform for plant genetic engineering.
Proton wires mediate the optical signal for ArcLight-type Genetically Encoded Voltage Indicators
Authors: Kang B.E , Leong L. M. , Kim Y. , Miyazaki K. , Ross W. N. , Baker B. J. 
Published: October 2020

AbstractThe genetically encoded voltage indicators, ArcLight and its derivatives, mediate voltage dependent optical signals by intermolecular, electrostatic interactions between neighboring fluorescent proteins (FPs) via proton wires. A random mutagenesis event placed a negative charge on the exterior of the FP resulting in a greater than 10-fold improvement of the voltage-dependent optical signal. Repositioning this negative charge on the exterior of the FP reversed the polarity of voltage-dependent optical signals suggesting the presence of ‘hot spots’ capable of interacting with the negative charge on a neighboring FP thereby changing the fluorescent output. To explore the potential effect on the chromophore state, voltage-clamp fluorometry was performed with alternating excitation at 390 nm followed by excitation at 470 nm resulting in several mutants exhibiting voltage-dependent, ratiometric optical signals of opposing polarities. However, the kinetics, voltage ranges, and optimal FP fusion sites were different depending on the wavelength of excitation. These results suggest that the FP has external, electrostatic pathways capable of quenching fluorescence that are wavelength specific. ArcLight-derived GEVIs may therefore offer a novel way to map how conditions external to the β-can structure can affect the fluorescence of the chromophore and transiently manipulate those pathways via conformational changes mediated by whole cell voltage clamp.Statement of SignificanceArcLight-type GEVIs utilize proton pathways that send charge information outside of the FP to the internal chromophore enabling voltage induced conformational changes to affect fluorescence. These pathways are excitation wavelength specific suggesting that different external positions affect the protonated and deprotonated states of the chromophore.
Oligomerisation of THAP9 transposase: role of DNA and amino-terminal domains
Authors: Sanghavi Hiral M. , Majumdar Sharmistha 
Published: October 2020

AbstractActive DNA transposases like the Drosophila P element transposase (DmTNP) undergo oligomerisation as a prerequisite for transposition. Human THAP9 (hTHAP9) is a catalytically active but functionally uncharacterised homologue of DmTNP. Here we report (using co-IP, pull down, co-localization, PLA) that both the full length as well as truncated hTHAP9 and DmTNP (corresponding to amino-terminal DNA binding and Leucine-rich coiled coil domains) undergo homo-oligomerisation, predominantly in the nuclei of HEK293T cells. Interestingly, the oligomerisation is shown to be partially mediated by DNA. However, mutating the leucines (either individually or together) or deleting the predicted coiled coil region did not significantly affect oligomerisation. Thus, we highlight the importance of DNA as well as the amino-terminal regions of both hTHAP9 and DmTNP, for their ability to form higher order oligomeric states. We also report that Hcf-1, THAP1, THAP10 and THAP11 are possible protein interaction partners of hTHAP9. These studies lead to several questions about the different putative oligomeric states of hTHAP9 and how they may be related to its yet unknown physiological role as well as interaction partners.