bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine Deaminase Deficiency: From the Discovery of Its Molecular Pathogenesis to Targeted Therapy
Authors: Moretti Federico A , Staal Frank JT 
Published: July 2019

AbstractAdenosine deaminase (ADA) is a key enzyme of the purine metabolism pathway whose gene is located on the chromosome 20 in humans. Mutations in the sequence of theADAgene were found to cause severe combined immunodeficiency (SCID) both in humans and murine disease models.Because of the ubiquitous nature of ADA expression, ADA deficiency should be recognised as a systemic metabolic disorder that results in multiple organ pathologies. However, since the highest ADA expression is observed in the immune cells, the immunologic defects are the most severe clinical symptoms.ADA deficiency has also been the first autosomal recessive immunodeficiency disorder for which the molecular mechanism was identified. This led, consequently, to the development of many different therapies for the management of this disease.Key ConceptsADA‐SCID was the first immunodeficiency for which the molecular mechanism has been identified, thus underscoring the importance of a normal purine metabolism for the development of the immune system.Differences inADAgene expression in various cell types and maturation stages highlight differences in the rate of degradation (activity) of the ADA enzyme and nucleotide metabolism.The evidence that ADA enzyme is highly expressed in lymphoid tissues suggested that lymphocytes have evolved a mechanism to prevent the build‐up of ADA substrates generated by the massive apoptosis and high proliferation rates of these cells.SCIDs are uniformly fatal but have long‐term survival rates if diagnosed early, stabilised and treated before complications arise, such as infections or organ damages.TREC assay is a sensitive and economical alternative test for the diagnosis of ADA deficiency and most other SCIDs.Gene therapy is a genetic engineering technique used to replace a defective gene of a cell in order to prevent a disease.A clinical trial is a research study in which a cohort of patients is prospectively assigned a new therapeutic treatment, that has shown benefits in animals engaged in preclinical trials, but has not yet been proven effective to humans.ADA‐deficient murine models have been extensively used to understand the pathological bases of ADA‐SCID and to test, in preclinical trials, the efficacy and safety of viral vector‐mediated gene therapy and other therapeutic approaches.
Oldowan/Acheulean Succession at Olduvai Gorge
Authors: Proffitt Tomos , Martín‐Ramos Carmen 
Published: July 2019

AbstractThe Acheulean techno‐complex was first identified in 1859 at St Acheul (France) and ever since then, understanding its development has been a prominent area of research within Palaeolithic archaeology. Although the oldest Oldowan and Acheulean are now found in Ethiopia and Kenya; Olduvai Gorge in Tanzania, did, for a long time, provide the earliest examples of both industries, and it still preserves a detailed stratigraphic sequence of Oldowan and Acheulean assemblages. In this sense, Olduvai Gorge has played a central role in exploring the transition from the Oldowan to the Acheulean.Key ConceptsThe Acheulean appears in Kenya at 1.75 Mya.The Acheulean appears in East Africa chronologically after the Oldowan; however, there is a degree of overlap.The Oldowan is typically associated withHomo habilis.The Acheulean is typically associated withHomo ergatser/erectus.Historically, it was suggested that the Oldowan developed into the Acheulean, mirroring hominin evolution.More recently, it is suggested that the Oldowan/Acheulean transition at Olduvai Gorge was a punctuated event associated with the emergence of a new hominin species.
Molecular Genetics of Sorsby Fundus Dystrophy
Authors: Akyol Engin , Lotery Andrew 
Published: July 2019

AbstractSorsby fundus dystrophy (SFD) is a macular dystrophy caused by mutations in the tissue inhibitor metalloproteinase‐3 (TIMP3) gene on chromosome 22. It is a late‐onset autosomal dominant retinal dystrophy. Patients classically develop night blindness and central visual changes and it is often clinically mistaken for wet age‐related macular degeneration (wet AMD). Although SFD often presents at a younger age than wet AMD, it is currently being managed in a similar manner with intravitreal anti‐VEGF. The molecular mechanisms and pathology underlying SFD are not very well understood. Mutations in TIMP3 alter the homeostatic balance of the extracellular matrix as one of the main physiological function of TIMP3 is to inhibit matrix metalloproteinases (MMPs) which are involved in degradation of the ECM.Key ConceptsMutations in tissue inhibitor metalloproteinase‐3 impair extracellular matrix degradation.Sorsby fundus dystrophy can result in choroidal neovascularisation.RPE cells derived from induced pluripotent stem cells (iPSCs) can be used to model Sorsby fundus dystrophy for future studies.Sorsby fundus dystrophy with associated choroidal neovascularisation is currently best managed with anti‐VEGF therapy.There is increased tissue inhibitor metalloproteinase‐3 in the retina of Sorsby fundus dystrophy patients.
Peer support: A needs assessment for social support from trained peers in response to stress among medical physicists
Authors: Johnson Jennifer , Ford Eric , Yu James , Buckey Courtney , Fogh Shannon , Evans Suzanne B. 
Published: July 2019

AbstractPurposePrevious studies suggest that within radiation oncology, medical physicists (MP) experience high workloads. Little is known about how MPs use social support (SS) in times of stress.MethodsIn collaboration with the Workgroup on Prevention of Medical Error, the American Association of Physicists in Medicine administered this Human Investigation Committee (HIC) approved email survey to 8566 members. Respondents were considered likely to seek SS if they answered (probably/definitely would) and unlikely to seek support if they answered (probably/definitely would not). Logistic regression was applied to determine associations between demographic factors and willingness to seek support as well as perception of barriers.ResultsOne thousand two hundred and ninety‐seven members (15.1%) accessed and gave consent for the survey. One thousand and one (11.7%) respondents answered all relevant questions. Respondents were predominantly male (69.1%), MP in radiation oncology (81.8%), private practice (51.6%), with practice duration> 10 yr (60.2%). MPs were likely to seek SS for personal physical illness (78.63%), involvement in a medical error (73.94%) or adverse patient outcome (75.17%). MPs sought SS in the setting of personal fatigue (33.2%) or burnout (44.3%). Barriers to seeking SS were lack of time (80.3%), and uncertainty about whom to access (70.7%). MPs responded that they would be most likely to seek support from an equally experienced medical physicist colleague (81.0%). Most MPs (67.0%) identified as having experienced stressors, with serious family illness (35.2%), or burnout (32.8%) being most common. Factors associated with MPs unwillingness to seek SS for medical error included> 20 yr in practice (vs still in training — OR 0.30, P = 0.015), and male gender (OR 0.60, P = 0.003). Male gender was associated with the lowest willingness to seek support (OR 2.10, P = 0.0001), but also with fewer perceived barriers (OR 1.60, P = 0.0075).ConclusionWillingness to seek SS is demonstrated, and MPs want colleagues to provide support. Given these results, peer support could be considered among MPs.
Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice
Authors: Zhao Guangchao , Deng Jiao , Shen Yuan , Zhang Peng , Dong Hailong , Xie Zhongcong , Xiong Lize 
Published: July 2019

AbstractBackgroundPostoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19–52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood.MethodsWe utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S‐adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested.ResultsPND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S‐adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice.ConclusionsSerum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.
Facile Preparation of High‐Content N‐Doped CNT Microspheres for High‐Performance Lithium Storage
Authors: Wang Jianli , Yan Xufeng , Zhang Zhao , Ying Hangjun , Guo Rongnan , Yang Wentao , Han Wei‐Qiang 
Published: July 2019

AbstractHerein, high‐content N‐doped carbon nanotube (CNT) microspheres (HNCMs) are successfully synthesized through simple spray drying and one‐step pyrolysis. HNCM possesses a hierarchically porous architecture and high‐content N‐doping. In particular, HNCM800 (HNCM pyrolyzed at 800 °C) shows high nitrogen content of 12.43 at%. The porous structure derived from well‐interconnected CNTs not only offers a highly conductive network and blocks diffusion of soluble lithium polysulfides (LiPSs) in physical adsorption, but also allows sufficient sulfur infiltration. The incorporation of N‐rich CNTs provides strong chemical immobilization for LiPSs. As a sulfur host for lithium–sulfur batteries, good rate capability and high cycling stability is achieved for HNCM/S cathodes. Particularly, the HNCM800/S cathode delivers a high capacity of 804 mA h g−1 at 0.5 C after 1000 cycles corresponding to low fading rate (FR) of only 0.011% per cycle. Remarkably, the cathode with high sulfur loading of 6 mg cm−2 still maintains high cyclic stability (capacity of 555 mA h g−1 after 1000 cycles, FR 0.038%). Additionally, CNT/Co3O4 microspheres are obtained by the oxidation of CNTs/Co in the air. The as‐prepared CNT/Co3O4 microspheres are employed as an anode for lithium‐ion batteries and present excellent cycling performance.
Interlayer Topological Transport and Devices Based on Layer Pseudospins in Photonic Valley‐Hall Phases
Authors: Wu Xiaoxiao , Li Zhenyu , Chen Jian , Li Xin , Tian Jingxuan , Huang Yingzhou , Wang Shuxia , Lu Weixin , Hou Bo , Chan Che Ting , Wen Weijia 
Published: July 2019

AbstractValley‐Hall phases, first proposed in 2D materials, originate from nontrivial topologies around valleys which denote local extrema in momentum space. Since they have been extended into classical systems, their designs draw inspirations from existing quantum counterparts, and their transports show similar topological protections. In contrast, it has been recently established in acoustics that layer pseudospins in valley‐Hall phases can give rise to special valley‐Hall edge states with fundamentally different transport behaviors at the interfaces compared with various 2D materials. Their realization in other classical systems, such as photonics, would allow to design topological insulators beyond quantum inspirations. Here, it is shown that layer pseudospins exist in photonic valley‐Hall phases, using vertically coupled designer surface plasmon crystals, a nonradiative system in open environment supporting tightly confined propagating modes. The negligible thermal and radiative losses in the structure pave the way for the direct observations of the layer pseudospins and associated topological phenomena stem from them in both real and reciprocal spaces. Photonic devices that manipulate the signals based on the layer pseudospins of the topological phases, such as layer convertors and layer‐selected delay lines, are experimentally demonstrated, confirming the potential applications of the layer pseudospins as a new degree of freedom carrying information.
Pseudo‐Zn–Air and Zn‐Ion Intercalation Dual Mechanisms to Realize High‐Areal Capacitance and Long‐Life Energy Storage in Aqueous Zn Battery
Authors: Wei Tongye , Li Qian , Yang Gongzheng , Wang Chengxin 
Published: July 2019

AbstractAqueous zinc batteries are considered as promising alternatives to lithium ion batteries owing to their low cost and high safety. However, the developments of state‐of‐the‐art zinc‐ion batteries (ZIB) and zinc–air batteries (ZAB) are limited by the unsatisfied capacities and poor cycling stabilities, respectively. It is of significance in utilizing the long‐cycle life of ZIB and high capacity of ZAB to exploit advanced energy storage systems. Herein, a bulk composite of graphene oxide and vanadium oxide (V5O12·6H2O) as cathode material for aqueous Zn batteries in a mild electrolyte is employed. The battery performance is demonstrated to arise from a combination of the reversible cations insertion/extraction in vanadium oxide and especially the electrochemical redox reactions on the surface functional groups of graphene oxide (named as pseudo‐Zn–air mechanism). Along with adjusting the hydroxyl content on the surface of graphene oxide, the specific capacity is significantly increased from 342 mAh g−1 to a maximum of 496 mAh g−1 at 100 mA g−1. The surface‐controlled kinetics occurring in the bulk composite ensure a high areal capacity of 10.6 mAh cm−2 at a mass loading of 26.5 mg cm−2, and a capacity retention of 84.7% over 10 000 cycles at a high current density of 10 A g−1.
Holoprosencephaly, orofacial cleft, and frontonaso‐orbital encephaloceles: Genetic evaluation of a possible new syndrome
Authors: Richieri‐Costa Antonio , Zechi‐Ceide Roseli M. , Candido‐Souza Rosana M. , Monteiro Rejane A. C. , Tonello Cristiano , de Freitas Mariana L. , Kokitsu‐Nakata Nancy M. , Vendramini‐Pittoli Siulan , Mazzeu Juliana F. , Overes Madelief , Ali‐Amin Roza , van Slegtenhorst Marjon , Hoefsloot Lies H. , Jehee Fernanda S. 
Published: July 2019

AbstractHere we report on a Brazilian child who presented semilobar holoprosencephaly, frontonasal encephaloceles and bilateral cleft lip and palate. Malformations also included agenesis of the corpus callosum, abnormal cortical gyres, dilation of the aqueduct, bilateral endolymphatic sac, bilateral cystic cocci‐vestibular malformation, and a cribriform defect. The 3D TC craniofacial images showed abnormal frontonasal transition region, with a bone bifurcation, and partial agenesis of nasal bone. The trunk and upper and lower limbs were normal. To our knowledge, this rare association of holoprocensephaly with frontonaso‐orbital encephaloceles without limb anomalies has never been reported before. Karyotype was normal. SNP‐array showed no copy‐number alterations but revealed 25% of regions of homozygosity (ROH) with normal copy number, indicating a high coefficient of inbreeding, which significantly increases the risk for an autosomal recessive disorder. Whole exome sequencing analysis did not reveal any pathogenic or likely pathogenic variants. We discuss the possible influence of two variants of uncertain significance found within the patient's ROHs. First, a missense p.(Gly394Ser) in PCSK9, a gene involved in the regulation of plasma low‐density lipoprotein cholesterol. Second, an inframe duplication p.(Ala75_Ala81dup) in SP8, a zinc‐finger transcription factor that regulates signaling centers during craniofacial development. Further studies and/or the identification of other patients with a similar phenotype will help elucidate the genetic etiology of this complex case.
Coronal craniosynostosis due to TCF12 mutations in patients from Turkey
Authors: Yilmaz Elanur , Mihci Ercan , Nur Banu , Alper Ozgul M. 
Published: July 2019

AbstractCraniosynostosis consists of premature fusion of one or more cranial sutures and can be seen as part of a syndrome or diagnosed as nonsyndromic (isolated). Although more than 180 craniosynostosis syndromes have been identified, 70% of the cases are diagnosed as nonsyndromic. On the other hand, genetic causes of the cases are mostly unknown and the overall frequency of the genetic diagnosis is around 25%. In this study, we used targeted Next Generation Sequencing (NGS) analysis to identify the genetic variations of two craniosynostosis cases. We have identified two different truncating mutations, a known NM_207036.1:c.778_779delAT;p.(Met260Valfs*5) and a novel NM_207036.1:c.1102_1108delTCACCTC;p.(Pro369Glnfs*26) TCF12 variants. Additionally, upon physical examination of these two cases, we have observed some shared clinical similarities as well as differences such as bilateral simian crease and hidden cleft palate. This is the first study that reports the TCF12 mutations in Turkish patients with coronal suture synostosis.
Nasal thallium‐201 uptake in patients with parosmia with and without hyposmia after upper respiratory tract infection
Authors: Shiga Hideaki , Okuda Koichi , Taki Junichi , Watanabe Naoto , Tonami Hisao , Kinuya Seigo , Miwa Takaki 
Published: July 2019

BackgroundIn this study, we aimed to determine whether nasal thallium‐201 uptake of the olfactory cleft and olfactory bulb (OB) differs between patients with parosmia with and without hyposmia after upper respiratory tract infection (URTI).MethodsTwenty patients with parosmia after URTI were enrolled in this study (15 women and 5 men, 28 to 76 years old). Nasally administered thallium‐201 migration to the OB, nasal thallium‐201 uptake ratio in the olfactory cleft, and OB volume were determined in 10 patients with normal T&T olfactometry (Daiichi Yakuhin Sangyo, Tokyo, Japan) odor recognition thresholds (≤2.0) who still complained of parosmia (parosmia group), and 10 patients with T&T odor recognition thresholds >2.0 (parosmia and hyposmia group).ResultsThe nasal thallium‐201 uptake ratio in the olfactory cleft was significantly higher in the parosmia group than in the parosmia and hyposmia group (p = 0.0015). Thallium‐201 migration to the OB was not significantly different between the 2 groups (p = 0.31). The OB volume was significantly larger in the parosmia group than that in the parosmia and hyposmia group (p = 0.029); however, the mean OB volume in both the groups was lower than the normal threshold value in healthy individuals.ConclusionOur results signify the recovery of the olfactory epithelium; however, the olfactory neural projections to the OB and regeneration of OB were not complete in patients with parosmia with normal T&T recognition thresholds after URTI.
Crystallization‐Induced Emission of Azobenzene Derivatives
Authors: Yamauchi Mitsuaki , Yokoyama Kosuke , Aratani Naoki , Yamada Hiroko , Masuo Sadahiro 
Published: July 2019

AbstractMost azobenzene derivatives are utilized as well‐defined photoresponsive materials, but their emission properties have not been of great interest as they are relatively poor. Here, we report crystallization‐induced emission (CIE) based on the suppression of the photoisomerization of azobenzene derivatives. Although these molecules show negligible emission in solution, their microcrystals exhibit intense emission from the azobenzene moieties as a result of CIE. Upon rapid precipitation, fine particles with low crystallinity were kinetically formed and underwent CIE over time with a concomitant increase in crystallinity. Furthermore, we demonstrated “photocutting” of an emissive single crystal using a strong laser by a combination of CIE behavior and photomelting based on the photoisomerization of the azobenzene moiety. Our results regarding the CIE behavior of azobenzene derivatives in addition to their photoisomerization can provide a new platform for developing photoresponsive luminescent materials.
Inhibition of paraoxonase 1 by coumarin‐substituted N‐heterocyclic carbene silver(I), ruthenium(II) and palladium(II) complexes
Authors: Karataş Mert Olgun , Çalgın Gamze , Alıcı Bülent , Gökçe Başak , Gençer Nahit , Taşkın Tok Tuğba , Arslan Oktay , Kılıç‐Cıkla Işın , Özdemir Namık 
Published: July 2019

We synthesized three coumarin‐substituted benzimidazolium chlorides and their silver(I), ruthenium(II) and palladium(II) N‐heterocyclic carbene (NHC) complexes. All compounds were characterized using appropriate spectroscopic techniques and elemental analyses. Single‐crystal X‐ray structure of a Pd(II)–NHC complex (6b) was also determined. The inhibitory properties of all compounds were tested on the activity of human paraoxonase 1 (PON1). All complexes exhibited weaker inhibitory properties than their corresponding benzimidazolium salts except for complex 6b which is the most active inhibitor with an IC50 value of 3.01 μM among the compounds reported in this study. A kinetic evaluation showed that this complex inhibits PON1 activity in a non‐competitive manner. Molecular docking studies were also performed for 6b in order to obtain more insight into the binding mode.
Integrating Fetal Therapy Procedures in an Established Labor and Delivery Service
Authors: Kearney Jennifer 
Published: July 2019

AbstractTreating fetal disease in utero is a specialized aspect of obstetric medicine that continues to develop as new technology and better imaging techniques are introduced. Surgical interventions may improve outcomes in fetal diseases such as fetal anemia, spina bifida, and congenital diaphragmatic hernia; however, the addition of a dedicated fetal treatment center to an established busy labor and delivery unit requires facility resources and support. Fetal medicine and labor and delivery leaders can develop a successful fetal therapy service when they partner with fetal medicine specialists, obstetric providers, anesthesia professionals, nursing staff members, and sterile processing department members. By working together, multidisciplinary team members should be able to provide excellent and cost‐effective collaborative care while maintaining patient safety. This article provides an overview of key components that should assist perioperative leaders when developing a successful fetal surgery program.
An Unusual Conversion of 2‐(Alkynonyl)Alkynylbenzenes to Isocoumarins by a Retro‐Favorskii‐like Degradation
Authors: Santhi Jampani , Baire Beeraiah 
Published: July 2019

AbstractWe report the discovery of an anomalous reaction of 2‐(alkynonyl)alkynylbenzenes under AgI catalysis for the selective formation of isocoumarins. This reaction is previously undocumented for 2‐(alkynonyl)alkynylbenzenes in terms of the reaction mechanism and the product formed. Water (H2O18) labeling studies suggested a possible mechanistic pathway in which the initial formation of a pyrylium ion is followed by hydrative dealkynylation, that is, water incorporation and alkyne expulsion, similar to a retro‐Favorskii reaction.
Photo‐Powered Collapse of Supramolecular Polymers Based on an Overcrowded Alkene Switch
Authors: Yu Jing‐Jing , Liang Wen‐Jing , Zhang Qi , Li Ming‐Ming , Qu Da‐Hui 
Published: July 2019

AbstractA supramolecular polymer was constructed from a light‐driven overcrowded alkene switch modified with two alkylated gallic acid amide pendants (MSP‐1). Upon UV irradiation, stable MSP‐1 isomerized into unstable MSP‐2, which induced the effective collapse of well‐defined cross‐linked supramolecular polymers, and the reassembly can be realized by aging at low temperature.