bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further delineation of van den Ende‐Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome
Authors: Hildebrandt Clara C. , Patel Nisha , Graham John M. , Bamshad Michael , Nickerson Deborah A. , White Janson J. , Marvin Colby T. , Miller Danny E. ,   University of Washington Center for Mendelian Genomics, Grand Katheryn L. , Sanchez‐Lara Pedro A. , Schweitzer Daniela , Al‐Zaidan Hamad I. , Al Masseri Zainab , Alkuraya Fowzan S. , Lin Angela E. 
Published: March 2021

AbstractVan den Ende‐Gupta syndrome (VDEGS) is a rare autosomal recessive condition characterized by distinctive facial and skeletal features, and in most affected persons, by biallelic pathogenic variants in SCARF2. We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in SCARF2, 6 (16%) with negative SCARF2 testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in SCARF2 and clinical features of VDEGS. Of the six persons without known pathogenic variants in SCARF2, three remain unsolved despite extensive genetic testing. Three were found to have pathogenic ABL1 variants using whole exome sequencing (WES) or whole genome sequencing (WGS). Their phenotype was consistent with the congenital heart disease and skeletal malformations syndrome (CHDSKM), which has been associated with ABL1 variants. Of the three unsolved cases, two were brothers who underwent WGS and targeted long‐range sequencing of both SCARF2 and ABL1, and the third person who underwent WES and RNA sequencing for SCARF2. Because these affected individuals with classical features of VDEGS lacked a detectable pathogenic SCARF2 variant, genetic heterogeneity is likely. Our study shows the importance of performing genetic testing on individuals with the VDEGS “phenotype,” either as a targeted gene analysis (SCARF2, ABL1) or WES/WGS. Additionally, individuals with the combination of arachnodactyly and blepharophimosis should undergo echocardiography while awaiting results of molecular testing due to the overlapping physical features of VDEGS and CHDSKM.
Early performances of cement paste in the presence of triethanolamine: Rheology, setting and microstructural development
Authors: Lu Zichen , Peng Xinyi , Dorn Tobias , Hirsch Tamino , Stephan Dietmar 
Published: March 2021

AbstractThe effect of triethanolamine (TEA) at various dosages on the early performance of cement paste was systematically evaluated through the techniques of rheological measurements, penetration tests, and ultrasonic pulse velocity. The correlation of early performance to the chemical hydration process was analyzed by calorimetry, zeta potential, in situ XRD, and pore solution analysis. It is found that the effect of TEA on the early performance of cement paste is strongly dependent on its dosage. With the TEA dosage below 0.1 wt%, the setting and microstructural development of cement paste are retarded. Meanwhile, the yield stress of fresh paste is decreased due to the increasing zeta potential of cement grains. The promoted formation of ettringite (AFt) and monosulfate (AFm) caused by TEA decreases the rheological retention ability. At dosages ≥0.2 wt%, the reaction of aluminate‐containing phases is greatly accelerated and a flash setting is observed. Besides, the importance of ferric phase on the reaction of cement with TEA is highlighted. At a low dosage, TEA prefers to accelerate the dissolution of tetracalcium aluminoferrite (C4AF) first and increases the [Fe] in the pore solution of cement paste. In cement without C4AF, the retardation of TEA on silicate phase hydration is significantly alleviated.
Assessment of brain‐to‐blood drug distribution using liquid chromatography
Authors: El Zahar Noha M. , Sutton J. Michael , Bartlett Michael G. 
Published: March 2021

AbstractDelivery of already existing and new drugs under development to the brain necessitates passage across the blood–brain barrier (BBB) with its tight intercellular junctions, molecular components and transporter systems. Consequently, it is critical to identify the extent of brain permeation and the partitioning across the BBB. The interpretation of brain‐to‐blood ratios is considered to be a significant and fundamental approach for estimating drug penetration through BBB, the brain‐targeting ability and central nervous system (CNS) pharmacokinetics. Among the different bioanalytical techniques, liquid chromatography with various detectors has been widely used for determination of these ratios. This review defines the different approaches for sample preparation, extraction techniques and liquid chromatography procedures concerned with the determination of drugs in blood and brain tissues and the assessment of brain‐to‐blood levels. These approaches are expanded to cover the analysis of several drug classes such as CNS‐acting drugs, chemotherapeutics, antidiabetics, herbal medicinal products, radiopharmaceuticals, antibiotics and antivirals. Accordingly, stability in biological matrices and matrix effects are investigated. The different administration/formulation effects and the possible deviations in these ratios are also disscussed.
Optical coherence tomography angiography helps distinguish multiple sclerosis from AQP4‐IgG‐seropositive neuromyelitis optica spectrum disorder
Authors: Liu Chunxin , Xiao Hui , Zhang Xiayin , Zhao Yipeng , Li Rui , Zhong Xiaonan , Wang Yuge , Shu Yaqing , Chang Yanyu , Wang Jingqi , Li Caixia , Lin Haotian , Qiu Wei 
Published: March 2021

AbstractIntroductionThe aim was to characterize the optical coherence tomography (OCT) angiography measures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and to evaluate their disease discrimination capacity.MethodsPatients with MS (n = 83) and AQP4‐IgG‐seropositive NMOSD (n = 91) with or without a history of optic neuritis, together with healthy controls (n = 34), were imaged. The main outcome measures were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell‐inner plexiform layer (GC‐IPL) thickness, macular vessel density (VD), and perfusion density (PD) in the superficial capillary plexus. Diagnostic accuracy was assessed using the area under the receiver operating characteristics curve.ResultsCompared with patients with MS, those with NMOSD had a significantly smaller average thickness of the pRNFL and GC‐IPL (80.0 [59.0; 95.8] μm versus 92.0 [80.2; 101] μm, p < .001; 68.0 [56.0; 81.0] μm, versus 74.5 [64.2; 81.0] μm, p < .001) and significantly smaller whole VD and PD areas (15.6 [12.6; 17.0] mm−1 versus 16.7 [14.8; 17.7] mm−1, p < .001; 0.38 [0.31; 0.42] mm−1 versus 0.40 [0.37; 0.43] mm−1, p < .01). The combination of structural parameters (average thickness of the pRNFL and GC‐IPL) with microvascular parameters (temporal‐inner quadrant of VD, temporal‐inner, nasal‐inferior, and nasal‐outer quadrant of PD) was revealed to have a good diagnostic capability for discriminating between NMOSD and MS.ConclusionsOCT angiography reveals different structural and microvascular retinal changes in MS and AQP4‐IgG‐seropositive NMOSD. These combined structural and microvascular parameters might be promising biomarkers for disease diagnosis.
What drives the adoption and consumption of green hotel products and services? A systematic literature review of past achievement and future promises
Authors: T. M. Arun , Kaur Puneet , Bresciani Stefano , Dhir Amandeep 
Published: March 2021

AbstractThe current study utilises the time‐tested systematic literature review (SLR) method to identify and analyse 76 studies addressing the consumer adoption of green hotels. The results of the research profile analysis show that the literature on consumers' adoption and consumption of green hotel products and services is expanding and gaining more recognition from researchers working in Asian contexts, particularly China, Taiwan and India. Moreover, the qualitative thematic analysis yields four key themes, (a) consumer behaviour variables addressed, (b) antecedents and mediators of green hotel adoption, (c) moderators of the relationship and (d) methodological considerations, for which limitations and future research directions are identified accordingly. The main novelty of the study lies in the development of a unified framework of consumer adoption and consumption of green hotel products and services that calls for a multitheoretic examination of the issue. This review is among the first to consolidate the growing literature on consumer adoption and consumption of green hotel products and services.
Distinct kinetics for nucleotide hydrolysis in lymphocytes isolated from blood, spleen and cervical lymph nodes: Characterization of ectonucleotidase activity
Authors: Doleski Pedro H. , Cabral Fernanda L. , Adefegha Stephen A. , Jantsch Matheus H. , Ebone Renan S. , Leal Daniela B. R. , Schetinger Maria R. C. 
Published: March 2021

AbstractEctonucleotidases are a plasma membrane‐bound enzyme that hydrolyses extracellular adenosine triphosphate (eATP) and adenosine diphosphate (eADP) to adenosine monophosphate (AMP). It regulates normal function of lymphocytes, acts as an inflammatory marker and represents a molecular target for new therapeutics. Thus, this study sought to isolate lymphocytes from blood (BL), spleen (SL) and cervical lymph node (CLL), and characterize the eATP and eADP enzymatic hydrolysis in Wistar rats. The hydrolysis of the nucleotides occurred primarily at pH 8.0, 37°C in the presence of Ca2+ or Mg2+. Chevillard‐plot showed the hydrolysis of eATP and eADP at the same active site. The inhibitors of some classical ATDPases did not cause any significant change on enzymatic activity. Inhibitors of E‐NTPDase (‐1, ‐2, ‐3 isoforms) and E‐NPP‐1 decrease the enzyme activity in all resident lymphocytes. Furthermore, kinetic parameters (Vmax and Km) revealed that SL had significantly (P < .001) higher enzymatic activity when compared to BL and CLL. In conclusion, this study standardized kinetic values for eATP and eADP hydrolysis for resident lymphocytes isolated from BL, SL and CLL.
A Potent N‐(piperidin‐4‐yl)‐1H‐pyrrole‐2‐carboxamide Inhibitor of Adenylyl Cyclase of G. lamblia: Biological Evaluation and Molecular Modelling Studies
Authors: Vega Hissi Esteban G. , De Costa Guardamagna Antonella B. , Garro Adriana D. , Falcon Cristian R. , Anderluh Marko , Tomašič Tihomir , Kikelj Danijel , Yaneff Agustín , Davio Carlos A. , Enriz Ricardo D. , Zurita. Adolfo R. 
Published: March 2021

AbstractIn this work, we report a derivative of N‐(piperidin‐4‐yl)‐1H‐pyrrole‐2‐carboxamide as a new inhibitor for adenylyl cyclase of Giardia lamblia which was obtained from a study using structural data of the nucleotidyl cyclase 1 (gNC1) of this parasite. For such a study, we developed a model for this specific enzyme by using homology techniques, which is the first model reported for gNC1 of G. lamblia. Our studies show that the new inhibitor has a competitive mechanism of action against this enzyme. 2‐Hydroxyestradiol was used as the reference compound for comparative studies. Results in this work are important from two points of view. on the one hand, an experimentally corroborated model for gNC1 of G. lamblia obtained by molecular modelling is presented; on the other hand, the new inhibitor obtained is an undoubtedly excellent starting structure for the development of new metabolic inhibitors for G. lamblia.
The effect of fibroblast growth factor 7 on human dental pulp stem cells for differentiation to AQP5‐positive and αSMA‐positive cells in vitro and in vivo
Authors: Akashi Yoshihiko , Nemoto Atsushi , Nakajima Kei , Kokubun Katsutoshi , Murakami Satoshi , Inoue Takashi , Matsuzaka Kenichi 
Published: March 2021

AbstractObjectivesTransplantation of stem cells into wounds has become popular in regeneration therapies. As stem cells for transplantation, human dental pulp stem cells (hDPSCs) are known to be pluripotent cells that are relatively easy to collect from the pulp of deciduous or wisdom teeth. The purpose of this study was to investigate whether hDPSCs treated with fibroblast growth factor 7 (FGF7) would contribute to the regeneration of wounded rat submandibular glands (SMGs).Materials and methodsIn in vitro studies, hDPSCs were treated with or without FGF7 and mRNA expression levels were examined at days 3, 7 and 14 using qRT‐PCR. The target genes analyzed were BMI1 as an undifferentiated marker, AQP5 as an acinar cell marker, CK19 as a ductal epithelial cell marker, αSMA as a myoepithelial cell marker and VIMENTIN as a fibroblast marker. In in vivo studies, hDPSCs treated with or without FGF7 for 14 days were mixed with type I collagen gels and were transplanted into wounded rat SMGs. Hematoxylin–Eosin and immunohistochemical staining were performed at days 3 and 7, and the numbers of positive cells were counted. The primary antibodies used were against BMI1, AQP5, αSMA, PanCK and VIMENTIN.ResultsIn the in vitro studies, mRNA levels of BMI1 were decreased and αSMA were increased at days 3, 7 and 14, while AQP5 was increased at day 14 in the FGF7 group. In the in vivo studies, the proliferation of hDPSCs and cell islands was observed at day 7 in the FGF7 group. Few BMI1‐positive cells were observed, while numbers of AQP5‐positive and αSMA‐positive cells were increased at days 3 and 7 in the FGF7 group. Moreover, cell islands were AQP5‐positive.ConclusionThese results suggest that FGF7‐treated hDPSCs differentiate into AQP5‐positive and αSMA‐positive cells. Moreover, AQP5‐positive cell aggregations were formed.
Arimistane: Degradation product or metabolite of 7‐oxo‐DHEA?
Authors: Martínez Brito Dayamín , Leogrande Patrizia , Colamonici Cristiana , Curcio Davide , Botre Francesco , de la Torre Xavier 
Published: March 2021

AbstractRationaleThe instability of androst‐5‐ene‐3,7‐dione structures under acidic conditions is known. The formation of arimistane from 7‐oxo‐DHEA, influenced by the conditions of sample extraction, and mainly derivatization reaction and gas chromatography (GC) injector temperature, was described earlier, potentially leading to misinterpretation of results. By using a liquid chromatography (LC)–mass spectrometry (MS) (LC–MS) we investigated the stability of the 7‐oxo‐DHEA in two different solvents (methanol and dimethyl sulfoxide [DMSO]), and the arimistane formation after the application common analytical procedures. Additionally, in vitro and in vivo studies of 7‐oxo‐DHEA were performed.MethodsThe stability of 7‐oxo‐DHEA was studied in solutions after 60 days storage at −20°C. In vitro studies were performed by incubating 7‐oxo‐DHEA with human liver microsomes (HLMs). Healthy volunteers collected urine samples before and after the administration of a single dose of 7‐oxo‐DHEA. Analyses were performed using high‐performance LC (HPLC) coupled to a triple quadrupole mass spectrometer (MS/MS) and GC combustion isotope ratio mass spectrometry (GC‐C‐IRMS) following HPLC purification.Results7‐oxo‐DHEA was stable after 60 days in DMSO while a protic solvent as methanol promotes the degradation of 7‐oxo‐DHEA to arimistane. HLM incubations showed no formation of arimistane and the sample preparation only influenced the degradation of 7‐oxo‐DHEA when solvolysis was applied. After the administration study the presence of arimistane also after the hydrolysis with β‐glucuronidase (Escherichia coli) was observed while using β‐glucuronidase/arylsulfatase (Helix pomatia) showed the presence of arimistane already in blank samples collected before administration.ConclusionsOur results confirm arimistane as a valuable diagnostic marker of 7‐oxo‐DHEA administration, but also indicate that its formation is due to degradation processes rather than to metabolic biotransformation reactions.
Small cats in big trouble? Diet, activity, and habitat use of jungle cats and leopard cats in threatened dry deciduous forests, Cambodia
Authors: Rostro‐García Susana , Kamler Jan F. , Minge Christin , Caragiulo Anthony , Crouthers Rachel , Groenenberg Milou , Gray Thomas N. E. , In Visattha , Pin Chanratana , Sovanna Prum , Kéry Marc , Macdonald David W. 
Published: March 2021

AbstractDry deciduous dipterocarp forests (DDF) cover about 15%–20% of Southeast Asia and are the most threatened forest type in the region. The jungle cat (Felis chaus) is a DDF specialist that occurs only in small isolated populations in Southeast Asia. Despite being one of the rarest felids in the region, almost nothing is known about its ecology. We investigated the ecology of jungle cats and their resource partitioning with the more common leopard cats (Prionailurus bengalensis) in a DDF‐dominated landscape in Srepok Wildlife Sanctuary, Cambodia. We used camera‐trap data collected from 2009 to 2019 and DNA‐confirmed scats to determine the temporal, dietary and spatial overlap between jungle cats and leopard cats. The diet of jungle cats was relatively diverse and consisted of murids (56% biomass consumed), sciurids (15%), hares (Lepus peguensis; 12%), birds (8%), and reptiles (8%), whereas leopard cats had a narrower niche breadth and a diet dominated by smaller prey, primarily murids (73%). Nonetheless, dietary overlap was high because both felid species consumed predominantly small rodents. Both species were primarily nocturnal and had high temporal overlap. Two‐species occupancy modelling suggested jungle cats were restricted to DDF and had low occupancy, whereas leopard cats had higher occupancy and were habitat generalists. Our study confirmed that jungle cats are DDF specialists that likely persist in low numbers due to the harsh conditions of the dry season in this habitat, including annual fires and substantial decreases in small vertebrate prey. The lower occupancy and more diverse diet of jungle cats, together with the broader habitat use of leopard cats, likely facilitated the coexistence of these species. The low occupancy of jungle cats in DDF suggests that protection of large areas of DDF will be required for the long‐term conservation of this rare felid in Southeast Asia.
Upregulation of CCR4 in activated CD8+ T cells indicates enhanced lung homing in patients with severe acute SARS‐CoV‐2 infection
Authors: Spoerl Silvia , Kremer Anita N. , Aigner Michael , Eisenhauer Nina , Koch Pauline , Meretuk Lina , Löffler Patrick , Tenbusch Matthias , Maier Clara , Überla Klaus , Heinzerling Lucie , Frey Benjamin , Lutzny‐Geier Gloria , Winkler Thomas H. , Krönke Gerhard , Vetter Marcel , Bruns Heiko , Neurath Markus F. , Mackensen Andreas , Kremer Andreas E. , Völkl Simon 
Published: March 2021

AbstractCOVID‐19 is a life‐threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood.Comparing the immunological phenotype in healthy donors and patients with mild versus severe COVID‐19 shows that in COVID‐19 patients, NK‐/B‐cell activation and proliferation are enhanced independent of severity. As an important precondition for effective antibody responses, T‐follicular helper cells and antibody secreting cells are increased both in patients with mild and severe SARS‐CoV‐2 infection. Beyond this, T cells in COVID‐19 patients exhibit a stronger activation profile with differentiation toward effector cell phenotypes. Importantly, when looking at the rates of pulmonary complications in COVID‐19 patients, the chemokine receptor CCR4 is higher expressed by both CD4 and CD8 T cells of patients with severe COVID‐19. This raises the hypothesis that CCR4 upregulation on T cells in the pathogenesis of COVID‐19 promotes stronger T‐cell attraction to the lungs leading to increased immune activation with presumably higher pulmonary toxicity.Our study contributes significantly to the understanding of the immunological changes during COVID‐19, as new therapeutic agents, preferentially targeting the immune system, are highly warranted.
Forecasts and decisions: A commentary on Lustick and Tetlock 2021
Authors: Popper Steven W. , Lempert Robert J. , Davis Paul K. , McDonald Tim 
Published: March 2021

AbstractLustick and Tetlock (2021) present a distinctive, persuasive case for theory‐guided simulation and its use in the intelligence community (IC). The usefulness of their insight can be expanded by recognizing the relationship between the forecasting project, the decision‐aiding project, and the knowledge project. We point out further issues for consideration with theory‐guided simulation and the foresight project. We argue that when uncertainty prevails to the extent that forecasting becomes challenged, the real measures of merit should be better decisions, not better predictions. Recent advances in decision‐making under deep uncertainty (DMDU) offer the prospect of providing just such aid to planning and decision. This, in turn, suggests a reconsideration of the IC (and other knowledge project endeavors’) roles in supporting policy deliberations. Potential intersection and cross‐fertilization between DMDU concepts and methods and forecasting technique might prove to be to the mutual benefit of both the forecasting and decision‐aiding projects and transformative to conceptualization of the nature of the knowledge project.
A Pandemic Diary
Authors: Cardwell Mark 
Published: March 2021

AbstractIn mid‐March 2020, The Hastings Center pivoted to work on public health and clinical ethics questions sparked by the Covid‐19 pandemic. The Center created a hub page on our website for ethics resources on the pandemic and published the first in a series of Covid‐19 ethics frameworks for health care providers. The pandemic has illuminated staggering health inequities, particularly for people of color, prompting the Center to launch a series of webinars called Securing Health in a Troubled Time: Equity, Ethics, & the Common Good.
A novel application of superior thyroid artery perforator flaps for medium‐sized intraoral reconstructions: Retrospective analysis of 12 cases
Authors: Ma Chun‐Yue , Guo Bing , Shen Yi , Zheng Zhi‐Wei , Wang Liang , Zhu Dan , Haugen Thorsen W. , Sun Jian 
Published: March 2021

AbstractBackgroundTo describe the indications, technique, and preliminary experience in the application of the superior thyroid artery perforator flap (STAPF) for the reconstruction of various medium‐sized intraoral defects.MethodsFrom September 2018 to September 2019, 12 consecutive cases of oral squamous cell carcinoma underwent reconstruction with a STAPF. Clinical details were collected, and postoperative function was analyzed.ResultsThe venous drainage of the STAPF is variable with drainage into the internal jugular vein in six cases, into both the internal and external jugular veins in four cases, and into the external jugular vein in two cases. Ten cases were harvested as pedicled flaps, while two cases required a venous anastomosis due to inadequate length of the venous pedicle. Ten flaps survived completely, whereas two flaps had partial necrosis that ultimately resolved with secondary healing.ConclusionsSTAPF is a reliable method for the reconstruction of medium‐sized intraoral defects.