bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Laminin γ2 Proteolytic Fragments in Murine Skin Following Exposure to Sulfur Mustard
Authors: Chang Yoke‐Chen , Wang James D. , Chang Hui‐Ying , Zhou Peihong , Hahn Rita A. , Gordon Marion K. , Laskin Jeffrey D. , Gerecke Donald R. 
Published: May 2020

ABSTRACTLaminin‐332 is a basement membrane protein composed of three genetically distinct polypeptide chains that actively promote both skin epidermal cell adhesion and migration. Proteolytic fragments of the laminin γ2 chain stimulate migration and scattering of keratinocytes and cancer cells. Sulfur mustard (SM) is a bifunctional alkylating agent that induces separation of basal keratinocytes from the dermal‐epidermal junction and invokes a strong inflammatory response leading to delayed wound repair. In the present studies, the role of laminin γ2 in SM‐induced skin injury and wound repair was investigated using the mouse ear vesicant model. We found that laminin γ2 chain mRNA was preferentially upregulated in mouse ear skin exposed to SM. In situ hybridization confirmed overexpression of laminin γ2 transcript. Western blot analysis showed increased protein expression of the full‐length proform of laminin γ2 and smaller processed fragments of laminin γ2 in skin exposed to SM. Dual immunofluorescence labeling indicated that laminin γ2 fragments are prevalent in suprabasal keratinocytes behind the leading edge in areas of hyperplasia in injured skin. In addition, co‐expression of laminin γ2 and the senescent marker, p16−INK4a was found to overlap with the hyperplastic migratory epithelial sheet. This observation is similar to hypermotile keratinocytes reported in invasive carcinoma cells. Overall, our studies indicate that laminin γ2 is preferentially expressed in skin post SM exposure and that protein expression appears to become progressively more fragmented. The laminin γ2 fragments may play a role in regulating SM‐induced skin wound repair. Anat Rec, 2020. © 2020 American Association for Anatomy
Anatomical study of the incisivus labii superioris and inferioris muscles in non‐human primates
Authors: Iwanaga Joe , Watanabe Koichi , Kikuta Shogo , Hirasaki Eishi , Yamaki Koh‐Ichi , Bohm Rudolf P. , Dumont Aaron S. , Tubbs R. Shane 
Published: May 2020

AbstractThe facial muscles have significant roles for vocalization, feeding, and facial expression in both human and non‐human primates. Of these, the anatomy of the incisivus labii superioris (ILS) and incisivus labii inferioris (ILI), which are considered as the accessory bundle of the orbicularis oris (OO) in humans, has rarely been documented in the literature. Our current understanding of the function of the ILS and ILI is that they probably retract the upper and lower lips. Also, there is no account of these muscles in non‐human primates in the current literature. The aim of this study was to reveal the ILS and ILI in non‐human primates. Five Macaca fascicularis, one Macaca fuscata, one Macaca fuscata yakui, and one Pan troglodytes were dissected. Seven formalin‐fixed cadavers and one fresh cadaver were included. Both the ILS and ILI were observed in all specimens. The ILS originated from the incisive fossa of the maxilla and inserted into the OO. The mentalis (MT) and ILI arose from the incisive fossa of the mandible and inserted into the OO and the skin of the chin area. The MT and ILI in the P. troglodytes examined were thicker than in the other three non‐human species, and the ILS and ILI in the three macaques were similar in shape to those of humans. The difference of these muscles may result in different functions of the lip such as during vocalization, feeding, and facial expression.
Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta‐analysis
Authors: Picot Cyndie , Berard Anick , Grenet Guillaume , Ripoche Emmanuelle , Cucherat Michel , Cottin Judith 
Published: May 2020

AbstractOndansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta‐analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case–control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB‐based meta‐analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00–1.23; p < .05; n = 6 studies; I2 = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00–1.49; p < .05; n = 4 studies; I2 = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19–1.84; p < .01; n = 5 studies; I2 = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and “respiratory system anomalies.”
Propensity score methods for time‐dependent cluster confounding
Authors: Cafri Guy , Austin Peter C. 
Published: May 2020

AbstractIn observational studies, subjects are often nested within clusters. In medical studies, patients are often treated by doctors and therefore patients are regarded as nested or clustered within doctors. A concern that arises with clustered data is that cluster‐level characteristics (e.g., characteristics of the doctor) are associated with both treatment selection and patient outcomes, resulting in cluster‐level confounding. Measuring and modeling cluster attributes can be difficult and statistical methods exist to control for all unmeasured cluster characteristics. An assumption of these methods however is that characteristics of the cluster and the effects of those characteristics on the outcome (as well as probability of treatment assignment when using covariate balancing methods) are constant over time. In this paper, we consider methods that relax this assumption and allow for estimation of treatment effects in the presence of unmeasured time‐dependent cluster confounding. The methods are based on matching with the propensity score and incorporate unmeasured time‐specific cluster effects by performing matching within clusters or using fixed‐ or random‐cluster effects in the propensity score model. The methods are illustrated using data to compare the effectiveness of two total hip devices with respect to survival of the device and a simulation study is performed that compares the proposed methods. One method that was found to perform well is matching within surgeon clusters partitioned by time. Considerations in implementing the proposed methods are discussed.
Palbociclib‐letrozole as first‐line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study
Authors: Takahashi Masato , Masuda Norikazu , Nishimura Reiki , Inoue Kenichi , Ohno Shinji , Iwata Hiroji , Hashigaki Satoshi , Muramatsu Yasuaki , Umeyama Yoshiko , Toi Masakazu 
Published: May 2020

AbstractPalbociclib is a highly selective, reversible, oral inhibitor of cyclin‐dependent kinases 4 and 6 that is approved to treat hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer. An open‐label, single‐arm, Japanese phase 2 study was conducted to investigate the efficacy and safety of palbociclib plus letrozole as first‐line treatment in 42 postmenopausal patients with estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer. The probability of progression‐free survival originally reported at 1 year was 75.0% (90% confidence interval, 61.3‐84.4), but median progression‐free survival was not attained at the primary analysis. In this report, updated efficacy and safety results with a longer follow‐up period are presented. The median duration of treatment in the updated analysis was 33.0 months (range, 1.8‐49.2). The probability of progression‐free survival at 1 year was 75.6% (90% confidence interval, 62.4‐84.7). Median progression‐free survival was 35.7 months (95% confidence interval, 21.7‐46.7). Objective response rate and disease control rate were 47.6% (95% confidence interval, 32.0‐63.6) and 85.7% (95% confidence interval, 71.5‐94.6), respectively. Common treatment‐related adverse events (all grades; grade 3/4) were neutropenia (100%; 93%), leukopenia (83%; 60%), and stomatitis (76%; 0%). Treatment‐related febrile neutropenia was reported in one patient. In general, no clinically meaningful deterioration in health‐related quality of life was observed. Palbociclib plus letrozole remained effective and tolerable in Japanese postmenopausal patients with estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer in this updated analysis.
Serine‐227 in the N‐terminal kinase domain of RSK2 is a potential therapeutic target for mantle cell lymphoma
Authors: Matsumura‐Kimoto Yayoi , Tsukamoto Taku , Shimura Yuji , Chinen Yoshiaki , Tanba Kazuna , Kuwahara‐Ota Saeko , Fujibayashi Yuto , Nishiyama Daichi , Isa Reiko , Yamaguchi Junko , Kawaji‐Kanayama Yuka , Kobayashi Tsutomu , Horiike Shigeo , Taniwaki Masafumi , Kuroda Junya 
Published: May 2020

AbstractRSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL), an almost incurable disease subtype of non‐Hodgkin lymphoma. In this study, serine‐227 (RSK2Ser227) in the N‐terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL‐derived cell lines and in tumor tissues derived from five MCL patients. BI‐D1870, an inhibitor specific to RSK2‐NTKD, caused RSK2Ser227 dephosphorylation, and thereby, induced dose‐dependent growth inhibition via G2/M cell cycle blockade and apoptosis in four of the five cell lines, while one cell line showed only modest sensitivity. In addition, RSK2 gene knockdown caused growth inhibition in the four BI‐D1870‐sensitive cell lines. Comparative gene expression profiling of the MCL‐derived cell lines showed that inhibition of RSK2Ser227 by BI‐D1870 caused downregulation of oncogenes, such as c‐MYC and MYB; anti‐apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3, and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B, and BLNK. These findings show that targeting of RSK2Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis. In addition, we found favorable combinatory growth inhibitory effects of BI‐D1870 with inhibitors of BTK (ibrutinib), AKT (ipatasertib), and BCL2 (venetoclax) in cell characteristic‐dependent manners. These results provide a rationale for RSK2Ser227 in the NTKD as a potential therapeutic target in MCL and for future development of a novel bioavailable RSK2 NTKD‐specific inhibitor.
Thoracic aortic disease: Can we safely cover the branches?
Authors: Shatila Wassim , Krajcer Zvonimir 
Published: May 2020

Key Points
Thoracic aortic disease has usually been treated with surgery.
Thoracic endovascular aortic repair is challenging if supra‐aortic vessels are involved.
In situ fenestration of the main graft from a retrograde approach while using bare‐metal stents as bridge stents appears to be a safe and practical technique.
The Robin Hood effect!
Authors: Jolicoeur E. Marc , Henry Timothy D. 
Published: May 2020

Key Points
Results from this analysis support the hypothesis that the reduction of the coronary sinus redistributes coronary flow in the myocardium.
The results from this analysis must be interpreted with caution; while being the first report of its kind, the small sample size and methodological flaws limit the generalizability of the findings.
Future studies should investigate the use of the coronary sinus reducer to improve myocardial function in patients with ischemic cardiomyopathy.
Mechanistic Study on the Selective Oxidation of Acrolein to Acrylic Acid concerning the Role of Water
Authors: Knoche Stefan , Heid Maurice , Gora Niklas , Ohlig Dominik , Drochner Alfons , Etzold Bastian , Vogel Herbert 
Published: May 2020

AbstractThe activity of Mo/V/W mixed oxide catalyst in the gas phase oxidation of acrolein to acrylic acid is tremendously influenced by addition of fed water. This effect of water is investigated and connected to the catalytic mechanism by several stationary kinetic measurements and transient response methods, such as temperature‐programmed reduction, oxidation and desorption experiments, special concentration‐programmed methods as well as H218O‐SSITKA and D2O‐SSITKA experiments. Furthermore, kinetic modeling, based on results of H218O‐SSITKA experiments in a wide temperature and feed water content range gives access to kinetic parameters of single reaction steps in the catalytic mechanism. The developed mechanism is not only able to describe conversion and selectivities, inclusively the effect of water, but also describes the 18O‐degree of labeling of all reaction components quantitatively.
Efficient H2O2 Production via H2O Oxidation on an Anode Modified with Sb‐Containing Mixed Metal Oxides
Authors: Miyase Yuta , Miseki Yugo , Gunji Takahiro , Sayama Kazuhiro 
Published: May 2020

AbstractThe effect of the surface modification of a fluorine‐doped tin oxide (FTO) electrode with an Sb‐containing mixed metal oxide on the oxidative production of H2O2 from H2O was investigated. The initial faradaic efficiency for H2O2 production (FE(H2O2)) reached 98 % when CuSb2Ox/FTO was used as the anode, as a consequence of the suppression of O2 generation via four‐electron oxidation of H2O. InSbOx modification of FTO resulted in a suppression of the oxidative decomposition of H2O2 to O2. The double‐layer composite electrode InSbOx/CuSb2Ox/FTO indicated the advantageous traits of both Sb‐containing mixed metal oxides, and this composite electrode showed superior FE(H2O2), current‐potential dependence, and stability to other electrodes such as CuSb2Ox/FTO, InSbOx/FTO, and Al2O3/BiVO4/FTO.
A hybrid echocardiography‐CFD framework for ventricular flow simulations
Authors: Hedayat Mohammadali , Patel Tatsat R. , Kim Taeouk , Belohlavek Marek , Hoffmann Kenneth R. , Borazjani Iman 
Published: May 2020

AbstractImage‐based CFD is a powerful tool to study cardiovascular flows while 2D echocardiography (echo) is the most widely used noninvasive imaging modality for the diagnosis of heart disease. Here, echo is combined with CFD, that is, an echo‐CFD framework, to study ventricular flows. To achieve this, the previous 3D reconstruction from multiple 2D echo at standard cross sections is extended by: (a) reconstructing aortic and mitral valves from 2D echo and closing the left‐ventricle (LV) geometry by approximating a superior wall; (b) incorporating the physiological assumption of the fixed apex as a reference (fixed) point in the 3D reconstruction; and (c) incorporating several smoothing algorithms to remove the nonphysical oscillations (ringing) near the basal section. The method is applied to echo from a baseline LV and one after inducing acute myocardial ischemia (AMI). The 3D reconstruction is validated by comparing it against a reference reconstruction from many echo sections while flow simulations are validated against the Doppler ultrasound velocity measurements. The sensitivity study shows that the choice of the smoothing algorithm does not change the flow pattern inside the LV. However, the presence of the mitral valve can significantly change the flow pattern during the diastole phase. In addition, the abnormal shape of a LV with AMI can drastically change the flow during diastole. Furthermore, the hemodynamic energy loss, as an indicator of the LV pumping performance, for different test cases is calculated, which shows a larger energy loss for a LV with AMI compared to the baseline one.
Optimal Error Estimates for Analytic Continuation in the Upper Half‐Plane
Authors: Grabovsky Yury , Hovsepyan Narek 
Published: May 2020

AbstractAnalytic functions in the Hardy class H2 over the upper half‐plane ℍ+ are uniquely determined by their values on any curve Γ lying in the interior or on the boundary of ℍ+. The goal of this paper is to provide a sharp quantitative version of this statement. We answer the following question: Given f of a unit H2‐norm that is small on Γ (say, its L2‐norm is of order ϵ), how large can f be at a point z away from the curve? When Γ ⊂ ∂ℍ+, we give a sharp upper bound on ∣f(z)∣ of the form ϵγ, with an explicit exponent γ = γ(z) ∈ (0, 1) and explicit maximizer function attaining the upper bound. When Γ ⊂ ℍ+ we give an implicit sharp upper bound in terms of a solution of an integral equation on Γ. We conjecture and give evidence that this bound also behaves like ϵγ for some γ = γ(z) ∈ (0, 1). These results can also be transplanted to other domains conformally equivalent to the upper half‐plane. © 2020 Wiley Periodicals, Inc.
Construction of an intelligent cellular automata model for historic landscape islands in Shanghai and fusion simulation
Authors: Wei Zhen , Zhang Wei 
Published: May 2020

SummaryHistoric landscape islands are a unique landscape phenomenon in the urbanization and modernization process in Shanghai. Shanghai has been fragmented and isolated at the landscape space level because of islanding, and its historic and cultural values have been broken and weakened. Therefore, it is urgent to implement fusion protection planning. Considering the islanding of urban historic landscape, cellular automata (CA) and neural network intelligent method were used to establish the intelligent CA model of Shanghai historic landscape islands and carry out computer simulation, expecting to provide a basis for studying urban historic landscapes in China via the intelligent evaluation of urban historic landscape islands and the establishment of an intelligent planning model. A technical path to alleviate landscape fragmentation and cultural value fracture of isolated islands was explored, so as to provide the latest theoretical basis for decision makers to manage historic landscape islands in Shanghai and offer reference for more scientific, intelligent, and efficient decision‐making.
Screening for primary immunodeficiency diseases by next‐generation sequencing in early life
Authors: Sun Jinqiao , Yang Lin , Lu Yulan , Wang Huijun , Peng Xiaomin , Dong Xinran , Cheng Guoqiang , Cao Yun , Wu Bingbing , Wang Xiaochuan , Zhou Wenhao 
Published: May 2020

AbstractObjectiveWe aimed to use next‐generation sequencing (NGS) for the early diagnosis of primary immunodeficiency diseases (PIDs) and define its effects on medical management for an infant cohort in early life.MethodsA single‐centre study was conducted from November 2015 to April 2018. Infants less than 3 months old with infections or abnormal white blood cell counts were enrolled in the study. Gene variants were analysed by NGS, and once a mutation was found in a PID‐associated gene, the immune functions associated with this mutation were detected. The diagnosis rate of PIDs in the cohort was the main outcome. The patients received corresponding management and follow‐up treatments.ResultsAmong 2392 patients who were genetically tested with NGS, 51 infants were diagnosed with PIDs. Seven types of PIDs were detected, and the most common (25/51, 49%) were combined immunodeficiencies with associated or syndromic features. Thirty‐five patients (68.6%) were cured or had improved outcomes after being diagnosed with PID. The NGS cost was US$280 per case.ConclusionsThis study not only highlighted the potential of NGS to rapidly deliver molecular diagnoses of PIDs but also indicated that the prevalence of PIDs is underestimated. With broader use, this approach has the potential to alter clinical strategies.
Repurposing current therapeutics for treating COVID‐19: A vital role of prescription records data mining
Authors: Gurwitz David 
Published: May 2020

AbstractSince its outbreak in late 2019, the SARS‐Cov‐2 pandemic already infected over 3.7 million people and claimed more than 250,000 lives globally. At least 1 year may take for an approved vaccine to be in place, and meanwhile millions more could be infected, some with fatal outcome. Over thousand clinical trials with COVID‐19 patients are already listed in ClinicalTrials.com, some of them for assessing the utility of therapeutics approved for other conditions. However, clinical trials take many months, and are typically done with small cohorts. A much faster and by far more efficient method for rapidly identifying approved therapeutics that can be repurposed for treating COVID‐19 patients is data mining their past and current electronic health and prescription records for identifying drugs that may protect infected individuals from severe COVID‐19 symptoms. Examples are discussed for applying health and prescription records for assessing the potential repurposing (repositioning) of angiotensin receptor blockers, estradiol, or antiandrogens for reducing COVID‐19 morbidity and fatalities. Data mining of prescription records of COVID‐19 patients will not cancel the need for conducting controlled clinical trials, but could substantially assist in trial design, drug choice, inclusion and exclusion criteria, and prioritization. This approach requires a strong commitment of health provides for open collaboration with the biomedical research community, as health provides are typically the sole owners of retrospective drug prescription records.
Deletion of c16orf45 in zebrafish results in a low fertilization rate and increased thigmotaxis
Authors: Li Tingting , Li Fei , Lin Jia , Zhang Yinglan , Zhang Qi , Sun Yanhe , Chen Xudong , Xu Mingqing , Wang Xu , Li Qiang 
Published: May 2020

Abstractc16orf45 is located at 16p13.11, an important locus related to neurodevelopmental diseases. Clinical studies have demonstrated that c16orf45 is associated with various neurodevelopmental diseases. To further elucidate the effect of c16orf45 on neural development, we constructed a zebrafish model with a stably inherited c16orf45 deletion via CRISPR/Cas9 technology. We found that deletion of c16orf45 significantly reduced the zebrafish fertilization rate, and both females and males showed reduced fertility. Meanwhile, the homozygous c16orf45 knockout zebrafish showed a developmental delay at 24 hr postfertilization (hpf). However, morphological changes were not apparent after 2 days postfertilization (dpf). Notably, the results of behavioral experiments revealed increased thigmotaxis in c16orf45−/− zebrafish at 2 months. In conclusion, these findings demonstrate that c16orf45 plays an important role in nervous system and reproductive system.