bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ras/MAPK dysregulation in development causes a skeletal myopathy in an activating BrafL597V mouse model for cardio‐facio‐cutaneous syndrome
Authors: Maeda Yoshiko , Tidyman William E. , Ander Bradley P. , Pritchard Catrin A. , Rauen Katherine A. 
Published: February 2021

AbstractBackgroundCardio‐facio‐cutaneous (CFC) syndrome is a human multiple congenital anomaly syndrome that is caused by activating heterozygous mutations in either BRAF, MEK1, or MEK2, three protein kinases of the Ras/mitogen‐activated protein kinase (MAPK) pathway. CFC belongs to a group of syndromes known as RASopathies. Skeletal muscle hypotonia is a ubiquitous phenotype of RASopathies, especially in CFC syndrome. To better understand the underlying mechanisms for the skeletal myopathy in CFC, a mouse model with an activating BrafL597V allele was utilized.ResultsThe activating BrafL597V allele resulted in phenotypic alterations in skeletal muscle characterized by a reduction in fiber size which leads to a reduction in muscle size which are functionally weaker. MAPK pathway activation caused inhibition of myofiber differentiation during embryonic myogenesis and global transcriptional dysregulation of developmental pathways. Inhibition in differentiation can be rescued by MEK inhibition.ConclusionsA skeletal myopathy was identified in the CFC BrafL597V mouse validating the use of models to study the effect of Ras/MAPK dysregulation on skeletal myogenesis. RASopathies present a novel opportunity to identify new paradigms of myogenesis and further our understanding of Ras in development. Rescue of the phenotype by inhibitors may help advance the development of therapeutic options for RASopathy patients.
Toll‐like receptor 3 expression in myeloid cells is essential for efficient regeneration after acute pancreatitis in mice
Authors: Hidalgo‐Sastre Ana , Kuebelsbeck Ludwig A. , Jochheim Leonie S. , Staufer Lina M. , Altmayr Felicitas , Johannes Widya , Steiger Katja , Ronderos Monica , Hartmann Daniel , Hüser Norbert , Schmid Roland M. , Holzmann Bernhard , von Figura Guido 
Published: February 2021

AbstractStringent regulation of the inflammatory response is crucial for normal tissue regeneration. Here, we analyzed the role of Toll‐like receptor 3 (TLR3) in pancreatic regeneration after acute pancreatitis (AP). AP was induced by caerulein treatment in mice with global TLR3 deficiency (TLR3OFF) or in mice re‐expressing TLR3 exclusively in the myeloid cell lineage (TLR3Mye). Compared to WT mice, TLR3OFF mice had a markedly increased formation of acinar‐to‐ductal metaplasia (ADM) that persisted until day 7 after initiation of AP. Pancreatic tissue of WT mice was completely regenerated after 5 days with no detectable ADM structures. The enhancing effect of TLR3‐deficiency on ADM formation was closely linked with an increased and prolonged accumulation of macrophages in pancreata of TLR3OFF mice. Importantly, the phenotype of TLR3OFF mice was rescued in TLR3Mye mice, demonstrating the causative role of myeloid cell selective TLR3 signaling. Moreover, in vitro stimulation of macrophages through TLR3 initiated cell death by a caspase‐8‐associated mechanism. Therefore, these findings provide evidence that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after AP. Notably, resolution of inflammation after AP was associated with macrophage sensitivity to TLR3‐mediated cell death.
Strategy for large‐scale monolithic Perovskite/Silicon tandem solar cell: A review of recent progress
Authors: Kim Chan Ul , Jung Eui Dae , Noh Young Wook , Seo Seong Kuk , Choi Yunseong , Park Hyesung , Song Myoung Hoon , Choi Kyoung Jin 
Published: February 2021

AbstractFor any solar cell technology to reach the final mass‐production/commercialization stage, it must meet all technological, economic, and social criteria such as high efficiency, large‐area scalability, long‐term stability, price competitiveness, and environmental friendliness of constituent materials. Until now, various solar cell technologies have been proposed and investigated, but only crystalline silicon, CdTe, and CIGS technologies have overcome the threshold of mass‐production/commercialization. Recently, a perovskite/silicon (PVK/Si) tandem solar cell technology with high efficiency of 29.1% has been reported, which exceeds the theoretical limit of single‐junction solar cells as well as the efficiency of stand‐alone silicon or perovskite solar cells. The International Technology Roadmap for Photovoltaics (ITRPV) predicts that silicon‐based tandem solar cells will account for about 5% market share in 2029 and among various candidates, the combination of silicon and perovskite is the most likely scenario. Here, we classify and review the PVK/Si tandem solar cell technology in terms of homo‐ and hetero‐junction silicon solar cells, the doping type of the bottom silicon cell, and the corresponding so‐called normal and inverted structure of the top perovskite cell, along with mechanical and monolithic tandemization schemes. In particular, we review and discuss the recent advances in manufacturing top perovskite cells using solution and vacuum deposition technology for large‐area scalability and specific issues of recombination layers and top transparent electrodes for large‐area PVK/Si tandem solar cells, which are indispensable for the final commercialization of tandem solar cells.image
Loading rates dependency of strength anisotropy in coal: Based on the three‐dimensional reconstruction modeling technology
Authors: Song Honghua , Zhao Yixin , Wang Jiehao , Jiang Yaodong , Wang Xinzhong 
Published: February 2021

AbstractWe explored the dependency of strength anisotropy on loading rate in coal both experimentally and numerically. An improved numerical modeling method was developed for this investigation to reduce the random error caused by the mechanical differences of coal specimens. After that, specimens with different anisotropy angles (the angle between the coring direction and bedding plane orientation) were processed (0°, 15°, 30°, 45°, 60°, and 90°). These specimens were then scanned by the X‐ray Computed Tomography (CT) and tested by unconfined loading frame. Uniaxial compressive simulations were performed on 15 numerical models with different anisotropy angles at various loading rates (1.0 × 10−6, 5.0 × 10−6, 10.0 × 10−6, and 20.0 × 10−6 mm/step). The results indicate that the uniaxial compressive strength (UCS) of coal generally first decreases and then increases as the anisotropy angle increases from 0° to 90° for all loading rates. It is also found that the UCS increases significantly with the increasing loading rate at anisotropic angles of 30° and 45°, while it is less obvious at anisotropic angles of 0° and 90°. This results in a reduced USC anisotropy at high loading rates. Meanwhile, a negative exponential equation is obtained to describe the variation of UCS with the loading rate at different anisotropic angles. And a unified equation is then developed and verified to define the UCS as a function of the loading rate and anisotropic angle.
Somatic mutation profiles as molecular classifiers of ulcerative colitis‐associated colorectal cancer
Authors: Mäki‐Nevala Satu , Ukwattage Sanjeevi , Olkinuora Alisa , Almusa Henrikki , Ahtiainen Maarit , Ristimäki Ari , Seppälä Toni , Lepistö Anna , Mecklin Jukka‐Pekka , Peltomäki Päivi 
Published: February 2021

AbstractUlcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question by determining the genetic and epigenetic profiles of colitis‐associated colorectal carcinomas (CA‐CRC). The findings were compared to Lynch syndrome (LS), a different form of cancer predisposition that shares the importance of immunological factors in tumorigenesis. CA‐CRCs (n = 27) were investigated for microsatellite instability, CpG island methylator phenotype and somatic mutations of 999 cancer‐relevant genes (“Pan‐cancer” panel). A subpanel of “Pan‐cancer” design (578 genes) was used for LS colorectal tumors (n = 28). Mutational loads and signatures stratified CA‐CRCs into three subgroups: hypermutated microsatellite‐unstable (Group 1, n = 1), hypermutated microsatellite‐stable (Group 2, n = 9) and nonhypermutated microsatellite‐stable (Group 3, n = 17). The Group 1 tumor was the only one with MLH1 promoter hypermethylation and exhibited the mismatch repair deficiency‐associated Signatures 21 and 15. Signatures 30 and 32 characterized Group 2, whereas no prominent single signature existed in Group 3. TP53, the most common mutational target in CA‐CRC (16/27, 59%), was similarly affected in Groups 2 and 3, but DNA repair genes and Wnt signaling genes were mutated significantly more often in Group 2. In LS tumors, the degree of hypermutability exceeded that of the hypermutated CA‐CRC Groups 1 and 2, and somatic mutational profiles and signatures were different. In conclusion, Groups 1 (4%) and 3 (63%) comply with published studies, whereas Group 2 (33%) is novel. The existence of molecularly distinct subgroups within CA‐CRC may guide clinical management, such as therapy options.
Investigating the efficiency of foreign exchange reserves using stochastic frontier analysis: Evidence across the globe
Authors: Agrawal Rachna , Verma Ashima 
Published: February 2021

AbstractThe purpose of this paper is to analyse the efficiency of the use of foreign exchange reserves (FER) by 21 nations over 5 years across the globe. The study follows an analytical research design to analyse the efficiency levels in the use of foreign exchange reserves using stochastic frontier analysis (SFA). Three models under SFA, that is, Cobb–Douglas production frontier for panel data with half‐normal distributions, translog production frontier with panel data assuming truncated normal distributions and total technical efficiency effects model with panel data, have been used to study efficiency levels. The research uses the nominal value of exports and foreign direct investment as inputs and foreign exchange reserves as output. The results indicate that out of 21 nations, developing countries are found to be more efficient in comparison to developed countries in the use of FER.
The presentation and outcomes of Hermansky‐Pudlak syndrome in obstetrics and gynecological settings: A systematic review
Authors: Obeng‐Tuudah Deborah , Hussein Brwa A. , Hakim Amir , Gomez Keith , Abdul Kadir Rezan 
Published: February 2021

AbstractBackgroundHermansky‐Pudlak syndrome (HPS) is a rare autosomal‐recessive disorder with clinical manifestations of bleeding diathesis, multi‐organ disease and variable oculocutaneous albinism (OCA). In women, it can cause life‐threatening obstetric and gynecological (OB/GYN) bleeding.ObjectiveTo summarize OB/GYN presentations, outcomes, and management strategies in women with HPS.Search strategyMain databases (MEDLINE, EMBASE, Cochrane, PubMed, Web of Science Core Collection and Google Scholar) were searched from inception until June 30, 2020.Selection criteriaCase reports/series of women with confirmed HPS.Data collection and analysisA systematic review using PRISMA guidelines. Methodological quality assessment performed using adapted Newcastle Ottawa scale.Main resultsA total 29 pregnancies in 15 women and 2 gynecological patients were identified. Heavy menstrual bleeding (HMB), the most common bleeding symptom, was reported in 8/15 (53%) of women. HMB and post‐partum hemorrhage (PPH) led to diagnosis of HPS in 5/17 (29%) women. Primary PPH was reported in 12/27 (44%) of viable pregnancies; half were major PPH. In 17 pregnancies with known HPS diagnosis, 9 had hemostatic cover with desmopressin and 8 with platelet transfusion. Major PPH occurred in 3/9 (33%) pregnancies covered with desmopressin compared with none in the platelet group.ConclusionDiagnosis of HPS should be considered in women with OCA presenting with HMB or PPH. Hemostatic management options include desmopressin and platelet transfusion. Management should be multidisciplinary with close collaboration between OB/GYN and hematology teams.
Long noncoding RNA CRNDE functions as a diagnostic and prognostic biomarker in osteosarcoma, as well as promotes its progression via inhibition of miR‐335‐3p
Authors: Yu Yali , Wang Leiming , Li Zijun , Zheng Yan , Shi Zhisong , Wang Guanghui 
Published: February 2021

AbstractBackgroundThis study was performed to evaluate the diagnostic and prognostic value, as well as the role of long‐chain noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in osteosarcoma (OS).Materials and MethodsA quantitative real‐time polymerase chain reaction assay was to determine lncRNA CRNDE and microRNA‐335‐3p (miR‐335‐3p) expressions. The Kaplan–Meier analysis was to analyze the relationship between lncRNA CRNDE expression and survival in patients with OS. Receiver operating characteristic curves were to evaluate the diagnostic value of lncRNA CRNDE in OS. Bioinformatics analysis and luciferase reporter assays were used to predict and confirm the relationship between lncRNA CRNDE and miR‐335‐3p. Cell counting Kit‐8 and transwell migration assays assessed the role of lncRNA CRNDE and miR‐335‐3p in OS cells.ResultslncRNA CRNDE expression was upregulated and miR‐355‐3p expression was downregulated in OS. In patients with OS, low lncRNA CRNDE expression demonstrated higher overall survival, whereas high lncRNA CRNDE expression was an independent poor prognostic factor. Furthermore, increased lncRNA CRNDE expression was associated with distant metastasis and the tumor‐node‐metastasis stage in patients with OS, which can be considered as an independent diagnostic biomarker in OS. We revealed that miR‐335‐3p was the target of lncRNA CRNDE. It also demonstrated that knockdown of lncRNA CRNDE inhibited OS cell proliferation, migration, and invasion, and inhibition of miR‐355‐3p promoted this effect. Finally, miR‐335‐3p partially mediated the stimulatory effects of lncRNA CRNDE in OS.ConclusionWe demonstrated that lncRNA CRNDE is a potential diagnostic and prognostic biomarker for OS, and the lncRNA CRNDE/miR‐335‐3p axis participates in OS progression.
Solvent‐free synthesis of compounds containing chromene core catalyzed by novel Brønsted acidic ionic liquids‐ClO4
Authors: Taib Layla A. , Keshavarz Mosadegh , Parhami Abolfath 
Published: February 2021

AbstractA series of novel sulfonic acid‐functionalized Brønsted acidic ionic liquids (BAILs) with perchlorate counter anion are introduced. These ionic liquid catalysts were prepared through simple and eco‐friendly procedures in high yields. Various analytical techniques such as Fourier transform infrared, 1H and 13C NMR, electro‐spray ionization mass spectrometry, elemental analysis (CHNS), and thermogravimetric techniques were used for well characterization of these catalysts. Next, the prepared BAILs were applied as efficient catalysts with high yields under solvent‐free conditions for the synthesis of chromenes. The proposed method offers several superiorities, such as high yields, decreased reaction times, cleaner reactions, and the lack of laborious workup or purification procedures. The simplicity in operation, applicability, and feasibility of this protocol for diverse substrates makes it an efficient alternative to conventional methods.
Methylome and transcriptome profiling revealed epigenetic silencing of LPCAT1 and PCYT1A associated with lipidome alterations in polycystic ovary syndrome
Authors: Mao Zhanrui , Li Ting , Zhao Hui , Wang Xiaoyan , Kang Yixin , Kang Yani 
Published: February 2021

AbstractPolycystic ovary syndrome (PCOS) is the most common endocrine diseases of fertile women and a major cause of infertility. The regulatory effects of DNA methylation on gene transcription and downstream lipid metabolism have not been explored in PCOS. In this study, MBD‐seq and RNA‐seq were performed on ovarian granulosa cells of PCOS patients and controls, and methylation specific PCR and quantitative polymerase chain reaction were used to validate the results. Then lipidomic profiling was conducted on serum of PCOS patients and controls using UPLC‐MS. We identified 73 genes with differently methylated promoters and 830 differently expressed genes. The promoter regions of LPCAT1 and PCYT1A were hypermethylated, accompanied by downregulation of their messenger RNA expression, which may be involved in the regulation of PCOS through downstream glycerophospholipid metabolism and phosphatidylcholine synthesis. The lipid profiling results showed significant changes in 21 lipids, which demonstrated the disturbance in glycerophospholipid metabolism and glycerolipid metabolism pathways. Furthermore, the metabolites‐genes interaction network was constructed to illustrate the association of aberrant methylome and transcriptome with lipidome alterations in glycerolipid and glycerophospholipid metabolism pathways. Our study suggested that the methylation silencing of LPCAT1 and PCYT1A may promote glycerophospholipids metabolism dysregulation, which provided a novel genetic and lipometabolic basis for the pathogenesis of PCOS.
Convergent synthesis of carbonic anhydrase inhibiting bi‐heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition, kinetics, and computational studies
Authors: Khan Farhan M. , Abbasi Muhammad A. , Aziz‐ur‐Rehman  , Siddiqui Sabahat Z. , Sadiq Butt Abdul R. , Raza Hussain , Zafar Ayesha , Ali Shah Syed A. , Shahid Muhammad , Seo Sung‐Yum 
Published: February 2021

AbstractBy using a convergent methodology, a novel series ofN‐arylated 4‐yl‐benzamides containing a bi‐heterocyclic thiazole–triazole core was synthesized, and the structures of these hybrid molecules,9a–k, were corroborated through spectral analyses. The in vitro studies of these multifunctional molecules demonstrated their potent carbonic anhydrase inhibition relative to the standard used. The kinetics mechanism was exposed by Lineweaver–Burk plots, which revealed that9jinhibited carbonic anhydrase non‐competitively by forming an enzyme‐inhibitor complex. The inhibition constants Kicalculated from Dixon plots for this compound was 1.2 μM. The computational study was also persuasive with the experimental results, and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to carbonic anhydrase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for various diseases related to the uncontrolled production of this enzyme.
Effect of pre‐frying on distribution of protons and physicochemical qualities of mackerel
Authors: Zhang Wei , Cheng Shasha , Wang Siqi , Yi Kuan , Sun Shan , Lin Junxin , Tan Mingqian , Li Dongmei 
Published: February 2021

AbstractBACKGROUNDIn this work, low‐field nuclear magnetic resonance (LF‐NMR) and magnetic resonance imaging were used to investigate the changes in protons (from water and oil) distribution of mackerel during the frying process. The relationship between proton migration and some physicochemical indexes was established by partial least squares regression (PLSR). The changing mechanism of the quality characteristics and physicochemical properties of fish meat under different frying conditions was analysed by LF‐NMR combined with PLSR, which provided theoretical support for the development of canned mackerel food.RESULTSLF‐NMR results showed that three kinds of T2 protons assigned to protein–water interaction (T21), multilayer bound water (T22), oil and free water (T23), respectively. As the frying temperature increased, protons from the T22 peak significantly decreased, while protons from the T23 peak remarkably increased. The microstructure of fried mackerel was destroyed; cooking loss, oil content, a* value, b* value, hardness and chewiness increased; and the protein content and L* value decreased. Furthermore, PLSR analysis revealed that significant correlation was observed between the cooking loss, TPA parameter (chewiness), colour parameter (L*) and LF‐NMR parameters.CONCLUSIONDifferent frying temperatures and times had a strong effect on the physicochemical properties of mackerel. Good prediction models could be established by proton migration using the LF‐NMR technique and PLSR for fried mackerel. Quality control of fried fish could be realized by monitoring the change in LF‐NMR data. © 2021 Society of Chemical Industry
Sarcopenia is associated with blood transfusions in head and neck cancer free flap surgery
Authors: Jones Alexander Joseph , Campiti Vincent J. , Alwani Mohamedkazim , Novinger Leah J. , Tucker Brady Jay , Bonetto Andrea , Yesensky Jessica A. , Sim Michael W. , Moore Michael G. , Mantravadi Avinash V. 
Published: February 2021

AbstractObjectiveTo determine if sarcopenia is a predictor of blood transfusion requirements in head and neck cancer free flap reconstruction (HNCFFR).MethodsA single‐institution, retrospective review was performed of HNCFFR patients with preoperative abdominal imaging from 2014 to 2019. Demographics, comorbidities (modified Charlson Comorbidity Index [mCCI]), skeletal muscle index (cm2/m2), oncologic history, intraoperative data, and 30‐day postoperative complications (Clavien‐Dindo score [CD]) were collected. Binary logistic regression was performed to determine predictors of transfusion.ResultsEighty (33.5%), 66 (27.6%), and 110 (46.0%) of n = 239 total patients received an intraoperative, postoperative, or any perioperative blood transfusion, respectively. Sixty‐two (25.9%) patients had sarcopenia. Patients receiving intraoperative transfusions had older age (P = .035), more frequent alcoholism (P = .028) and sarcopenia (P < .001), greater mCCI (P < .001), lower preoperative hemoglobin (P < .001), reconstruction with flaps other than forearm (P = .003), and greater operative times (P = .001), intravenous fluids (P < .001), and estimated blood loss (EBL, P < .001). Postoperative transfusions were associated with major complications (CD ≥ 3; P < .001). Multivariate regression determined sarcopenia (P = .023), mCCI (P = .013), preoperative hemoglobin (P = .002), operative time (P = .036), and EBL (P < .001) as independent predictors of intraoperative transfusion requirements. Postoperative transfusions were predicted by preoperative hemoglobin (P = .007), osseous flap (P = .036), and CD ≥ 3 (P < .001). A perioperative transfusion was predicted by sarcopenia (P = .021), preoperative hemoglobin (P < .001), operative time (P = .008), and CD ≥ 3 (P = .018).ConclusionSarcopenia is associated with increased blood transfusions in HNCFFR. Patients should be counseled preoperatively on the associated risks, and the increased blood product requirement should be accounted in resource‐limited scenarios.Level of Evidence4.