bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-30d suppresses proliferation and invasiveness of pancreatic cancer by targeting the SOX4/PI3K-AKT axis and predicts poor outcome
Authors: Xu Xiaodong , Zong Ke , Wang Xinxing , Dou Dongwei , Lv Pengwei , Zhang Zhe , Li Hongwen
Published: April 2021

Aberrant expression of miR-30d is associated with the development and progression of several human cancers. However, its biological roles and underlying mechanisms in pancreatic cancer are largely unknown. The expression of miR-30d in pancreatic cancer was evaluated in public databases and further valuated by real-time quantitative PCR, western blot, and immunohistochemistry in a cohort of pancreatic cancer patients. The role of miR-30d in the proliferation and metastasis of pancreatic cancer cells was determined using in vitro and in vivo assays. Bioinformatics analyses were performed to examine potential target genes of miR-30d. Luciferase reporter assay and functional rescue experiments were used to elucidate the mechanisms of miR-30d. miR-30d was found frequently decreased in pancreatic cancer compared with nontumor tissues, and downregulation of miR-30d predicted poor prognosis and early relapse of pancreatic cancer patients. Overexpression of miR-30d significantly repressed the growth and metastasis of pancreatic cancer cells both in vitro and in vivo. Bioinformatics analyses identified sex-determining region Y-box 4 (SOX4) as a target gene of miR-30d. Mechanically, miR-30d exerted its tumor suppressive effect by directly targeting SOX4, which caused inhibition of the PI3K-AKT signaling pathway. Overexpression of SOX4 partially antagonized the inhibitory effects of miR-30d. Our study demonstrated that dysregulation of the miR-30d/SOX4/PI3K-AKT axis promotes the development and progression of pancreatic cancer. These findings suggest miR-30d as a promising and reliable therapeutic target for pancreatic cancer.
TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway
Authors: Xiong Yanlu , Feng Yangbo , Zhao Jinbo , Lei Jie , Qiao Tianyun , Zhou Yongsheng , Lu Qiang , Jiang Tao , Jia Lintao , Han Yong
Published: April 2021

Transcription factor AP-2α (TFAP2A) was previously regarded as a critical regulator during embryonic development, and its mediation in carcinogenesis has received intensive attention recently. However, its role in lung adenocarcinoma (LUAD) has not been fully elucidated. Here, we tried to investigate TFAP2A expression profiling, clinical significance, biological function and molecular underpinnings in LUAD. We proved LUAD possessed universal TFAP2A high expression, indicating a pervasively poorer prognosis in multiple independent datasets. Then we found TFAP2A was not indispensable for LUAD proliferation, and exogenous overexpression even caused repression. However, we found TFAP2A could potently promote LUAD metastasis possibly by triggering epithelial–mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated TFAP2A could transactivate Pregnancy-specific glycoprotein 9 (PSG9) to enhance transforming growth factor β (TGF-β)-triggering EMT in LUAD. Meanwhile, we discovered suppressed post-transcriptional silencing of miR-16 family upon TFAP2A partly contributed to TFAP2A upregulation in LUAD. In clinical specimens, we also validated cancer-regulating effect of miR-16 family/TFAP2A/PSG9 axis, especially for lymph node metastasis of LUAD. In conclusion, we demonstrated that TFAP2A could pivotally facilitate LUAD progression, possibly through a novel pro-metastasis signaling pathway (miR-16 family/TFAP2A/PSG9/ TGF-β).
Development of a bispecific immune engager using a recombinant malaria protein
Authors: Nordmaj Mie A. , Roberts Morgan E. , Sachse Emilie S. , Dagil Robert , Andersen Anne Poder , Skeltved Nanna , Grunddal Kaare V. , Erdoğan Sayit Mahmut , Choudhary Swati , Gustsavsson Tobias , Ørum-Madsen Maj Sofie , Moskalev Igor , Tian Weihua , Yang Zhang , Clausen Thomas M. , Theander Thor G. , Daugaard Mads , Nielsen Morten A. , Salanti Ali
Published: April 2021

As an immune evasion and survival strategy, thePlasmodium falciparummalaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.
Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression
Authors: Gu Xiaoguang , Zhang Jianan , Ran Yajuan , Pan Hena , Jia JinHong , Zhao Ying , Zhao Xijuan , Li Wendi , Song Shasha , Yu Xiufeng
Published: April 2021

Circular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.
C3G downregulation induces the acquisition of a mesenchymal phenotype that enhances aggressiveness of glioblastoma cells
Authors: Manzano Sara , Gutierrez-Uzquiza Alvaro , Bragado Paloma , Sequera Celia , Herranz Óscar , Rodrigo-Faus María , Jauregui Patricia , Morgner Stephanie , Rubio Ignacio , Guerrero Carmen , Porras Almudena
Published: April 2021

Glioblastoma (GBM) is the most aggressive tumor from the central nervous system (CNS). The current lack of efficient therapies makes essential to find new treatment strategies. C3G, a guanine nucleotide exchange factor for some Ras proteins, plays a dual role in cancer, but its function in GBM remains unknown. Database analyses revealed a reduced C3G mRNA expression in GBM patient samples. C3G protein levels were also decreased in a panel of human GBM cell lines as compared to astrocytes. Based on this, we characterized C3G function in GBM using in vitro and in vivo human GBM models. We report here that C3G downregulation promoted the acquisition of a more mesenchymal phenotype that enhanced the migratory and invasive capacity of GBM cells. This facilitates foci formation in anchorage-dependent and -independent growth assays and the generation of larger tumors in xenografts and chick chorioallantoic membrane (CAM) assays, but with a lower cell density, as proliferation was reduced. Mechanistically, C3G knock-down impairs EGFR signaling by reducing cell surface EGFR through recycling inhibition, while upregulating the activation of several other receptor tyrosine kinases (RTKs) that might promote invasion. In particular, FGF2, likely acting through FGFR1, promoted invasion of C3G-silenced GBM cells. Moreover, ERKs mediate this invasiveness, both in response to FGF2- and serum-induced chemoattraction. In conclusion, our data show the distinct dependency of GBM tumors on C3G for EGF/EGFR signaling versus other RTKs, suggesting that assessing C3G levels may discriminate GBM patient responders to different RTK inhibition protocols. Hence, patients with a low C3G expression might not respond to EGFR inhibitors.
Synergistic effect of the TLR5 agonist CBLB502 and its downstream effector IL-22 against liver injury
Authors: Melin Nicolas , Sánchez-Taltavull Daniel , Fahrner René , Keogh Adrian , Dosch Michel , Büchi Isabel , Zimmer Yitzhak , Medová Michaela , Beldi Guido , Aebersold Daniel M. , Candinas Daniel , Stroka Deborah
Published: April 2021

The toll-like receptor 5 (TLR5) agonist, CBLB502/Entolimod, is a peptide derived from bacterial flagellin and has been shown to protect against radiation-induced tissue damage in animal models. Here we investigated the protective mechanism of CBLB502 in the liver using models of ischemia-reperfusion injury and concanavalin A (ConA) induced immuno-hepatitis. We report that pretreatment of mice with CBLB502 provoked a concomitant activation of NF-κB and STAT3 signaling in the liver and reduced hepatic damage in both models. To understand the underlying mechanism, we screened for cytokines in the serum of CBLB502 treated animals and detected high levels of IL-22. There was no transcriptional upregulation of IL-22 in the liver, rather it was found in extrahepatic tissues, mainly the colon, mesenteric lymph nodes (MLN), and spleen. RNA-seq analysis on isolated hepatocytes demonstrated that the concomitant activation of NF-κB signaling by CBLB502 and STAT3 signaling by IL-22 produced a synergistic cytoprotective transcriptional signature. In IL-22 knockout mice, the loss of IL-22 resulted in a decrease of hepatic STAT3 activation, a reduction in the cytoprotective signature, and a loss of hepatoprotection following ischemia-reperfusion-induced liver injury. Taken together, these findings suggest that CBLB502 protects the liver by increasing hepatocyte resistance to acute liver injury through the cooperation of TLR5-NF-κB and IL-22-STAT3 signaling pathways.
MCPIP1-mediated NFIC alternative splicing inhibits proliferation of triple-negative breast cancer via cyclin D1-Rb-E2F1 axis
Authors: Chen Fengxia , Wang Qingqing , Yu Xiaoyan , Yang Ningning , Wang Yuan , Zeng Yangyang , Zheng Zhewen , Zhou Fuxiang , Zhou Yunfeng
Published: April 2021

Triple-negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis and the highest metastatic and recurrence potential, which represents 15–20% of all breast cancers in Chinese females, and the 5-year overall survival rate is about 80% in Chinese women. Recently, emerging evidence suggested that aberrant alternative splicing (AS) plays a crucial role in tumorigenesis and progression. AS is generally controlled by AS-associated RNA binding proteins (RBPs). Monocyte chemotactic protein induced protein 1 (MCPIP1), a zinc finger RBP, functions as a tumor suppressor in many cancers. Here, we showed that MCPIP1 was downregulated in 80 TNBC tissues and five TNBC cell lines compared to adjacent paracancerous tissues and one human immortalized breast epithelial cell line, while its high expression levels were associated with increased overall survival in TNBC patients. We demonstrated that MCPIP1 overexpression dramatically suppressed cell cycle progression and proliferation of TNBC cells in vitro and repressed tumor growth in vivo. Mechanistically, MCPIP1 was first demonstrated to act as a splicing factor to regulate AS in TNBC cells. Furthermore, we demonstrated that MCPIP1 modulated NFIC AS to promote CTF5 synthesis, which acted as a negative regulator in TNBC cells. Subsequently, we showed that CTF5 participated in MCPIP1-mediated antiproliferative effect by transcriptionally repressing cyclin D1 expression, as well as downregulating its downstream signaling targets p-Rb and E2F1. Conclusively, our findings provided novel insights into the anti-oncogenic mechanism of MCPIP1, suggesting that MCPIP1 could serve as an alternative treatment target in TNBC.
Correction: Abrogation of store-operated Ca2+ entry protects against crystal-induced ER stress in human proximal tubular cells
Authors: Gombedza Farai C. , Shin Samuel , Kanaras Yianni L. , Bandyopadhyay Bidhan C.
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41420-021-00445-9
Lgals3bp suppresses colon inflammation and tumorigenesis through the downregulation of TAK1-NF-κB signaling
Authors: Cho Sang-Hee , Shim Hyun-Jeong , Park Mi-Ra , Choi Ji-Na , Akanda Md Rashedunnabi , Hwang Jun-Eul , Bae Woo-Kyun , Lee Kyung-Hwa , Sun Eun-Gene , Chung Ik-Joo
Published: April 2021

Galectin 3-binding protein (LGALS3BP, also known as 90K) is a multifunctional glycoprotein involved in immunity and cancer. However, its precise role in colon inflammation and tumorigenesis remains unclear. Here, we showed that Lgals3bp−/− mice were highly susceptible to colitis and colon tumorigenesis, accompanied by the induction of inflammatory responses. In acute colitis, NF-κB was highly activated in the colon of Lgals3bp−/− mice, leading to the excessive production of pro-inflammatory cytokines, such as IL-6, TNFα, and IL-1β. Mechanistically, Lgals3bp suppressed NF-κB through the downregulation of TAK1 in colon epithelial cells. There was no significant difference in the pro-inflammatory cytokine levels between wild-type and Lgals3bp−/− mice in a chronic inflammatory state, during colon tumorigenesis. Instead, Lgals3bp−/− mice showed elevated levels of GM-CSF, compared to those in WT mice. We also found that GM-CSF promoted the accumulation of myeloid-derived suppressor cells and ultimately increased colon tumorigenesis in Lgals3bp−/− mice. Taken together, Lgals3bp plays a critical role in the suppression of colitis and colon tumorigenesis through the downregulation of the TAK1-NF-κB-cytokine axis. These findings suggest that LGALS3BP is a novel immunotherapeutic target for colon inflammation and tumorigenesis.
Tubulin acetylation enhances lung cancer resistance to paclitaxel-induced cell death through Mcl-1 stabilization
Authors: Wattanathamsan Onsurang , Thararattanobon Rawikorn , Rodsiri Ratchanee , Chanvorachote Pithi , Vinayanuwattikun Chanida , Pongrakhananon Varisa
Published: April 2021

The posttranslational modifications (PTMs) of microtubules have been reported to play an important role in cancer aggressiveness, including apoptosis resistance. In this study, we aimed to investigate the biological role of microtubule PTMs in the regulation of paclitaxel responsiveness. The acetylated tubulin (Ace-tub) level was strongly associated with paclitaxel sensitivity, as observed in patient-derived primary lung cancer cells and xenografted immunodeficient mice. We showed that paclitaxel-resistant H460 lung cancer cells, generated by a stepwise increase in paclitaxel, exhibited markedly increased tubulin acetylation and consequently acquired paclitaxel resistance. Upregulation of tubulin acetylation by overexpression of α-tubulin acetyltransferase 1 wild-type (αTAT1wt), an enzyme required for acetylation, or by treatment with trichostatin A (TSA), a histone deacetylase 6 (HDAC6) inhibitor, significantly attenuated paclitaxel-induced apoptosis. Investigation of the underlying mechanism revealed that the levels of antiapoptotic Mcl-1 appeared to increase in αTAT1wt-overexpressing and TSA-treated cells compared to control cells, whereas the levels of other antiapoptotic regulatory proteins were unchanged. On the other hand, decreased tubulin acetylation by αTAT1 RNA interference downregulated Mcl-1 expression in patient-derived primary lung cancer and paclitaxel-resistant lung cancer cells. A microtubule sedimentation assay demonstrated that Mcl-1 binds to microtubules preferentially at Ace-type, which prolongs the Mcl-1 half-life (T1/2). Furthermore, immunoprecipitation analysis revealed that polyubiquitination of Mcl-1 was extensively decreased in response to TSA treatment. These data indicate that tubulin acetylation enhances the resistance to paclitaxel-induced cell death by stabilizing Mcl-1 and protecting it from ubiquitin–proteasome-mediated degradation.
The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase
Authors: Aubi Oscar , Prestegård Karina S. , Jung-KC Kunwar , Shi Tie-Jun Sten , Ying Ming , Grindheim Ann Kari , Scherer Tanja , Ulvik Arve , McCann Adrian , Spriet Endy , Thöny Beat , Martinez Aurora
Published: April 2021

Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. A homozygous Pah-R261Q mouse, with a highly prevalent misfolding variant in humans, reveals the expected hepatic PAH activity decrease, systemic L-Phe increase, L-tyrosine and L-tryptophan decrease, and tetrahydrobiopterin-responsive hyperphenylalaninemia. Pah-R261Q mice also present unexpected traits, including altered lipid metabolism, reduction of liver tetrahydrobiopterin content, and a metabolic profile indicative of oxidative stress. Pah-R261Q hepatic tissue exhibits large ubiquitin-positive, amyloid-like oligomeric aggregates of mutant PAH that colocalize with selective autophagy markers. Together, these findings reveal that PKU, customarily considered a loss-of-function disorder, can also have toxic gain-of-function contribution from protein misfolding and aggregation. The proteostasis defect and concomitant oxidative stress may explain the prevalence of comorbid conditions in adult PKU patients, placing this mouse model in an advantageous position for the discovery of mutation-specific biomarkers and therapies.
Limits to visual representational correspondence between convolutional neural networks and the human brain
Authors: Xu Yaoda , Vaziri-Pashkam Maryam
Published: April 2021

Convolutional neural networks (CNNs) are increasingly used to model human vision due to their high object categorization capabilities and general correspondence with human brain responses. Here we evaluate the performance of 14 different CNNs compared with human fMRI responses to natural and artificial images using representational similarity analysis. Despite the presence of some CNN-brain correspondence and CNNs’ impressive ability to fully capture lower level visual representation of real-world objects, we show that CNNs do not fully capture higher level visual representations of real-world objects, nor those of artificial objects, either at lower or higher levels of visual representations. The latter is particularly critical, as the processing of both real-world and artificial visual stimuli engages the same neural circuits. We report similar results regardless of differences in CNN architecture, training, or the presence of recurrent processing. This indicates some fundamental differences exist in how the brain and CNNs represent visual information.
Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase
Authors: Azadmanesh Jahaun , Lutz William E. , Coates Leighton , Weiss Kevin L. , Borgstahl Gloria E. O.
Published: April 2021

Human manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to rid the mitochondria of O2•−. The mechanisms of concerted transfer enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules at particular redox states. Here, neutron diffraction of two redox-controlled manganese superoxide dismutase crystals reveal the all-atom structures of Mn3+ and Mn2+ enzyme forms. The structures deliver direct data on protonation changes between oxidation states of the metal. Observations include glutamine deprotonation, the involvement of tyrosine and histidine with altered pKas, and four unusual strong-short hydrogen bonds, including a low barrier hydrogen bond. We report a concerted proton and electron transfer mechanism for human manganese superoxide dismutase from the direct visualization of active site protons in Mn3+ and Mn2+ redox states.
Benzylic C−H acylation by cooperative NHC and photoredox catalysis
Authors: Meng Qing-Yuan , Lezius Lena , Studer Armido
Published: April 2021

Methods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.
Robustness and plasticity in Drosophila heat avoidance
Authors: Simões José Miguel , Levy Joshua I. , Zaharieva Emanuela E. , Vinson Leah T. , Zhao Peixiong , Alpert Michael H. , Kath William L. , Para Alessia , Gallio Marco
Published: April 2021

Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°–1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a “Braitenberg vehicle”) which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior.
Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling
Authors: Brunt Lucy , Greicius Gediminas , Rogers Sally , Evans Benjamin D. , Virshup David M. , Wedgwood Kyle C. A. , Scholpp Steffen
Published: April 2021

Wnt signaling regulates cell proliferation and cell differentiation as well as migration and polarity during development. However, it is still unclear how the Wnt ligand distribution is precisely controlled to fulfil these functions. Here, we show that the planar cell polarity protein Vangl2 regulates the distribution of Wnt by cytonemes. In zebrafish epiblast cells, mouse intestinal telocytes and human gastric cancer cells, Vangl2 activation generates extremely long cytonemes, which branch and deliver Wnt protein to multiple cells. The Vangl2-activated cytonemes increase Wnt/β-catenin signaling in the surrounding cells. Concordantly, Vangl2 inhibition causes fewer and shorter cytonemes to be formed and reduces paracrine Wnt/β-catenin signaling. A mathematical model simulating these Vangl2 functions on cytonemes in zebrafish gastrulation predicts a shift of the signaling gradient, altered tissue patterning, and a loss of tissue domain sharpness. We confirmed these predictions during anteroposterior patterning in the zebrafish neural plate. In summary, we demonstrate that Vangl2 is fundamental to paracrine Wnt/β-catenin signaling by controlling cytoneme behaviour.
Electronic structure of aqueous two-dimensional photocatalyst
Authors: Kang Dawei , Kong Xianghua , Michaud-Rioux Vincent , Chen Ying-Chih , Mi Zetian , Guo Hong
Published: April 2021

The electronic structure, in particular the band edge position, of photocatalyst in presence of water is critical for photocatalytic water splitting. We propose a direct and systematic density functional theory (DFT) scheme to quantitatively predict band edge shifts and their microscopic origins for aqueous 2D photocatalyst, where thousands of atoms or more are able to be involved. This scheme is indispensable to correctly calculate the electronic structure of 2D photocatalyst in the presence of water, which is demonstrated in aqueous MoS2, GaS, InSe, GaSe and InS. It is found that the band edge of 2D photocatalysts are not rigidly shifted due to water as reported in previous studies of aqueous systems. Specifically, the CBM shift is quantitatively explained by geometric deformation, water dipole and charge redistribution effect while the fourth effect, i.e., interfacial chemical contact, is revealed in the VBM shift. Moreover, the revealed upshift of CBM in aqueous MoS2should thermodynamically help carriers to participate in hydrogen evolution reaction (HER), which underpin the reported experimental findings that MoS2is an efficient HER photocatalyst. Our work paves the way to design 2D materials in general as low-cost and high-efficiency photocatalysts.
Assortative social mixing and sex disparities in tuberculosis burden
Authors: Shaweno Debebe , Horton Katherine C. , Hayes Richard J. , Dodd Peter J.
Published: April 2021

Globally, men have higher tuberculosis (TB) burden but the mechanisms underlying this sex disparity are not fully understood. Recent surveys of social mixing patterns have established moderate preferential within-sex mixing in many settings. This assortative mixing could amplify differences from other causes. We explored the impact of assortative mixing and factors differentially affecting disease progression and detection using a sex-stratified deterministic TB transmission model. We explored the influence of assortativity at disease-free and endemic equilibria, finding stronger effects during invasion and on increasing male:female prevalence (M:F) ratios than overall prevalence. Variance-based sensitivity analysis of endemic equilibria identified differential progression as the most important driver of M:F ratio uncertainty. We fitted our model to prevalence and notification data in exemplar settings within a fully Bayesian framework. For our high M:F setting, random mixing reduced equilibrium M:F ratios by 12% (95% CrI 0–30%). Equalizing male case detection there led to a 20% (95% CrI 11–31%) reduction in M:F ratio over 10 years—insufficient to eliminate sex disparities. However, this potentially achievable improvement was associated with a meaningful 8% (95% CrI 4–14%) reduction in total TB prevalence over this time frame.
Sequence-based GWAS and post-GWAS analyses reveal a key role of SLC37A1, ANKH, and regulatory regions on bovine milk mineral content
Authors: Sanchez Marie-Pierre , Rocha Dominique , Charles Mathieu , Boussaha Mekki , Hozé Chris , Brochard Mickaël , Delacroix-Buchet Agnès , Grosperrin Philippe , Boichard Didier
Published: April 2021

The mineral composition of bovine milk plays an important role in determining its nutritional and cheese-making value. Concentrations of the main minerals predicted from mid-infrared spectra produced during milk recording, combined with cow genotypes, provide a unique opportunity to decipher the genetic determinism of these traits. The present study included 1 million test-day predictions of Ca, Mg, P, K, Na, and citrate content from 126,876 Montbéliarde cows, of which 19,586 had genotype data available. All investigated traits were highly heritable (0.50–0.58), with the exception of Na (0.32). A sequence-based genome-wide association study (GWAS) detected 50 QTL (18 affecting two to five traits) and positional candidate genes and variants, mostly located in non-coding sequences. In silico post-GWAS analyses highlighted 877 variants that could be regulatory SNPs altering transcription factor (TF) binding sites or located in non-coding RNA (mainly lncRNA). Furthermore, we found 47 positional candidate genes and 45 TFs highly expressed in mammary gland compared to 90 other bovine tissues. Among the mammary-specific genes, SLC37A1 and ANKH, encoding proteins involved in ion transport were located in the most significant QTL. This study therefore highlights a comprehensive set of functional candidate genes and variants that affect milk mineral content.
Solubility of Ketoconazole (antifungal drug) in SC-CO2 for binary and ternary systems: measurements and empirical correlations
Authors: Sodeifian Gholamhossein , Sajadian Seyed Ali , Razmimanesh Fariba , Hazaveie Seyed Mojtaba
Published: April 2021

One of the main steps in choosing the drug nanoparticle production processes by supercritical carbon dioxide (SC-CO2) is determining the solubility of the solid solute. For this purpose, the solubility of Ketoconazole (KTZ) in the SC-CO2, binary system, as well as in the SC-CO2-menthol (cosolvent), ternary system, was measured at 308–338 K and 12–30 MPa using the static analysis method. The KTZ solubility in the SC-CO2 ranged between 0.20 × 10–6 and 8.02 × 10–5, while drug solubility in the SC-CO2 with cosolvent varied from 1.2 × 10–5 to 1.96 × 10–4. This difference indicated the significant effect of menthol cosolvent on KTZ solubility in the SC-CO2. Moreover, KTZ solubilities in the two systems were correlated by several empirical and semiempirical models. Among them, Sodeifian et al., Bian et al., MST, and Bartle et al. models can more accurately correlate experimental data for the binary system than other used models. Also, the Sodeifian and Sajadian model well fitted the solubility data of the ternary system with AARD% = 6.45, Radj = 0.995.
Ideas from the World of Information Science: A Model-driven Development
Authors: Papajorgji Petraq , Todri Ardita , Ilollari Orkida
Published: April 2021

This chapter presents the model-driven development approach in presenting the structure of the Mind Genomics software used to create studies in different areas of knowledge. At the center of the approach stands the model, presented by a class diagram, designed using the Unified Modeling Language (UML). The model shows the concepts contained in the model, their attributes and behaviour and the relationships among them to create the model. The model has many purposes such as showing the interrelationships among the concepts, the dependency among elements and the maintenace order. The model could be used to automatically generate the code for classes and the relations among classes.
Imputing Emotions to Foods
Authors: Harizi Ariola
Published: April 2021

This chapter deals with the effects of sensory marketing on buying food products, and introduces a new paradigm of ‘imputed emotions’ to the experiences involved in the purchase process, i.e., ‘buying’. Emerging application of human sensory science, namely sensory marketing, as a technique by which knowledge of sensory impressions, i.e., knowledge of sensory experiences, can help sell products and services is presented. Research suggest that shoppers are continually feeling a range of different emotions when they connect with brands. Feelings may be the most effective way to make sure that customers feel positive. The strategy of sensory marketing may be one of the smartest ways for any company to trigger emotion instantly in their audience, and maintain long-term engagement.
Consumer Testing with Children – Challenges and Opportunities
Authors: Donadini Gianluca , Spigno Giorgia
Published: April 2021

This chapter addresses some issues in consumer research with children and covers the current state of knowledge of chemosensory perceptions and preferences of children, extending its coverage to sensory and consumer-testing methodology applied to children. It also explains why careful consideration is required to the conduct of research in light of children's incomplete cognitive development and limited verbal and motor skills.
Molecular redox species for next-generation batteries
Authors: Cameron Jamie M. , Holc Conrad , Kibler Alexander J. , Peake Catherine L. , Walsh Darren A. , Newton Graham N. , Johnson Lee R.
Published: April 2021

In this Tutorial Review, we describe the critical role redox active molecular species are playing in the development of the next generation of “beyond-lithium ion” battery technologies.
A fast and ultrasensitive ELISA based on rolling circle amplification
Authors: You Minli , Peng Ping , Xue Zhenrui , Tong Haoyang , He Wanghong , Mao Ping , Liu Qi , Yao Chunyan , Xu Feng
Published: April 2021

The rolling circle amplification-based ELISA shows a 10 minutes fast amplification and 50 times improvement of sensitivity.
Chemo- and regioselective ring-opening of donor–acceptor oxiranes with N-heteroaromatics
Authors: Sang Ji-Wei , Xie Ming-Sheng , Wang Man-Man , Qu Gui-Rong , Guo Hai-Ming
Published: April 2021

The first ring-opening of D–A oxiranes with N-heteroaromatics in a chemoselective C–C bond cleavage manner was achieved, providing acyclic nucleoside analogues containing a N-glycosidic bond. The Ganciclovir analogue could be obtained by reduction.
A general concept for highly efficient covalent laser patterning of graphene based on silver carboxylates
Authors: Wei Tao , Liu Xin , Al-Fogra Sabrin , Bachmann Julien , Hauke Frank , Hirsch Andreas
Published: April 2021

Spatially resolved graphene architectures GA, GB, and GC containing different functional groups were efficiently constructed by a novel developed laser-writing concept.
Do equilibrium and rate constants of intramicellar reactions depend on micelle size?
Authors: Kohlmann Tim , Goez Martin
Published: April 2021

The duck test … on sodium alkyl sulfate micelles SnS: nanodroplets with the polarity of methanol and the viscosity of octanol, regardless of (precomputable) size.
A cobalt-based metal–organic framework and its derived material as sulfur hosts for aluminum–sulfur batteries with the chemical anchoring effect
Authors: Xiao Xiang , Tu Jiguo , Huang Zheng , Jiao Shuqiang
Published: April 2021

A novel high-performance aluminum–sulfur battery system using MOFs and MOF-derived polyhedrons as sulfur host materials with superior chemical anchoring effect.
Insight into bicarbonate involved efficient heterogeneous Fenton-like degradation of sulfamethoxazole over a CuFeO2 based composite under alkaline conditions
Authors: Dai Chu , Tian Xike , Feng Shuxuan , Nie Yulun , Li Yong , Lu Liqiang
Published: April 2021

Both radical and nonradical mechanisms were attributed to the enhanced SMX degradation under alkaline conditions in the presence of bicarbonate.
Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety
Authors: Meşeli Tuğba , Doğan Şengül Dilem , Gündüz Miyase Gözde , Kökbudak Zülbiye , Skaro Bogojevic Sanja , Noonan Theresa , Vojnovic Sandra , Wolber Gerhard , Nikodinovic-Runic Jasmina
Published: April 2021

Molecular modifications on sulfathiazole to overcome sulfonamide resistance: the discovery of selective antibacterial agents against Staphylococcus aureus.
A new 2D lanthanum based microporous MOF for efficient synthesis of cyclic carbonates through CO2 fixation
Authors: Kanti Das Sabuj , Ghosh Anirban , Bhattacharjee Sudip , Chowdhury Avik , Mitra Partha , Bhaumik Asim
Published: April 2021

We report a new microporous La-MOF La-5-SIP-MOF through solvothermal reaction and it showed high catalytic activity for the synthesis of cyclic carbonates from epoxides via the CO2 fixation reaction at room temperature.
Fabrication of an AAO-based surface-enhanced Raman scattering substrate for the identification of levofloxacin in milk
Authors: Li Nan , Han Siqingaowa , Lin Shuang , Sha Xuan-yu , Hasi Wuliji
Published: April 2021

On-site measurement of levofloxacin in milk via surface-enhanced Raman spectroscopy using a AAO-based SERS substrate.
Photocatalytic nitrogen fixation of metal–organic frameworks (MOFs) excited by ultraviolet light: insights into the nitrogen fixation mechanism of missing metal cluster or linker defects
Authors: Gao Wanguo , Li Xiaoman , Zhang Xu , Su Senda , Luo Shijian , Huang Rong , Jing Yuan , Luo Min
Published: April 2021

The photo-activated linker defect greatly improves the performance of photocatalytic nitrogen fixation, but not the cluster defect.
A convenient access to fluorophosphonium triflate salts by electrophilic fluorination and anion exchange
Authors: Guo Chun-Xiang , Yogendra Sivathmeehan , Gomila Rosa M. , Frontera Antonio , Hennersdorf Felix , Steup Johannes , Schwedtmann Kai , Weigand Jan J.
Published: April 2021

The in situ one-pot electrophilic fluorination of phosphanes with NFSI followed by anion exchange with MeOTf gives highly electrophilic fluorophosphonium triflates – highly efficient catalysts for the synthesis of N-sulfonylamidines from amides.
Abiological catalysis by myoglobin mutant with a genetically incorporated unnatural amino acid
Authors: Chand Subhash , Ray Sriparna , Yadav Poonam , Samanta Susruta , Pierce Brad S. , Perera Roshan
Published: April 2021

To inculcate biocatalytic activity in the oxygen-storage protein myoglobin (Mb), a genetically engineered myoglobin mutant H64DOPA (DOPA = L-3,4-dihydroxyphenylalanine) has been created. Incorporation of unnatural amino acids has already demonstrated their ability to accomplish many non-natural functions in proteins efficiently. Herein, the presence of redox-active DOPA residue in the active site of mutant Mb presumably stabilizes the compound I in the catalytic oxidation process by participating in an additional hydrogen bonding (H-bonding) as compared to the WT Mb. Specifically, a general acid-base catalytic pathway was achieved due to the availability of the hydroxyl moieties of DOPA. The reduction potential values of WT (E° = −260 mV) and mutant Mb (E° = −300 mV), w.r.t. Ag/AgCl reference electrode, in the presence of hydrogen peroxide, indicated an additional H-bonding in the mutant protein, which is responsible for the peroxidase activity of the mutant Mb. We observed that in the presence of 5 mM H2O2, H64DOPA Mb oxidizes thioanisole and benzaldehyde with a 10 and 54 folds higher rate, respectively, as opposed to WT Mb. Based on spectroscopic, kinetic, and electrochemical studies, we deduce that DOPA residue, when present within the distal pocket of mutant Mb, alone serves the role of His/Arg-pair of peroxidases.
A Nationwide Study Examining Deafness Among Hospitalized Adults
Authors: Harris Ché Matthew , Kotwal Susrutha , Wright Scott Mitchell
Published: April 2021

Background

It is unknown whether hospital outcomes differ among nonspeaking deaf patients compared to those without this disability.

Objective

This article aims to compare clinical outcomes and utilization data among patients with and without deafness.

Design

This study used a retrospective cohort study.

Setting and Participants

The participants included Nationwide Inpatient Sample, year 2017, hospitalized adults with and without diagnostic codes related to deafness and inability to speak.

Method

Multiple logistic and linear regression were used to compare in-hospital outcomes.

Results

Thirty million four hundred one thousand one hundred seventeen adults were hospitalized, and 7,180 had deafness and inability to speak related coding. Patients with deafness were older (mean age ±
SEM
: 59.2 ± 0.51 vs. 57.9 ± 0.09 years,
p
= .01), and less likely female (47.0% vs. 57.7%,
p
< .01) compared to controls. Those with deafness had more comorbidities compared to the controls (Charlson comorbidity score ≥ 3: 31.2% vs. 27.8%,
p
< .01). Mortality was higher among deaf versus controls (3.6% vs. 2.2%;
p
< .01); this translated into higher adjusted odds of mortality (adjusted odds ratio = 1.7. [confidence interval (CI) 1.3–2.4];
p
= .01). Deaf patients had lower odds of being discharged home compared to controls {aOR} = 0.6, (CI) 0.55–0.73];
p
< .01. Length of stay was longer (adjusted mean difference = 1.5 days CI [0.7–2.3];
p
< .01) and hospital charges were higher, but not significantly so (adjusted mean difference = $4,193 CI [−$1,935–$10,322];
p
= .18) in patients with deafness.

Conclusions

Hospitalized nonspeaking deaf patients had higher mortality and longer hospital stays compared to those without this condition. These results suggest that specialized attention may be warranted when deaf patients are admitted to our hospitals in hopes of reducing disparities in outcomes.

Supplemental Material

https://doi.org/10.23641/asha.14336663
Dysphagia Phenotypes in Spinal Muscular Atrophy: The Past, Present, and Promise for the Future
Authors: McGrattan Katlyn Elizabeth , Graham Robert J. , DiDonato Christine J. , Darras Basil T.
Published: April 2021

Purpose

The aim of this study was to provide clinicians with an overview of literature relating to dysphagia in spinal muscular atrophy (SMA) to guide assessment and treatment.

Method

In this clinical focus article, we review literature published in Scopus and PubMed between 1990 and 2020 pertaining to dysphagia in SMA across the life span. Original research articles that were published in English were included. Searches were conducted within four themes of inquiry: (a) etiology and phenotypes, (b) respiratory systemic deficits and management, (c) characteristics of natural history dysphagia and its treatment, and (d) dysphagia outcomes with disease-modifying therapies. Articles for the first two themes were selected by content experts who identified the most salient articles that would provide clinicians foundational background knowledge about SMA. Articles for the third theme were identified using search terms, includingspinal muscular atrophy,swallow,dysphagia,bulbar, nutrition,g-tube,alternative nutrition,jaw,mouth,palate,ORmandible. Search terms for the fourth theme includedspinal muscular atrophyANDnusinersenORAVXS-101/onasemnogene abeparvovec-xioi.

Review of Pertinent Literature

Twenty-nine articles were identified. Findings across identified articles support the fact that patients with SMA who do not receive disease-modifying therapy exhibit clinically significant deficits in oropharyngeal swallow function. Few investigations provided systematic information regarding the underlying physiological deficits responsible for this loss in function, the timing of the degradation, or how disease-modifying therapies change these outcomes.

Conclusion

Future research outlining the physiological and functional oropharyngeal swallowing deficits among patients with SMA who receive disease-modifying therapy is critical in developing standards of dysphagia care to guide clinicians.
Changes in Heart Rate Variability Following Acoustic Therapy in Individuals With Tinnitus
Authors: Reinhart Paul , Griffin Kendra , Micheyl Christophe
Published: April 2021

Purpose

The aim of the study was to investigate changes in autonomic function, as measured by heart rate variability, in individuals with tinnitus following acoustic therapy implemented using tinnitus maskers presented via hearing aids.

Method

Twenty-six individuals with tinnitus and hearing impairment completed an 8-week field trial wearing hearing aids providing acoustic therapy via three tinnitus masker options set just below minimum masking level. Tinnitus handicap was measured using the Tinnitus Handicap Inventory at baseline (before starting acoustic therapy) and posttreatment (at end of 8-week trial). Resting heart rate and heart rate variability were measured using electrocardiography at baseline and posttreatment.

Results

There was a significant decrease in tinnitus handicap posttreatment compared to baseline. There was no change in heart rate, but there was a significant increase in heart rate variability posttreatment compared to baseline.

Conclusions

Acoustic therapy using tinnitus maskers delivered via hearing aids provided tinnitus relief and produced a concurrent increase in heart rate variability, suggesting a decrease in stress. Heart rate variability is a potential biomarker for tracking efficacy of acoustic therapy; however, further research is required.
A novel face recognition method based on fusion of LBP and HOG
Authors: Chen Ting , Gao Tao , Li Shuying , Zhang Xi , Cao Jinpei , Yao Dachun , Li Yh
Published: April 2021

As one of the hot topics in the field of computer vision research, face recognition technology has received significant attention due to its potentiality for a wide range of applications in government as well as commercial purposes. In practical applications, although several existing face recognition methods have achieved good performances in specific scenes, they easily suffer from a sharp decline in recognition rate if affected by different conditions of light, expression, posture and occlusion. Among many factors, influences of complex illuminations on face recognition are particularly significant. To further improve the performance of the existing local binary pattern (LBP) operator, neighbourhood weighted average LBP (NWALBP) is first proposed for fully considering the strong correlations between pixel pairs in the neighbourhood, which extends the traditional LBP uni‐layer neighbourhood template window to the bi‐layer neighbourhood template window and calculates the weighted average of bi‐layer neighbourhood pixels in each direction. Then, inspired by center symmetric LBP (CS‐LBP), centre symmetric NWALBP (CS‐NWALBP) is further proposed, which can effectively reduce computation complexity by only comparing the weighted average values of the neighbourhood pixels that are symmetric about the centre pixel. Finally, by combining the merit of histogram of oriented gradient (HOG), a feature fusion algorithm named CS‐NWALBP+HOG is suggested. Several experiments have eventually demonstrated that our proposed algorithms have more robust performance under complex illumination conditions if compared with many other latest algorithms.
Design criteria of solid‐state circuit breaker for low‐voltage microgrids
Authors: Purgat Pavel , Shah Samad , van der Blij Nils , Qin Zian , Bauer Pavol
Published: April 2021

Solid‐state circuit breakers (SSCB) show great promise to become the key element in the protection of low‐voltage direct current microgrids. SSCBs operate in the microsecond range and employ semi‐conductor devices that have strict safe operation area limits. Therefore, the design of the SSCB needs to consider the effects of fault detection delays and semi‐conductor safe operation area limitations. This paper derives SSCB design criteria that consider the effect of different detection methods with different detection delays under varying system constraints. The design space is investigated in a sensitivity analysis, which provides insights into the operation boundaries of SSCB and explains how a combination of fault detection methods can reduce the SSCB size. The insights from the theoretical and sensitivity analysis are used to propose an SSCB design flowchart. SSCB prototype is developed and tested in different scenarios under nominal grid voltage and current. The derived design constraints can be used for efficient SSCB design and also to evaluate the effects of different protection schemes on the required SSCB size.
ERRATUM: Cylindrical optimal rearrangement problem leading to a new type obstacle problem
Authors: Mikayelyan Hayk
Published: April 2021

A mistake in the proof of the Theorem 5.5 on page 870 in [H. Mikayelyan, ESAIM: COCV 24 (2018) 859–872] has been found.