bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Compensatory Insulin Receptor (IR) Activation on Inhibition of Insulin-Like Growth Factor-1 Receptor (IGF-1R): Rationale for Cotargeting IGF-1R and IR in Cancer
Authors: Buck Elizabeth , Gokhale Prafulla C. , Koujak Susan , Brown Eric , Eyzaguirre Alexandra , Tao Nianjun , Rosenfeld-Franklin Maryland , Lerner Lorena , Chiu M. Isabel , Wild Robert , Epstein David , Pachter Jonathan A. , Miglarese Mark R.
Published: April 2023

Abstract
Insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase (RTK) and critical activator of the phosphatidylinositol 3-kinase–AKT pathway. IGF-1R is required for oncogenic transformation and tumorigenesis. These observations have spurred anticancer drug discovery and development efforts for both biological and small-molecule IGF-1R inhibitors. The ability for one RTK to compensate for another to maintain tumor cell viability is emerging as a common resistance mechanism to antitumor agents targeting individual RTKs. As IGF-1R is structurally and functionally related to the insulin receptor (IR), we asked whether IR is tumorigenic and whether IR-AKT signaling contributes to resistance to IGF-1R inhibition. Both IGF-1R and IR(A) are tumorigenic in a mouse mammary tumor model. In human tumor cells coexpressing IGF-1R and IR, bidirectional cross talk was observed following either knockdown of IR expression or treatment with a selective anti–IGF-1R antibody, MAB391. MAB391 treatment resulted in a compensatory increase in phospho-IR, which was associated with resistance to inhibition of IRS1 and AKT. In contrast, treatment with OSI-906, a small-molecule dual inhibitor of IGF-1R/IR, resulted in enhanced reduction in phospho-IRS1/phospho-AKT relative to MAB391. Insulin or IGF-2 activated the IR-AKT pathway and decreased sensitivity to MAB391 but not to OSI-906. In tumor cells with an autocrine IGF-2 loop, both OSI-906 and an anti–IGF-2 antibody reduced phospho-IR/phospho-AKT, whereas MAB391 was ineffective. Finally, OSI-906 showed superior efficacy compared with MAB391 in human tumor xenograft models in which both IGF-1R and IR were phosphorylated. Collectively, these data indicate that cotargeting IGF-1R and IR may provide superior antitumor efficacy compared with targeting IGF-1R alone. Mol Cancer Ther; 9(10); 2652–64. ©2010 AACR.
Data from A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis
Authors: Huesca Mario , Lock Lisa S. , Khine Aye Aye , Viau Stéphane , Peralta Robert , Cukier I. Howard , Jin Hongnan , Al-Qawasmeh Raed A. , Lee Yoon , Wright Jim , Young Aiping
Published: April 2023

Abstract
ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G1-S phase arrest of cell proliferation. The antiproliferative and antitumor activity of ML-133 described in the present study suggests modulation of intracellular zinc homeostasis as a potential strategy for the treatment of several cancer types, and ML-133 represents a promising new class of antitumor agents that deserves further development. [Mol Cancer Ther 2009;8(9):2586–96]
Data from Dual Inhibition of Akt/Mammalian Target of Rapamycin Pathway by Nanoparticle Albumin-Bound–Rapamycin and Perifosine Induces Antitumor Activity in Multiple Myeloma
Authors: Cirstea Diana , Hideshima Teru , Rodig Scott , Santo Loredana , Pozzi Samantha , Vallet Sonia , Ikeda Hiroshi , Perrone Giulia , Gorgun Gullu , Patel Kishan , Desai Neil , Sportelli Peter , Kapoor Shweta , Vali Shireen , Mukherjee Siddhartha , Munshi Nikhil C. , Anderson Kenneth C. , Raje Noopur
Published: April 2023

Abstract
The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple myeloma (MM) cell proliferation, survival, and development of drug resistance, underscoring the role of mTOR inhibitors, such as rapamycin, with potential anti-MM activity. However, recent data show a positive feedback loop from mTOR/S6K1 to Akt, whereby Akt activation confers resistance to mTOR inhibitors. We confirmed that suppression of mTOR signaling in MM cells by rapamycin was associated with upregulation of Akt phosphorylation. We hypothesized that inhibiting this positive feedback by a potent Akt inhibitor perifosine would augment rapamycin-induced cytotoxicity in MM cells. Perifosine inhibited rapamycin-induced phosphorylated Akt, resulting in enhanced cytotoxicity in MM.1S cells even in the presence of interleukin-6, insulin-like growth factor-I, or bone marrow stromal cells. Moreover, rapamycin-induced autophagy in MM.1S MM cells, as evidenced by electron microscopy and immunocytochemistry, was augmented by perifosine. Combination therapy increased apoptosis detected by Annexin V/propidium iodide analysis and caspase/poly(ADP-ribose) polymerase cleavage. Importantly, in vivo antitumor activity and prolongation of survival in a MM mouse xenograft model after treatment was enhanced with combination of nanoparticle albumin-bound–rapamycin and perifosine. Utilizing the in silico predictive analysis, we confirmed our experimental findings of this drug combination on PI3K, Akt, mTOR kinases, and the caspases. Our data suggest that mutual suppression of the PI3K/Akt/mTOR pathway by rapamycin and perifosine combination induces synergistic MM cell cytotoxicity, providing the rationale for clinical trials in patients with relapsed/refractory MM. Mol Cancer Ther; 9(4); 963–75. ©2010 AACR.
Data from Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans
Authors: Huang R. Stephanie , Duan Shiwei , Kistner Emily O. , Hartford Christine M. , Dolan M. Eileen
Published: April 2023

Abstract
To gain a better understanding of the genetic variants associated with carboplatin-induced cytotoxicity in individuals of African descent, we present a step-wise approach integrating genotypes, gene expression, and sensitivity of HapMap cell lines to carboplatin. Cell lines derived from 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to carboplatin-induced cytotoxicity. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of carboplatin for 72 h. Gene expression of 89 HapMap YRI cell lines was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. Single nucleotide polymorphism genotype and the percent survival at different treatment concentrations along with carboplatin IC50 were linked through whole genome association. A second association test was done between single nucleotide polymorphism genotype and gene expression, and linear regression was then used to capture those genes whose expression correlated to drug sensitivity phenotypes. This approach allows us to identify genetic variants that significantly associate with sensitivity to the cytotoxic effects of carboplatin through their effect on gene expression. We found a gene (GPC5) whose expression is important in all carboplatin treatment concentrations as well as many genes unique to either low (e.g., MAPK1) or high (e.g., BRAF, MYC, and BCL2L1) concentrations of drug. Our whole genome approach enables us to evaluate the contribution of genetic and gene expression variation to a wide range of cellular phenotypes. The identification of concentration specific genetic signatures allows for potential integration of pharmacokinetics, pharmacodynamics, and pharmacogenetics in tailoring chemotherapy. [Mol Cancer Ther 2008;7(9):3038–46]
Data from Antibodies targeting hepatoma-derived growth factor as a novel strategy in treating lung cancer
Authors: Ren Hening , Chu Zuoming , Mao Li
Published: April 2023

Abstract
Hepatoma-derived growth factor (HDGF) is overexpressed in lung cancer and the overexpression correlates with aggressive biological behaviors and poor clinical outcomes. We developed anti-HDGF monoclonal antibodies and tested their antitumor activity in lung cancer xenograft models. We also determined biological effects in tumors treated with the antibody alone or in combination with bevacizumab/avastin (an anti-vascular endothelial growth factor antibody) and/or gemcitabine (a chemotherapeutic agent). We found the anti-HDGF was effective to inhibit tumor growth in non-small cell lung cancer xenograft models. In the A549 model, compared with control IgG, tumor growth was substantially inhibited in animals treated with anti-HDGF antibodies, particularly HDGF-C1 (P = 0.002) and HDGF-H3 (P = 0.005). When HDGF-H3 was combined with either bevacizumab or gemcitabine, we observed enhanced tumor growth inhibition, particularly when the three agents were used together. HDGF-H3-treated tumors exhibited significant reduction of microvessel density with a pattern distinctive from the microvessel reduction pattern observed in bevacizumab-treated tumors. HDGF-H3-treated but not bevacizumab-treated tumors also showed a significant increase of apoptosis. Interestingly, many of the apoptotic cells in HDGF-H3-treated tumors are stroma cells, suggesting that the mechanism of the antitumor activity is, at least in part, through disrupting formation of tumor-stroma structures. Our results show that HDGF is a novel therapeutic target for lung cancer and can be effectively targeted by an antibody-based approach.[Mol Cancer Ther 2009;8(5):1106–12]
Data from Orphan G protein–coupled receptor GPR56 plays a role in cell transformation and tumorigenesis involving the cell adhesion pathway
Authors: Ke Ning , Sundaram Roshni , Liu Guohong , Chionis John , Fan Wufang , Rogers Cheryl , Awad Tarif , Grifman Mirta , Yu Dehua , Wong-Staal Flossie , Li Qi-Xiang
Published: April 2023

Abstract
GPR56 is an orphan G protein–coupled receptor, mutations of which have recently been associated with bilateral frontoparietal polymicrogyria, a rare neurologic disease that has implications in brain development. However, no phenotype beyond central nervous system has yet been described for the GPR56-null mutations despite abundant GPR56 expression in many non–central nervous system adult tissues. In the present study, we show that higher GPR56 expression is correlated with the cellular transformation phenotypes of several cancer tissues compared with their normal counterparts, implying a potential oncogenic function. RNA interference–mediated GPR56 silencing results in apoptosis induction and reduced anchorage-independent growth of cancer cells via increased anoikis, whereas cDNA overexpression resulted in increased foci formation in mouse fibroblast NIH3T3 cell line. When GPR56 silencing was induced in vivo in several xenograft tumor models, significant tumor responses (including regression) were observed, suggesting the potential of targeting GPR56 in the development of tumor therapies. The expression profiling of GPR56-silenced A2058 melanoma cell line revealed several genes whose expression was affected by GPR56 silencing, particularly those in the integrin-mediated signaling and cell adhesion pathways. The potential role of GPR56 in cancer cell adhesion was further confirmed by the observation that GPR56 silencing also reduced cell adhesion to the extracellular matrix, which is consistent with the observed increase in anoikis and reduction in anchorage-independent growth phenotypes. The oncogenic potential and apparent absence of physiologic defects in adult human tissues lacking GPR56, as well as the targetable nature of G protein–coupled receptor by small molecule or antibody, make GPR56 an attractive drug target for the development of cancer therapies. [Mol Cancer Ther 2007;6(6):1840–50]
Data from Suppression of cervical carcinoma cell growth by intracytoplasmic codelivery of anti-oncoprotein E6 antibody and small interfering RNA
Authors: Courtête Jérôme , Sibler Annie-Paule , Zeder-Lutz Gabrielle , Dalkara Deniz , Oulad-Abdelghani Mustapha , Zuber Guy , Weiss Etienne
Published: April 2023

Abstract
Cervical cancer is caused by high-risk types of human papillomaviruses (HPV) that encode the E6 and E7 oncogenes. Silencing of E6 gene expression in HPV-positive cell lines by transfection of small interfering RNA (siRNA) with cationic lipids restores the dormant p53 tumor suppressor pathway. Because cationic lipids can also be used for intracytoplasmic delivery of proteins, we tested whether the delivery of monoclonal antibodies that bind to HPV16 E6 and neutralize its biological activity in vitro could restore p53 function in tumor cells. Here, we show that the 4C6 antibody is efficiently delivered into the cell cytoplasm using a lipidic reagent used for siRNA transfection. The delivery of 4C6 resulted in the nuclear accumulation of p53 protein in CaSki and SiHa cells but not in HeLa cells. Furthermore, the antibody-mediated p53 response was dramatically increased when a peptide corresponding to the 4C6 epitope and bearing a COOH-terminal cysteine residue was added to the transduction mixture. We found that a fraction of the added peptides were dimers that allowed the formation of antibody polymers adsorbed onto the lipidic matrix. With this system, the proliferation of CaSki and SiHa cells was strongly diminished, but no apoptosis was detectable. Remarkably, cell growth was almost totally suppressed by the addition of E6-specific siRNA to the transduction complex. The results indicate that the activity of E6 oncoprotein can be down-regulated in vivo by lipid-mediated antibody delivery and that antibodies and siRNA act synergistically when codelivered. This novel targeting strategy is simple to implement and may find therapeutic applications. [Mol Cancer Ther 2007;16(5):1728–35]
Data from A two-tiered physiologically based model for dually labeled single-chain Fv-Fc antibody fragments
Authors: Ferl Gregory Z. , Kenanova Vania , Wu Anna M. , DiStefano Joseph J.
Published: April 2023

Abstract
Monoclonal antibodies (mAb) are being used at an increasing rate in the treatment of cancer, with current efforts focused on developing engineered antibodies that exhibit optimal biodistribution profiles for imaging and/or radioimmunotherapy. We recently developed the single-chain Fv-Fc (scFv-Fc) mAb, which consists of a single-chain antibody Fv fragment (light-chain and heavy-chain variable domains) coupled to the IgG1 Fc region. Point mutations that attenuate binding affinity to FcRn were introduced into the Fc region of the wild-type scFv-Fc mAb, resulting in several new antibodies, each with a different half-life. Here, we describe the construction of a two-tiered physiologically based pharmacokinetic model capable of simulating the apparent biodistribution of both 111In- and 125I-labeled scFv-Fc mAbs, where 111In-labeled metabolites from degraded 111In-labeled mAbs tend to become trapped within the lysosomal compartment, whereas free 125I from degraded 125I-labeled mAbs is quickly eliminated via the urinary pathway. The different concentration-time profiles of 111In- and 125I-labeled mAbs permits estimation of the degradation capacity of each organ and elucidates the dependence of cumulative degradation in liver, muscle, and skin on FcRn affinity and tumor mass. Liver is estimated to account for ∼50% of all degraded mAb when tumor is small (∼0.1 g) and drops to about 35% when tumor mass is larger (∼0.3 g). mAb degradation in residual carcass (primarily skin and muscle) decreases from ∼45% to 16% as FcRn affinity of the three mAb variants under consideration increases. In addition, elimination of a small amount of mAb in the kidneys is shown to be required for a successful fit of model to data. [Mol Cancer Ther 2006;5(6):1550–8]
Synthetic biology, genetic circuits and machine learning: a new age of cancer therapy
Authors: Prasad Krishneel , Cross Ryan S. , Jenkins Misty R.
Published: April 2023

Synthetic biology has made it possible to rewire natural cellular responses to treat disease, notably demonstrated by chimeric antigen receptor (CAR) T cells as cancer immunotherapy. Building on the success of T‐cell activation using synthetic receptors, the field is now investigating how induction of noncanonical signalling pathways and sophisticated synthetic gene circuitry can enhance the antitumour phenotype of engineered T cells. This commentary explores two recently published studies that provide proof of concept for how new technologies achieve this. The first demonstrated that non‐naturally occurring combinations of signalling motifs derived from various immune receptors and arranged as a CAR drove unique signal transduction pathways in T cells and improved their tumour killing ability. Here, machine learning complemented the screening process and successfully predicted CAR T‐cell phenotype dependent on signalling motif choice. The second explored how synthetic zinc fingers can be engineered into controllable transcriptional regulators, where their activity was dependent on the presence or absence of FDA‐approved small‐molecule drugs. These studies are pivotal in expanding the design choices available for gene circuits of the future and highlight how a single cellular therapy could respond to multiple environmental cues including target cell antigen expression, the tumour microenvironment composition and small molecule drugs.
Tyrosinase‐activated Nanocomposites for Double‐Modals Imaging Guided Photodynamic and Photothermal Synergistic Therapy
Authors: Li Shuo , Zhang Guoyang , Peng Yanghan , Chen Peiyu , Li Jiguang , Wang Xuefei , Wang Zhuo
Published: April 2023

Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr‐obes‐based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic‐photothermal activity by regulating the balance between radiative decay and non‐radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria‐targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR‐activated imaging and photodynamic‐photothermal therapy of melanoma. The development of TYR‐activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.
Fundamentals and Applications of Raman‐Based Techniques for the Design and Development of Active Biomedical Materials
Authors: Fernández‐Galiana Álvaro , Bibikova Olga , Vilms Pedersen Simon , Stevens Molly M.
Published: April 2023

Raman spectroscopy is an analytical method based on light–matter interactions that can interrogate the vibrational modes of matter and provide representative molecular fingerprints. Mediated by its label‐free, non‐invasive nature, and high molecular specificity, Raman‐based techniques have become ubiquitous tools for in situ characterization of materials. This review comprehensively describes the theoretical and practical background of Raman spectroscopy and its advanced variants. The numerous facets of material characterization that Raman scattering can reveal, including biomolecular identification, solid‐to‐solid phase transitions, and spatial mapping of biomolecular species in bioactive materials, are highlighted. The review illustrates the potential of these techniques in the context of active biomedical material design and development by highlighting representative studies from the literature. These studies cover the use of Raman spectroscopy for the characterization of both natural and synthetic biomaterials, including engineered tissue constructs, biopolymer systems, ceramics, and nanoparticle formulations, among others. To increase the accessibility and adoption of these techniques, the present review also provides the reader with practical recommendations on the integration of Raman techniques into the experimental laboratory toolbox. Finally, perspectives on how recent developments in plasmon‐ and coherently‐enhanced Raman spectroscopy can propel Raman from underutilized to critical for biomaterial development are provided.
Horizontal and Vertical Coalescent Microrobotic Collectives Using Ferrofluid Droplets
Authors: Sun Mengmeng , Yang Shihao , Jiang Jialin , Zhang Li
Published: April 2023

Many artificial miniature robotic collectives have been developed to overcome the inherent limitations of inadequate individual capabilities. However, the basic building blocks of the reported collectives are mainly in the solid state, where the morphological boundaries of internal individuals are clear and cannot genuinely merge. Miniature robotic collectives based on liquid units still need to be explored; such on‐demand mergeable swarm systems are advantageous for adapting to the changing external environment. Here, a strategy to achieve a coalescent collective system we presented that exploits the ferrofluid droplets' splitting and coalescence properties to trigger the formation of horizontal multimodal and vertical gravity‐resistant collectives and unveil pattern‐enabled robotic functionalities. When subjected to a time‐varying magnetic field, the droplet swarm exhibits a variety of morphologies ranging from horizontal collectives, including vortex‐like, chain‐like, and crystal‐like patterns to vertical layer‐upon‐layer patterns. Using experiments and simulations, the formation and transformation of different morphological collectives are shown and their robust environmental adaptability are demonstrated. Potential applications of the multimodal droplet collectives are presented, including exploring an unknown environment, targeted object delivery, and fluid flow filtration in a lab‐on‐a‐chip. This work may facilitate the design of microrobotic swarm systems and expand the range of materials for miniature robots.
Curated collections for educators: Nine key articles and article series for teaching qualitative research methods
Authors: Lin Sophia , Zimmerman Elise , Datta Suchismita , Selby Maurice , Chan Teresa , Fant Abra
Published: April 2023

Background

Qualitative research explains observations, focusing on how and why phenomena and experiences occur. Qualitative methods go beyond quantitative data and provide critical information inaccessible through quantitative methods. However, at all levels of medical education, there is insufficient exposure to qualitative research. As a result, residents and fellows complete training ill‐equipped to appraise and conduct qualitative studies. As a first step to increasing education in qualitative methods, we sought to create a curated collection of papers for faculty to use in teaching qualitative research at the graduate medical education (GME) level.

Methods

We conducted literature searches on the topic of teaching qualitative research to residents and fellows and queried virtual medical education and qualitative research communities for relevant articles. We searched the reference lists of all articles found through the literature searches and online queries for additional articles. We then conducted a three‐round modified Delphi process to select papers most relevant to faculty teaching qualitative research.

Results

We found no articles describing qualitative research curricula at the GME level. We identified 74 articles on the topic of qualitative research methods. The modified Delphi process identified the top nine articles or article series most relevant for faculty teaching qualitative research. Several articles explain qualitative methods in the context of medical education, clinical care, or emergency care research. Two articles describe standards of high‐quality qualitative studies, and one article discusses how to conduct the individual qualitative interview to collect data for a qualitative study.

Conclusions

While we identified no articles reporting already existing qualitative research curricula for residents and fellows, we were able to create a collection of papers on qualitative research relevant to faculty seeking to teach qualitative methods. These papers describe key qualitative research concepts important in instructing trainees as they appraise and begin to develop their own qualitative studies.
Ene Reductase Enabled Intramolecular β‐C−H Functionalization of Substituted Cyclohexanones for Efficient Synthesis of Bridged Bicyclic Nitrogen Scaffolds
Authors: Jiang Guangde , Huang Chunshuai , Harrison Wesley , Li Hongxiang , Zhou Megan , Zhao Huimin
Published: April 2023

Herein we report that ene reductases (EREDs) can facilitate an unprecedented intramolecular β‐C−H functionalization reaction for the synthesis of bridged bicyclic nitrogen heterocycles containing the 6‐azabicyclo[3.2.1]octane scaffold. To streamline the synthesis of these privileged motifs, we developed a gram‐scale one‐pot chemoenzymatic cascade by combining iridium photocatalysis with EREDs, using readily available N‐phenylglycines and cyclohexenones that can be obtained from biomass. Further derivatization using enzymatic or chemical methods can convert 6‐azabicyclo[3.2.1]octan‐3‐one into 6‐azabicyclo[3.2.1]octan‐3α‐ols, which can be potentially utilized for the synthesis of azaprophen and its analogues for drug discovery. Mechanistic studies revealed the reaction requires oxygen, presumably to produce oxidized flavin, which can selectively dehydrogenate the 3‐substituted cyclohexanone derivatives to form the α,β‐unsaturated ketone, which subsequently undergoes spontaneous intramolecular aza‐Michael addition under basic conditions.
Solution Plasma‐Assisted Multivariate Metal Nanoalloys Encapsulated with Carbon Dots for Efficient Oxygen Evolution Reaction
Authors: Yan Fufeng , Ding Junyi , Hu Lijun , Li Sizhuan , Zhang Shuai , Wang Minghua , He Linghao , Du Miao
Published: April 2023

To accelerate the reaction kinetics of electrocatalytic oxygen evolution reaction (OER), a multicomponent CDs@(PdFeNiCo)Nbx nanohybrid comprising multiple metal nanoalloys and carbon quantum dots (CDs) was in situ generated by treating the mixture of Nb2C quantum dots (Nb2C QDs) and a variety of metal ions (M2+=Pd2+, Fe2+, Co2+, Ni2+) through the solution plasma (SP) modification technique. The CDs@(PdFeNiCo)Nbx catalyst was further explored as an electrocatalyst for OER in alkaline solution. Under nitrogen plasma irradiation with high input power (200 W), diverse bimetallic nanoalloy particles, including NbPd3, FeNb, NbNi3, and CoNbO4 nanoalloys, were generated, accompanied with the decomposition of Nb2C QDs into CDs. In view of the synergic effect between multivariate metal active sites and highly conjugated CD network, the developed CDs@(PdFeNiCo)Nbx electrocatalyst showed a small overpotential of 240 mV for achieving the current density of 10 mA cm−2, together with a very low Tafel slope of 62 mV dec−1, which substantially outperformed those of the state‐of‐the‐art metal electrocatalysts and was competitive with most metal oxides. The CDs@(PdFeNiCo)Nbx electrocatalyst also showed a negligible overpotential change during 30 h chronopotentiometry measurement. The present work can provide a feasible alternative strategy for the development of an excellent OER electrocatalyst using the SP modification method.
Expression of α‐Synuclein in the mouse retina is confined to inhibitory presynaptic elements
Authors: Yang Qingwen , Lin Xin , Xiao Jiayi , Zhong Wenhui , Wang Fenglan , Tan Hang , Rao Bilin , Qu Jia , Zhang Jun
Published: April 2023

α‐Synuclein (α‐Syn) is enriched in presynaptic terminals of the central nervous system including the retina and plays a role in the synaptic vesicle cycle and synaptic transmission. Abnormal aggregation of α‐Syn is considered to be the main component of the Lewy bodies that are the pathological hallmarks of Parkinson's disease. Although expression pattern of α‐Syn has been described in the retinas, its precise cellular and subcellular locations are poorly understood. We investigated the precise expression of α‐Syn using light microscopy (LM) and electron microscopy (EM) with antibodies against α‐Syn in the mouse retina. We found that the majority of α‐Syn immunoreactivity (IR) is located in GABAergic, glycinergic, and dopaminergic amacrine cells, and their processes often make a direct synapse to other labeled or unlabeled amacrine profiles, bipolar cell terminals, or ganglion cell dendrites. Further, our LM and immuno‐EM results confirm the absence of α‐Syn in excitatory photoreceptors, bipolar cell bodies, and their ribbon synapses, providing evidence, for the first time, that ribbon synapses do not express α‐Syn. Additionally, α‐Syn IR is located in the ganglion cells, some of which are intrinsically photosensitive retinal ganglion cells. These results reveal a previously unappreciated inhibitory synapse‐specific expression pattern of α‐Syn in the retina, suggesting that α‐Syn may play a distinct role in the modulation and integration of inhibitory synaptic transmission in the retina.
Negative effects of urbanization on plants: A global meta‐analysis
Authors: Hou Yuchen , Li Junsheng , Li Guo , Qi Wei
Published: April 2023

Understanding the response of plant diversity to urbanization is essential for conserving urban biodiversity. In this paper, a meta‐analysis of 34 articles and 163 observations regarding the impact of urbanization on plant diversity was conducted. The results revealed that urbanization had marked negative effects on plants. Urbanization had positive effects on introduced species and negative effects on native species. In the subgroup analysis, we found that trees responded better to the effect of urbanization than herbs and shrubs. There was no evidence that urban size, population density, nighttime light, and GDP per capita had moderating effects on plant richness. Based on meta‐regression analyses, native species in urban areas were less affected by urbanization at lower latitudes. Overall, urbanization had a marginally negative effect on plant abundance. The effects of urbanization on plant diversity during different stages of urban development were inconsistent. Our research shows that the suburbs play a crucial role in the urbanization gradient; there, plants survive with high species richness.
Monitoring the courtship flight trajectory of Latham's snipe (Gallinago hardwickii) using microphone arrays
Authors: Matsubayashi Shiho , Osaka Hideki , Suzuki Reiji , Nakadai Kazuhiro , Okuno Hiroshi G.
Published: April 2023

This study is the first to quantitatively measure the courtship display flights of Latham's snipe (Gallinago hardwickii), which is a “near threatened” species as of 2022 (IUCN red list of threatened species). By using a 16‐channel microphone array and 8‐channel microphone arrays, we localized the fine‐scale movements of courtship flights of one male performing at high altitude and high speed, and we estimated the direction from which each sound arrived using robot audition. Preliminary analyses of the azimuthal and elevation angles of the courtship flights partially revealed a fine‐scale flight trajectory. First, a male Latham's snipe gradually gained altitude while vocalizing sharp and harsh repeating calls, until it reached the flight peak altitude, then dove down while producing winnowing sound to the ground along the wetland zones without tall vegetation. This observation method is methodologically useful to establish a better understanding of Latham's snipe courtship flight site selection. Furthermore, this method can be extended to investigate other rare nocturnal or crepuscular birds that are too timid to risk ringing or tagging.
Niches of three sympatric montane ground‐dwelling squirrels: Relative importance of climate, topography, and landcover
Authors: Rossi Aviva J. , Klinger Robert C. , Hellwig Elise C. , Van Vuren Dirk H.
Published: April 2023

Species with different ecological niches will likely exhibit distinct responses to a changing environment. Differences in the magnitude of niche specialization may also indicate which species may be more vulnerable to environmental change, as many life‐history characteristics are known to affect climate change vulnerability. We characterized the niche space of three sympatric high‐elevation ground‐dwelling squirrels, yellow‐bellied marmot (Marmota flaviventer), Belding's ground squirrel (Urocitellus beldingi), and golden‐mantled ground squirrel (Callospermophilus lateralis), in the alpine and upper subalpine regions of the Sierra Nevada in California. We used 5879 observations of individual squirrels, collected from 4 years (2009–2012) of transect survey data, to quantify which ecogeographical variable types (climate, topography, or landcover) were most important in defining the niche of each species. We conducted Ecological Niche Factor Analysis to quantify the niche and generate indices of “marginality” (magnitude of selection) and “specialization” (narrowness of niche space). All three species demonstrated differential use of niche space when compared to the available niche space. Moreover, the relative importance of the variables shaping the niche differed among these species. For example, the presence of meadows was important in defining the niche for U. beldingi and M. flaviventer, but the presence of conifers was important to C. lateralis. Precipitation was important in defining the niche for all three species, positively so for U. beldingi, and negatively for the other two species. The niche breadth of these three species was also positively associated with geographic range size. Mammals in high‐elevation mountain systems often are perceived as vulnerable to climate shifts, but our results underscore the importance of also including non‐climate‐based factors in defining the niche. The overall magnitude of niche selection for all three species was driven by a combination of topographic, climatic, and landcover factors; thus, efforts to forecast areas where these species can persist in the future need to evaluate from more than just a climatic perspective.
A COmplex PRoportional ASsessment and Gray Relational Analysis methodology hybrid optimization of compression ignition engine distinctiveness fuelled by dual feed stock pyrolysis of Annona squamosa seed particles and Aegle marmelos pressed seed cake pyrolytic liquid‐diesel opus
Authors: Raju Sasikumar , Paramasivam Baranitharan
Published: April 2023

The deficiency of fossil fuel resources, amplifying fuel price and its related environmental anxieties grasped great attention for finding an alternative fuel. Such alternative options can be fuels obtained from agricultural residues, plants, and wastes. The present research emphases on complex proportional assessment (COPRAS) and gray relational analysis (GRA) modeling of a diesel engine fuelled by Annona squamosa (AS) and Aegle marmelos (AM) co‐pyrolysis oil/diesel binary opus as an engine fuel to optimize the engine characteristics. Co‐pyrolysis oil is obtained from AS+AM feedstock at pyrolysis temperature of 500°C. To obtain engine data for training and testing the proposed COPRAS and GRA models were adopted for the engine control factors such as engine load (W) and compression ratio (CR) in a test engine rig through experimentation and hybrid optimization technics. From the engine output responses reveals that F2080 opus delivers an augmented brake thermal efficiency (22.01%) than diesel (21.56%) at peak load. Subsequently, F2080 fuel emits substantial lessening of CO (11.88%) and HC (5.64%) emissions as compared to diesel (F0). Based on the results, it is conclude that F2080 blend at CR of 17.5 and 100% load was delivered the greater engine distinctiveness through optimization outcomes and experimental evaluation compared to F0.
Tomato flu 2022 outbreak in India: Issues, challenges, and possible solutions
Authors: Adesola Ridwan Olamilekan , Idris Ibrahim , Opuni Emmanuel , D'Souza Joanna Nicole
Published: April 2023

Background and Aims

The outbreak of Tomato flu in India has affected the children making the parents tremble in worry and pain. The outbreak of this disease first occurred in India affecting young children below 5 years of age, thereby causing a threat to the country, neighboring countries, and the rest of the world—although no death is yet recorded. The aim of this research is to discuss the issues, challenges, and possible solutions associated with 2022 Tomato flu outbreaks in India.

Results

Tomato flu is caused by Coxsackievirus A16 as confirmed in the United Kingdom. The health authorities are currently monitoring the spread of the virus and trying to understand it to develop strategies to contain it. But they are left with some challenges relating to the health system, surveillance, and adherence to preventive protocols among others.

Conclusion

To prevent the spread of Tomato flu to other neighboring countries like China, Bangladesh, Pakistan, Sri Lanka, Myanmar, Afghanistan, Bhutan, Nepal, and the Maldives, the Indian Government must provide adequate public health control measures to contain the disease in children. Various recommendations have been given below.
Cytotoxic effects of psychoactive isobutyrylfentanyl and its halogenated derivatives on isolated rat hepatocytes
Authors: Nakagawa Yoshio , Suzuki Jin , Suzuki Toshinari , Takahashi Hideyo , Makino Kosho , Ono Yasushi , Sakamoto Miho , Inomata Akiko
Published: April 2023

The novel and numerous psychoactive compounds derived from the analgesic prescription drug N‐phenyl‐N‐[1‐(2‐phenylethyl)piperidin‐4‐yl]propanamide (fentanyl) have been illegally abused as recreational drugs and caused numerous fatalities. Because some psychoactive/psychotropic drugs are known to be hepatotoxic in humans and experimental animals, the cytotoxic effects and mechanisms of 4‐fluoroisobutyrylfentanyl (4F‐iBF), 4‐chloroisobutyrylfentanyl (4Cl‐iBF), and the parent compound isobutyrylfentanyl (iBF) were studied in freshly isolated rat hepatocytes. 4F‐iBF caused not only concentration (0–2.0 mM)‐ and time (0–3 h)‐dependent cell death accompanied by the depletion of cellular ATP and reduced glutathione (GSH) and protein thiol levels but also the accumulation of oxidized glutathione. Of these fentanyls examined, 4Cl‐iBF/4F‐iBF‐induced cytotoxicity with the loss of mitochondrial membrane potential at concentrations of 0.5 and 1.0 mM and the production of reactive oxygen species (ROS) at 0.5 mM were greater than those induced by iBF. The pretreatment of hepatocytes with N‐acetyl‐l‐cysteine as a precursor of cellular GSH ameliorated, at least in part, cytotoxicity accompanied by insufficient ATP levels, the loss of mitochondrial membrane potential, and generation of ROS caused by 4Cl‐iBF/4F‐iBF, whereas pretreatment with diethyl maleate as a GSH depletor enhanced fentanyl‐induced cytotoxicity accompanied by the rapid loss of cellular GSH. Taken collectively, these results indicate that the onset of cytotoxic effects caused by these fentanyls is partially attributable to cellular energy stress as well as oxidative stress.
“Inside” versus “outside” trends in consumer research
Authors: Camilleri Edwin , Garg Nitika , Miah Shah Jahan
Published: April 2023

Given its multi‐faceted nature, consumer research has evinced interest from scholars both within and outside the marketing domain, resulting in ongoing knowledge contributions from a diverse range of disciplines. We conduct a comprehensive review and comparison across both marketing (“inside”) and non‐marketing (“outside”) disciplines to identify which topics are most and least focused on within each disciplinary domain and which are emerging as the most impactful. We also identify which of the marketing (FT50) journals are at the forefront of cutting‐edge research and demonstrate their contributions to the progression of the most impactful topics in the field. Based on our findings, we identify key gaps and under‐researched areas of substantive interest, highlight impactful emerging topics in non‐marketing journals where marketing could offer unique perspectives, and provide concrete suggestions and directions to further progress and stimulate consumer research.
Sarcopenia and cardiovascular diseases: A systematic review and meta‐analysis
Authors: Zuo Xinrong , Li Xuehong , Tang Kuo , Zhao Rui , Wu Minming , Wang Yang , Li Tao
Published: April 2023

Sarcopenia is an age‐related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta‐analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non‐hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty‐eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28–42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23–41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49–72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2–85%) in patients with coronary artery disease, 30% (95% CI: 25–35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10–59%) in patients with congenital heart disease and 12% (95% CI: 7–17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9–17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high‐risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.
Tobacco use in Crohn's disease patients and association with disease outcomes in the United States Medicaid population, 2010–2019
Authors: Jasper Ryan A. , Chen Po‐Hung , Patel Reeha , Joseph Shelly , Miller Steven D. , Hutfless Susan
Published: April 2023

Background and Aim

To identify demographic factors associated with tobacco use in Crohn's disease (CD) patients in the US Medicaid population and examine how tobacco use affects disease outcomes.

Methods

We included Medicaid‐eligible patients who had ≥1 ICD code for CD, and 1 year of eligibility before and after the initial encounter. We used ICD codes to identify tobacco use with respect to the time of diagnosis and used logistic regression to identify the association between age, sex, and race with tobacco use at any point before diagnosis and after diagnosis, and determine the association of tobacco use before and after diagnosis on disease outcomes.

Results

We identified 98 176 eligible patients; 74.5% had no documented use of tobacco and 25.5% used tobacco at some point; 21.1% had used tobacco before their CD diagnosis and 11.8% had used tobacco after diagnosis. The population that used tobacco had a higher proportion of women, those who were White, non‐Hispanic, and those in their middle ages (21–60) than the group that did not use tobacco. Tobacco use before diagnosis resulted in higher risk of hospitalization and surgery (OR: 1.85 and 1.36, respectively).

Conclusion

Within the CD Medicaid population, tobacco use is more common in women than men, which differs from the general population, which is possibly a result of using diagnostic codes rather than survey data. Smoking cessation efforts should especially be directed at younger people who are at risk for CD, due to increased risk for more adverse outcomes among those who use tobacco before diagnosis.
Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies
Authors: Shields Adrian M. , Faustini Sian E. , Young Siobhan , Terjesen Sarah , McCarthy Nicholas I. , Anderson Rachel L. , Drayson Mark T. , Richter Alex G.
Published: April 2023

Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty‐five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato‐oncological diagnosis. Following immunological assessment and intervention, a 4.39‐fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30‐fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen‐specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen‐specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.