bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐energy amplitude‐modulated electromagnetic field exposure: Feasibility study in patients with hepatocellular carcinoma
Authors: Capareli Fernanda , Costa Frederico , Tuszynski Jack A. , Sousa Micelange C. , Setogute Yone de C. , Lima Pablo D. , Carvalho Luciana , Santos Elizabeth , Gumz Brenda P. , Sabbaga Jorge , de Castria Tiago B. , Jardim Denis L. , Freitas Daniela , Horvat Natally , Bezerra Regis O. F. , Testagrossa Leonardo , Costa Tiago , Zanesco Tatiana , Iemma Antonio F. , Abou‐Alfa Ghassan K.
Published: May 2023

Background

Patients with advanced hepatocellular carcinoma (HCC) and poor liver function lack effective systemic therapies. Low‐energy electromagnetic fields (EMFs) can influence cell biological processes via non‐thermal effects and may represent a new treatment option.

Methods

This single‐site feasibility trial enrolled patients with advanced HCC, Child‐Pugh A and B, Eastern Cooperative Oncology Group 0–2. Patients underwent 90‐min amplitude‐modulated EMF exposure procedures every 2–4 weeks, using the AutEMdev (Autem Therapeutics). Patients could also receive standard care. The primary endpoints were safety and the identification of hemodynamic variability patterns. Exploratory endpoints included health‐related quality of life (HRQoL), overall survival (OS). and objective response rate (ORR) using RECIST v1.1.

Results

Sixty‐six patients with advanced HCC received 539 AutEMdev procedures (median follow‐up, 30 months). No serious adverse events occurred during procedures. Self‐limiting grade 1 somnolence occurred in 78.7% of patients. Hemodynamic variability during EMF exposure was associated with specific amplitude‐modulation frequencies. HRQoL was maintained or improved among patients remaining on treatment. Median OS was 11.3 months (95% confidence interval [CI]: 6.0, 16.6) overall (16.0 months [95% CI: 4.4, 27.6] and 12.0 months [6.4, 17.6] for combination therapy and monotherapy, respectively). ORR was 24.3% (32% and 17% for combination therapy and monotherapy, respectively).

Conclusion

AutEMdev EMF exposure has an excellent safety profile in patients with advanced HCC. Hemodynamic alterations at personalized frequencies may represent a surrogate of anti‐tumor efficacy. NCT01686412.
LPCAT1 enhances the invasion and migration in gastric cancer: Based on computational biology methods and in vitro experiments
Authors: Chen Zu‐Xuan , Liang Liang , Huang He‐Qing , Li Jian‐Di , He Rong‐Quan , Huang Zhi‐Guang , Song Rui , Chen Gang , Li Jian‐Jun , Cai Zheng‐Wen , Huang Jie‐An
Published: May 2023

Background and Aim

The biological functions and clinical implications of lysophosphatidylcholine acyltransferase 1 (LPCAT1) remain unclarified in gastric cancer (GC). The aim of the current study was to explore the possible clinicopathological significance of LPCAT1 and its perspective mechanism in GC tissues.

Materials and Methods

The protein expression and mRNA levels of LPCAT1 were detected from in‐house immunohistochemistry and public high‐throughput RNA arrays and RNA sequencing. To have a comprehensive understanding of the clinical value of LPCAT1 in GC, all enrolled data were integrated to calculate the expression difference and standard mean difference (SMD). The biological mechanism of LPCAT1 in GC was confirmed by computational biology and in vitro experiments. Migration and invasion assays were also conducted to confirm the effect of LPCAT1 in GC.

Results

Both protein and mRNA expression levels of LPCAT1 in GC were remarkably higher than those in noncancerous controls. Comprehensively, the SMD of LPCAT1 mRNA was 1.11 (95% CI = 0.86–1.36) in GC, and the summarized AUC was 0.85 based on 15 datasets containing 1727 cases of GC and 940 cases of non‐GC controls. Moreover, LPCAT1 could accelerate the invasion and migration of GC by boosting the neutrophil degranulation pathway and disturbing the immune microenvironment.

Conclusion

An increased level of LPCAT1 may promote the progression of GC.
Plasma lipid levels are associated with the CD8+ T‐cell infiltration and prognosis of patients with pancreatic cancer
Authors: Wu Bin , Shen Weiai , Wang Xiaoguang , Wang Jing , Zhong Zhengxiang , Zhou Zhongchen , Chen Xujian
Published: May 2023

Background

Recently, researchers have found that the tumour microenvironment plays an important role in tumours. We aimed to investigate the effects of plasma lipids on the prognosis of patients with pancreatic cancer and the infiltration of CD8+ T lymphocytes in tumour tissue.

Methods

We enrolled patients with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreatic surgery between 2012 and 2021. Clinical pathological data were recorded; total cholesterol (TC) and triglyceride (TG) levels were measured; and tissue samples were collected. A tissue microarray was generated using collected tissue samples, and CD8 staining was performed to determine immunoreactive scores (IRSs). The correlations of TC and TG levels with clinicopathological characteristics and prognosis were analysed. Finally, the correlations of TC and TG levels with CD8+ T‐cell infiltration were analysed.

Results

A total of 90 eligible PDAC patients were included. TC levels were significantly correlated with tumour grade and lymph node metastasis, and TG levels were significantly correlated with perineural invasion. The Kaplan–Meier survival analysis results indicated that the prognosis in the high TC group was significantly worse than that in the low TC group, and the prognosis in the high TG group was significantly worse than that in the low TG group. Cox multivariate analysis indicated that TC was an independent indicator of poor prognosis of pancreatic cancer patients after surgery. Spearman correlation analysis indicated that there were significant negative correlations between CD8 IRS and TC and between CD8 IRS and TG.

Conclusions

TC and TG levels are significantly related to the prognosis of pancreatic cancer patients. They may be associated with tumour progression to higher grades, lymph node metastasis and/or nerve invasion. More importantly, TC and TG may reduce CD8+ T lymphocyte infiltration into pancreatic cancer tissue, affecting antitumour immune functions and immunotherapy efficacy.
A Hairpin Ribozyme Derived Spliceozyme
Authors: Zhu Jikang , Hieronymus Robert , Müller Sabine
Published: May 2023

The vast majority of RNA splicing in today‘s organisms is achieved by the highly regulated and precise removal of introns from pre‐mRNAs via the spliceosome. Here we present a model of how RNA splicing may have occurred in earlier life forms. We have designed a hairpin ribozyme derived spliceozyme that mediates two RNA cleavages and one ligation event at specific positions and thus cuts a segment (intron) out of a parent RNA and ligates the remaining fragments (exons). The cut‐out intron then performs a downstream function, acting as a positive regulator of the activity of a bipartite DNAzyme. This simple scenario shows how small RNAs can perform complex RNA processing dynamics, involving the generation of new phenotypes by restructuring segments of given RNA species, as well as delivering small RNAs that may play a functional role in downstream processes.
Accurate Layer Spacing Matching of Polyoxometalate (POM) Anion‐based Ionic Liquids (ILs) to Promote PET Alcoholysis
Authors: Fang Pengtao , Zheng Xu , Zhang Ruiqi , Xu Junli , Yan Dongxia , Zhou Qing , Xin Jiayu , Shi Chunyan , Xia Shuqian , Lu Xingmei
Published: May 2023

Matching the active site of the catalyst with the carbonyl reactive site of PET at the nanoscale and achieve precise shearing of the PET reactive site at the molecular level by accurately modulating the catalyst layer spacing is particularly challenging. Herein, a new design strategy for green catalysts is proposed to synthesize a novel class of Polyoxometalate (POM) anion‐based ILs (POM‐ILs) [X]n[WZn3(H2O)2(ZnW9O34)2] (X=PyPs, Py, MIMPs, TEAPs, n=3, 6, 9, 12) with high thermally stable and adjustable layer spacing (1.00–1.63 nm). By adjusting the ratio of organic cations to match the spacing (1.34 nm) between the active sites of the catalyst with the spacing (1.32 nm) of the carbonyl functional groups on both sides of the PET benzene ring, the long PET chains were precisely sheared and rapidly degraded to bis(hydroxyethyl) terephthalate (BHET) in short time with the synergistic catalytic effect of anions and cations. Under the optimal conditions, the catalyst dosage was only 0.8 % of PET mass, and it could degrade 100 % in 30 min with BHET yield up to 85.35 %, and the yield of BHET was still greater than 85 % after 5 cycles. In addition, a possible mechanism of synergistic catalytic PET alcoholysis was proposed by density functional theoretical calculation. Moreover, the strategy of promoting PET alcoholysis by accurately modulating the spacing of the catalytic active site has not been reported.
Enantioselective Synthesis of Isoindolones via Palladium – Catalyzed Intramolecular Heck‐Mizoroki Reactions of Endocyclic Enamides Using N,N‐Ligands
Authors: Wiethan Carson , Braga Ingredy B. , Menezes da Silva Vitor H. , Batista João M. , Correia Carlos Roque D.
Published: May 2023

The enantioselective synthesis of isoindolones via Heck‐Mizoroki reactions of endocyclic enamides using a palladium‐bis(oxazoline) catalyst system is described. The N,N‐ligands, which are under‐represented in palladium‐catalyzed reactions involving aryl halides, proved to be an effective and low‐cost alternative to their phosphine‐based chiral ligand counterparts. The intramolecular Heck reaction of aryl iodides and endocyclic enamides enabled the construction of tricyclic isoindolones containing tertiary and quaternary chiral centers under mild conditions in yields up to 73 % and enantiomeric ratios up to 97 : 3. Vibrational circular dichroism (VCD) was instrumental in determining the absolute configuration of the enantioenriched isoindolones.
An Efficient and Stable Electrocatalyst Derived from Ni−Mo−Co MOF for Methanol Oxidation Reaction
Authors: Zaman Neelam , Iqbal Naseem , Noor Tayyaba
Published: May 2023

The majority of methanol oxidation electrocatalysts are based on platinum‐group metals such as platinum, palladium, and ruthenium. However, their usage is restricted because of their high cost, scarcity, and carbon monoxide toxicity concerns. We devised a simple approach for preparing a nickel foam (NF) based electrode using in‐situ synthesis of metal organic framework, such as Co‐MOF/NF, Ni‐MOF/NF, Mo‐MOF/NF, NC‐MOF/NF, MC‐MOF/NF, NM‐MOF/NF, and NMC‐MOF/NF, as an efficient electrocatalyst for methanol oxidation to produce carbon dioxide and water. Catalysts were synthesized using a hydrothermal process. In methanol with alkaline electrolyte, the as‐prepared NMC‐MOF/NF catalysts had the highest current density response, such as 5641 mA/cm2, in contrast to other bimetallic and single metal‐based metal organic framework electrocatalysts supported on Ni foam. We also observed that the NMC‐MOF/NF could efficiently catalyze the oxidation of carbon monoxide while being relatively unaffected by it. After 20,000 seconds in methanol oxidation, NMC‐MOF/NF based electrode retained about 100 % of its initial activity. Following simple synthesis technique and the improved catalytic efficiency and stability of NMC‐MOF/NF, methanol can be used to generate energy‐efficient products such as hydrogen.
Substituted meta[n]Cycloparaphenylenes: Synthesis, Photophysical Properties and Host–guest Chemistry
Authors: Bernt Felix , Wegner Hermann A.
Published: May 2023

Breaking the centrosymmetry of [n]cycloparaphenylenes ([n]CPPs) by one meta connection, leads to bright emission in the typically non‐fluorescent smaller derivatives, conserving their size dependent emissive properties. Using the building block strategy for [n]CPPs, different nitrile substituted meta[n]CPPs (n=6, 8, 10) have been prepared. The nitrile substituent offers a convenient handle for functional group conversions (e.g., carboxylic acid, amide, aldehyde, as well as 1H‐tetrazole). Besides the synthetic work, the photophysical properties of these novel m[n]CPP derivatives have been characterized. Additionally, the host–guest ability of cyano‐m[10]CPP has been explored by studying its complexation with fullerene C60. These insights open new applications of meta[n]CPPs as fluorophore in synthetic organic chemistry, material sciences as well as biomedical research.
Photochemically Driven Nickel‐Catalyzed Carboxylative C−N Coupling: Scope and Mechanism**
Authors: Abid Seifallah , Quirion Kevin P. , Yang Yi , Tang Renhe , Mai Binh Khanh , Liu Peng , Tlili Anis
Published: May 2023

Herein we disclosed an unprecedented photochemically driven nickel‐catalyzed carboxylative Buchwald–Hartwig amination to access a wide range of aryl carbamate derivatives. This reaction is performed under mild condition of temperature and atmospheric pressure of CO2 starting from commercially available (hetero)aryl iodides/bromides derivatives and alkyl amines preventing the formation of hazardous and/or toxic waste. Moreover, preliminary mechanistic investigations including stochiometric experiments as well as DFT calculations allow us to shed light on the reaction mechanism.
An Organocatalytic and Stereoselective Vinylogous Domino Process towards Thiochromans
Authors: Milbeo Pierre , Lebrêne Arthur , Savchuk Mariia , Vo‐Thanh Giang , Oudeyer Sylvain , Beucher Hélène , Brière Jean‐François
Published: May 2023

A highly diastereoselective organocatalyzed domino vinylogous sulfa‐Michael‐aldol‐cyclocondensation (VMAC) reaction has been developed using alkylidene Meldrum's acid as dienes highlighting two vinylogous steps, an unprecedented sulfa‐1,6‐conjugate addition and a diastereoselective aldol reaction triggering a formal (4+2) cycloaddition. This work opens a new route towards bio‐relevant and original tricyclic thiochroman derivatives.
Development of a Dynamic Gray‐Box Model of a Fermentation Process for Spore Production
Authors: Winz Joschka , Assawajaruwan Supasuda , Engell Sebastian
Published: May 2023

Fermentation processes are difficult to describe using purely mechanistic relations as the underlying biochemical phenomena are complex and often not fully understood. In order to cope with this challenge, we developed an approach to augment standard dynamic model equations by data‐based components that are fitted to data using machine learning techniques, which results in dynamic gray‐box models. This methodology is applied here to the batch fermentation process of the sporulating bacterium Bacillus subtilis, using experimental data from a lab‐scale fermenter. The key step in developing the model is the estimation of a training set for the machine learning submodels. The quality of the resulting model is analyzed, and the predictions are compared with real data.
Convective heat transfer coefficient for the side‐wall in a fixed bed
Authors: Baliga Chinmay , Nikrityuk Petr
Published: May 2023

Fixed beds are widely used in the chemical and process industry due to their relatively simple yet effective performance. Determining the radial heat transfer at the wall in a fixed bed is crucial to predict the performance of columns. Heat transfer parameters often need to be obtained experimentally. Various Nusselt versus Reynolds correlations in literature show considerable scatter and discrepancies. The tube‐to‐particle diameter ratio and boundary conditions on the particle surface have been understood to affect heat transfer near the wall by virtue of influence on the near‐wall porosity and mixing. In this work, a fixed bed consisting of mono‐disperse particles is generated via gravity‐forced sedimentation modelling utilizing the discrete element method for a ratio of 3.3. The system is meshed and imported in a computational fluid dynamics (CFD) solver. Fluid inlet velocity is varied to get corresponding to the laminar and turbulent flow regimes. The particles are treated as boundaries with Dirichlet, Neumann, and Robin boundary conditions applied for the closure of energy balance. Another set of simulations is run with particles modelled as solids with varying thermal conductivities (). The heat flux and volume‐averaged fluid temperature calculated during post‐processing are used to determine the wall heat transfer coefficient and, subsequently, the wall Nu number. Fifteen versus correlations are compiled and analyzed. A new semi‐empirical correlation for the wall Nusselt number has been developed for a fixed bed packed with monodisperse spheres for and results compared with data published in literature. Additionally, the impact of buoyancy effect on the wall Nusselt number has been studied.
Edge computing: A systematic mapping study
Authors: Sakhdari Jalal , Zolfaghari Behrooz , Izadpanah Shaghayegh , Mahdizadeh Zargar Samaneh , Rahati Quchani Mahla , Shadi Mahsa , Abrishami Saeid , Rasoolzadegan Abbas
Published: May 2023

Edge computing is a new way of computing that uses resources at the edge of a network to solve the problem of communication delays in applications that require immediate responses. This field has received a lot of attention from the research community over the past few decades, leading to a significant increase in publications. To better understand the field, a systematic mapping study (SMS) was conducted using a three‐tier search method that involved defining quality criteria to extract relevant search spaces and studies. This resulted in the selection of 112 search spaces out of 805 and 1440 studies out of 8725. The SMS addressed 8 research questions to identify the main topics, architectures, techniques, and other important aspects of edge computing.
Analysis of Lysine Acetylation and Acetylation‐like Acylation In Vitro and In Vivo
Authors: Yan Kezhi , Mousavi Negar , Yang Xiang‐Jiao
Published: May 2023

Protein lysine acetylation refers to the covalent transfer of an acetyl moiety from acetyl coenzyme A to the epsilon‐amino group of a lysine residue and is critical for regulating protein functions in almost all living cells or organisms. Studies in the past decade have demonstrated the unexpected finding that acetylation‐like acylation, such as succinylation, propionylation, butyrylation, crotonylation, and lactylation, is also present in histones and many non‐histone proteins. Acetylation and acetylation‐like acylation serve as reversible on/off switches for regulating protein function while interplaying with other post‐translational modifications (such as phosphorylation and methylation) in a codified manner. Lysine acetylation and acetylation‐like acylation are important for regulating different cellular and developmental processes in normal and pathological states. Thus, the detection of such modifications is important for related basic research and molecular diagnostics. Traditionally, lysine acetylation is detected by autoradiography, but recent decades have seen great improvement in the quality of site‐specific antibodies against acetylation (or acetylation‐like acylation), thereby providing competitive alternatives to the use of radioactive acetate and acetyl‐coenzyme A for in vivo and in vitro labeling, respectively. This article describes protocols for the detection of lysine acetylation and acetylation‐like acylation with site‐specific antibodies to complement extant autoradiography‐based methods (Pelletier et al., 2017). © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Acylation assays in vitro

Basic Protocol 2: Determination of in vivo acylation
Combining Protein Conformational Diversity and Phylogenetic Information Using CoDNaS and CoDNaS‐Q
Authors: Escobedo Nahuel , Monzon Alexander Miguel , Fornasari María Silvina , Palopoli Nicolas , Parisi Gustavo
Published: May 2023

CoDNaS (http://ufq.unq.edu.ar/codnas/) and CoDNaS‐Q (http://ufq.unq.edu.ar/codnasq) are repositories of proteins with different degrees of conformational diversity. Following the ensemble nature of the native state, conformational diversity represents the structural differences between the conformers in the ensemble. Each entry in CoDNaS and CoDNaS‐Q contains a redundant collection of experimentally determined conformers obtained under different conditions. These conformers represent snapshots of the protein dynamism. While CoDNaS contains examples of conformational diversity at the tertiary level, a recent development, CoDNaS‐Q, contains examples at the quaternary level. In the emerging age of accurate protein structure prediction by machine learning approaches, many questions remain open regarding the characterization of protein dynamism. In this context, most bioinformatics resources take advantage of distinct features derived from protein alignments, however, the complexity and heterogeneity of information makes it difficult to recover reliable biological signatures. Here we present five protocols to explore tertiary and quaternary conformational diversity at the individual protein level as well as for the characterization of the distribution of conformational diversity at the protein family level in a phylogenetic context. These protocols can provide curated protein families with experimentally known conformational diversity, facilitating the exploration of sequence determinants of protein dynamism. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Assessing conformational diversity with CoDNaS

Alternate Protocol 1: Assessing conformational diversity at the quaternary level with CoDNaS‐Q

Basic Protocol 2: Exploring conformational diversity in a protein family

Alternate Protocol 2: Exploring quaternary conformational diversity in a protein family

Basic Protocol 3: Representing conformational diversity in a phylogenetic context
Logarithmic time encoding and decoding of integer error control codes
Authors: Radonjic Aleksandar , Vujicic Vladimir
Published: May 2023

One of the most important characteristics of all error control codes (ECCs) is the complexity of the encoding/decoding algorithms. Today, there are many ECCs that can correct multiple bit errors, but at the price of high encoding/decoding complexity. Among the rare exceptions are integer ECCs (IECCs), whose serial encoding/decoding algorithms run in O(n) time, where n is the codeword length. In this article, we show that IECCs can be encoded/decoded even faster, that is, that their parallel encoding/decoding algorithms have O(log2n) time complexity.
Effect of HER2‐targeted therapy on PDX and PDX‐derived organoids generated from HER2‐positive salivary duct carcinoma
Authors: Aoyama Jun , Nojima Yusuke , Sano Daisuke , Hirai Yuri , Kijima Natsumi , Aizawa Yoshihiro , Takada Kentaro , Hatano Takashi , Takahashi Hideaki , Nishimura Goshi , Oridate Nobuhiko
Published: May 2023

Background

We previously established a patient‐derived xenograft (PDX) model, patient‐derived organoids (PDOs), and PDX‐derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2‐positive SDC.

Methods

The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice.

Results

The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice.

Conclusion

For the first time, we demonstrated the efficacy of anti‐HER2 therapy in HER2‐positive SDC using preclinical models of SDC PDX and PDXO.
Do teacher instructional practices shape children's academic self‐concept and interest in mathematics and science? Evidence from TIMSS 2015
Authors: Kim Matthew H. , Sidney Pooja G.
Published: May 2023

Children possess different beliefs regarding their ability to succeed in math and science, as well as different levels of enjoyment and interest in these topics. These motivational processes are important because they often shape learning‐related behaviours which in turn predict academic outcomes, over and above previous performance. But, what are the potential sources of influence that could explain individual differences in children's academic self‐concept and interest in math and science? In this registered report, we adopted a situated expectancy‐value theory framework to examine the potential role of teacher instructional practices that emphasize conceptual understanding in enhancing these motivational processes. We focused on practices emphasizing conceptual understanding given science‐driven recommendations to implement them across the United States. Contrary to our hypotheses, a multilevel analysis of grade 4 U.S. data from the 2015 release of the Trends in International Mathematics and Science Study (TIMSS) revealed that the self‐reported frequency of instructional practices emphasizing conceptual understanding were unrelated to math or science self‐concept and interest. Our null findings prompt greater attention to other factors, such as the quality and implementation of instructional practices, differences between instructional goals and actual practices, and classroom composition, that could enhance ability beliefs and values in math and science.
Expression and significant roles of the lncRNA NEAT1/miR‐493‐5p/Rab27A axis in ulcerative colitis
Authors: Wang Hecheng , Teng Jiadan , Wang Mingtao , Zhang Yuhang , Liu Xiaoshuang , Liu Zhuya
Published: May 2023

Background

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to play regulatory roles in ulcerative colitis (UC). In this study, we aimed to determine the specific roles and action mechanism of the nuclear paraspeckle assembly transcript 1 (NEAT1) in UC.

Methods

Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was used to determine the lncRNA NEAT1 and miR‐493‐5p expression levels in patients with UC and healthy volunteers. We determine the forecast linkage points of NEAT1 and miR‐493‐5p using Starbase and those of miR‐493‐5p and Rab27A using TargetScan, and further verified them using a double luciferase gene reporter kit. RT‐qPCR and Western blot analysis were used to determine the lncRNA NEAT1, miR‐493‐5p, and Rab27A expression levels in lipopolysaccharide (LPS)‐induced Caco‐2 cells. Flow cytometry and cell counting kit‐8 were used to assess Caco‐2 cell viability. Tumor necrosis factor‐α, interleukin (IL)‐6, IL‐8, and IL‐1β levels were determined via an enzyme‐linked immunosorbent assay.

Results

Expression levels of NEAT1 were upregulated and those of miR‐493‐5p were downregualted in 10 ng/mL LPS‐treated Caco‐2 cells and patients with UC. Dual‐luciferase gene reporter assay revealed that miR‐493‐5p is linked to NEAT1, and Rab27A is a downstream target of miR‐493‐5p. Overexpression of miR‐493‐5p inhibited the apoptosis and inflammation in LPS‐treated Caco‐2 cells. Moreover, downregulation of lncRNA NEAT1 expression also inhibited the apoptosis and inflammation in LPS‐treated Caco‐2 cells, which was reversed by Rab27A plasmid cotransfection.

Conclusion

Our results revealed that NEAT1 participates in UC progression by inhibiting miR‐493‐5p expression.
Fisetin regulates the biological effects of rat nucleus pulposus mesenchymal stem cells under oxidative stress by sirtuin‐1 pathway
Authors: Zhou Qing , Zhu Chao , Xuan Anwu , Zhang Junyou , Zhu Zhenbiao , Tang Liang , Ruan Dike
Published: May 2023

Background

Excessive oxidative stress has been accepted as one of the critical factors for intervertebral disc degeneration (IDD), which is associated with low back pain (LBP). Fisetin (Fis) is a bioactive flavonoid that possesses strong bioactive activity. In present study, we aimed to illuminate the role of Fis on nucleus pulposus mesenchymal stem cells (NPMSCs).

Methods

NPMSCs were isolated and cultured from rat NP tissues and identified by flow cytometry and multilinear differentiation. The cytotoxicity of Fis, EX‐527, and hydrogen peroxide (H2O2) on NPMSCs was validated using Cell Counting Kit‐8 tests. Cell apoptosis was tested by flow cytometry and TUNEL assay. Inflammatory mediators were assessed by Elisa tests, RT‐PCR. Extracellular matrix (ECM) metabolism was measured by Western blot analysis and RT‐qPCR. The expression of the SIRT1 was evaluated by Western blot analysis.

Results

NPMSCs were successfully isolated and cultured from rat NP tissues, and it has been identified by flow cytometry and multilinear differentiation. The results showed that Fis attenuated H2O2‐induced apoptosis, inflammation, and ECM degradation of NPMSCs. Moreover, the above protective effects of Fis can be inhibited by EX‐527, a unique SIRT1 inhibitor, indicating that SIRT1 may involve in the mechanism of Fis in protecting NPMSCs from oxidative stress.

Conclusions

As a natural compound with little cytotoxicity on NPMSCs, Fis alleviate H2O2‐induced apoptosis, inflammation, and ECM degradation by suppressing oxidative stress, this finding may add the theoretical basis for research on new treatment of IDD based on NPMSCs.
To be appreciated or to be despised: The role of leader selection and trust in leaders
Authors: Gu Zibei , Cheng Nian , Chen Yanan
Published: May 2023

To sustainably develop organisational goals, it is important to create conditions under which leaders are trusted and judged to be incorrupt. We proposed that and tested whether leader selection affects judgements of leader corruption. A correlational study with cross‐national data and two experimental studies in China were conducted. Study 1 collected and analysed 20‐year panel data on 93 countries/territories. To provide causal evidence for the results of Study 1 and account for this effect, Studies 2 and 3 manipulated leader selection and measured trust in leaders and perceptions of leader corruption. The three studies converged to show that election (vs. appointment) predicted decreased judgements of leader corruption. Furthermore, Studies 2 and 3 identified that trust in leaders is the underlying mechanism driving this leader selection effect. Our findings contribute to a better understanding of perceptions of leader corruption, the process of leader empowerment and the control of corruption.
Quality management in anatomic pathology: The past, present, and future
Authors: Xi Chenguang , Cao Dengfeng
Published: May 2023

One of the challenges in anatomic pathology laboratories is to meet the increasing need for pathological diagnosis, using quality management (QM) activities and systems to ensure that patients receive their accurate and timely pathology report. The aim of this paper is to review anatomic pathology QM from both management and technical perspectives, including the past, present, and future opportunities. First, the evolution of the QM concept and scope will be discussed. Next, current QM system implementation and laboratory accreditations will be discussed from the management perspective, and common medical errors in anatomic pathology in different testing cycles will be analyzed. Finally, selected future management systems to improve the level of total QM worldwide for patient safety and the potential of informatics to be used as an auxiliary tool in anatomic pathology will be discussed.
Bone healing around implants placed in subjects with metabolically compromised systemic conditions
Authors: Bergamo Edmara T. P. , Witek Lukasz , Ramalho Ilana , Lopes Adolfo C. O. , Nayak Vasudev Vivekanand , Bonfante Estevam A. , Tovar Nick , Torroni Andrea , Coelho Paulo G.
Published: May 2023

The aim of this study was to evaluate the bone healing of tight‐fit implants placed in the maxilla and mandible of subjects compromised with metabolic syndrome (MS) and type‐2 Diabetes Mellitus (T2DM). Eighteen Göttingen minipigs were randomly distributed into three groups: (i) control (normal diet), (ii) MS (cafeteria diet for obesity induction), (iii) T2DM (cafeteria diet for obesity induction + Streptozotocin for T2DM induction). Maxillary and mandibular premolars and molar were extracted. After 8 weeks of healing, implants with progressive small buttress threads were placed, and allowed to integrate for 6 weeks after which the implant/bone blocks were retrieved for histological processing. Qualitative and quantitative histomorphometric analyses (percentage of bone‐to‐implant contact, %BIC, and bone area fraction occupancy within implant threads, %BAFO) were performed. The bone healing process around the implant occurred predominantly through interfacial remodeling with subsequent bone apposition. Data as a function of systemic condition yielded significantly higher %BIC and %BAFO values for healthy and MS relative to T2DM. Data as a function of maxilla and mandible did not yield significant differences for either %BIC and %BAFO. When considering both factors, healthy and MS subjects had %BIC and %BAFO trend towards higher values in the mandible relative to maxilla, whereas T2DM yielded higher %BIC and %BAFO in the maxilla relative to mandible. All systemic conditions presented comparable levels of %BIC and %BAFO in the maxilla; healthy and MS presented significantly higher %BIC and %BAFO relative to T2DM in the mandible. T2DM presented lower amounts of bone formation around implants relative to MS and healthy. Implants placed in the maxilla and in the mandible showed comparable amounts of bone in proximity to implants.
Dentoalveolar Alterations in an Adenine‐Induced Chronic Kidney Disease Mouse Model
Authors: Mohamed Fatma F. , Amadeu de Oliveira Flavia , Kinoshita Yuka , Yalamanchili Riti R. , Eltilib Leena A. , Andras Natalie L. , Narisawa Sonoko , Tani Takashi , Chu Emily Y. , Millán José Luis , Foster Brian L.
Published: May 2023

Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD–MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD–MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)‐induced CKD (AD–CKD) mouse model. Eight‐week‐old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high‐phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro–computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp‐dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue‐nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD–CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD‐associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Extracellular lncRNAs secreted and absorbed by cardiomyocytes
Authors: Jiang Xiaoying , Lei Ronghui
Published: May 2023

Exosomes are membrane‐surrounded extracellular vesicles released by almost all cell types, which mediate intercellular communications by delivering bioactive molecules from secretory cells to recipient cells. Long noncoding RNAs (lncRNAs) are a large class of non‐(protein)‐coding RNAs with lengths exceeding 200 nucleotides that are very active in the development of cardiovascular diseases (CVDs). Increasing evidence suggests that exosomal lncRNAs also play important roles in the progress of CVDs. We focus on the current available studies regarding these extracellular lncRNAs secreted and absorbed by cardiomyocytes and their functional roles in CVDs, hopefully providing a basis for deeper understanding of the pathological mechanisms of CVDs and their potential for clinical diagnosis and therapy.
A case of COVID‐19‐associated mucormycosis due to Lichtheimia ramosa
Authors: Aboutalebian Shima , Erami Mahzad , Momen‐Heravi Mansooreh , Charsizadeh Arezoo , Hezaveh Seyed Jamal Hashemi , Matini Amir Hassan , Ahsaniarani Amir Hossein , Fakhrehi Mojtaba , Mirhendi Hossein
Published: May 2023

Background

Mucormycosis is a life‐threatening invasive fungal infection in immunocompromised and COVID‐19 patients.

Case Report

Here, we report a fatal rhino‐orbito‐cerebral mucormycosis caused by Lichtheimia ramosa, in a 79‐year‐old diabetic female. She was initially admitted to the hospital for COVID‐19 infection and received broad‐spectrum antibiotics and corticosteroids. After 1 month, she was admitted again because of persistent headaches and decreased right eye movement when the computed tomography scan showed mucosal thickening and opacification of paranasal sinuses. Microbiological investigations, including culture and direct microscopy, and histopathological findings confirmed the diagnosis of proven mucormycosis. The isolated causal agent was identified as Lichtheimia ramosa by sequencing the entire ITS region of nuclear ribosomal DNA. Despite surgical debridement and administration of liposomal amphotericin B 5 mg/kg/day, the patient's level of consciousness suddenly deteriorated; she was intubated and mechanically ventilated in the ICU and died on the same day.

Conclusion

To our knowledge, this is the first worldwide case of COVID‐19‐associated rhino‐orbito‐cerebral mucormycosis due to Lichtheimia ramosa.
Virtual reality simulation of panoramic radiographic anatomy for dental students
Authors: Alsufyani Noura , Alnamlah Sarah , Mutaieb Sarah , Alageel Raseel , AlQarni Mayson , Bukhari Areej , Alhajri Maram , AlSubaie Abdulrahman , Alabdulkarim Meshari , Faden Asma'a
Published: May 2023

Purpose

This work aimed to utilize virtual reality (VR) in dental radiographic anatomical interpretation in junior dental students and test if it can enhance student learning, engagement, and performance.

Methods

VR software for panoramic anatomy was developed. Sixty‐nine first‐year dental students were divided into a control group (lecture‐based) and an experimental group (VR) to learn panoramic radiographic anatomy. Both groups were then tested on knowledge via a 20‐question quiz. Student feedback on VR experience was collected via an online survey.

Results

There was a statistically significant difference between lecture‐based and VR students in the correct identification of anatomical landmarks. Lecture‐based students scored higher in identifying the ear lobe, hyoid bone, condylar neck, and external oblique ridge, whereas VR students scored higher in identifying zygoma (Chi‐squared test, p < 0.005). The VR group reported high evaluation on all perception items of the online feedback survey on their experience (Student t‐test, p < 0.005).

Conclusions

Lecture‐based students generally showed better performance in panoramic radiographic anatomy. Several structures were not correctly identified in both groups of novice students. The positive feedback of VR experience encourages future implementation in education to augment conventional methods of radiographic anatomy in dentistry with considerations to repeated exposures throughout undergraduate dental education.
Electronic medical record documentation of germline genetic evaluations in patients with ovarian cancer
Authors: Batson Melissa , Goldblatt Lindsay G. , Pundock Stacy , Arutyunov Anna , McKenna Danielle , Haggerty Ashley , Symecko Heather , Shah Payal D.
Published: May 2023

Germline genetic evaluation is indicated for all patients with epithelial ovarian cancer (EOC). For testing to have clinical utility, results must be documented within the electronic medical record (EMR) and accessible to providers at the point of care, which can be challenging in the context of current EMR limitations and genetic testing processes. We examined the receipt of genetics services and EMR capture of genetic testing results in patients with EOC. We conducted a retrospective chart review to examine germline genetic evaluations among patients with EOC seen by a gynecologic or medical oncologist at the University of Pennsylvania in 2016. EMRs were reviewed to determine: (1) if patients were referred for genetic evaluation; (2) if genetic testing was performed; (3) if results were documented in office notes, scanned third‐party test reports, and/or the EMR problem list; (4) if provider notes correctly listed the variant classification. Overall, 413 (62%) of patients had documented genetic testing. Genetic testing was documented in almost all provider notes (96%) and the majority of scanned EMR reports (64%). Pathogenic variants were found in 119 (29%) individuals; the majority (70%) had genetic testing documented within EMR problem lists. Provider notes were highly accurate in describing variant classification. In this study, genetic testing was performed and documented in the EMR for most EOC patients. Approximately one‐third of those tested did not have scanned test reports specifying variant found, limiting the utility of test results for cascade testing and therapeutic decisions.
MRI Assessment of Brain Frailty and Clinical Outcome in Patients With Acute Posterior Perforating Artery Infarction
Authors: Duan Qi , Lyu Jinhao , Cheng Kun , Wang Xueyang , Meng Zhihua , Wu Xiaoyan , Chen Wen , Wang Guohua , Niu Qingliang , Li Xin , Bian Yitong , Han Dan , Guo Weiting , Yang Shuai , Bian Xiangbing , Lan Yina , Wang Liuxian , Zhang Tingyang , Duan Caohui , Tian Chenglin , Lou Xin ,   the MR‐STARS Investigators
Published: May 2023

Background

Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation.

Purpose

To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation.

Study Type

Prospective.

Population

One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion‐weighted magnetic resonance imaging (MRI)/time‐of‐flight MR angiography).

Field Strength/Sequence

T1‐ and T2‐weighted fast spin echo, T2‐weighted fluid‐attenuated inversion recovery, diffusion‐weighted echo planar, gradient echo (susceptibility‐weight imaging), and 3D time‐of‐flight MR angiography sequences at 3.0 T.

Assessment

Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion‐weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed.

Statistical Tests

Fisher's exact test, Mann–Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant.

Results

Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237–2.541).

Data Conclusion

Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI.

Level of Evidence

3

Technical Efficacy

Stage 3
COVID‐19 vaccines reduce mortality in hospitalized patients with oxygen requirements: Differences between vaccine subtypes. A multicontinental cohort study
Authors: Huespe Ivan A. , Ferraris Augusto , Lalueza Antonio , Valdez Pascual R. , Peroni Maria L. , Cayetti Luis A. , Mirofsky Matias A. , Boietti Bruno , Gómez‐Huelgas Ricardo , Casas‐Rojo José M. , Antón‐Santos Juan M. , Núñez‐Cortés Jesús M. , Lumbreras Carlos , Ramos‐Rincón Jose‐Manuel , Barrio Noelia G. , Pedrera‐Jiménez Miguel , Martin‐Escalante María D. , Ruiz Francisco R. , Onieva‐García María Á. , Toso Carlos R. , Risk Marcelo R. , Klén Riku , Pollán Javier A. , Gómez‐Varela David
Published: May 2023

The aim of this study was to analyze whether the coronavirus disease 2019 (COVID‐19) vaccine reduces mortality in patients with moderate or severe COVID‐19 disease requiring oxygen therapy. A retrospective cohort study, with data from 148 hospitals in both Spain (111 hospitals) and Argentina (37 hospitals), was conducted. We evaluated hospitalized patients for COVID‐19 older than 18 years with oxygen requirements. Vaccine protection against death was assessed through a multivariable logistic regression and propensity score matching. We also performed a subgroup analysis according to vaccine type. The adjusted model was used to determine the population attributable risk. Between January 2020 and May 2022, we evaluated 21,479 COVID‐19 hospitalized patients with oxygen requirements. Of these, 338 (1.5%) patients received a single dose of the COVID‐19 vaccine and 379 (1.8%) were fully vaccinated. In vaccinated patients, mortality was 20.9% (95% confidence interval [CI]: 17.9–24), compared to 19.5% (95% CI: 19–20) in unvaccinated patients, resulting in a crude odds ratio (OR) of 1.07 (95% CI: 0.89–1.29; p = 0.41). However, after considering the multiple comorbidities in the vaccinated group, the adjusted OR was 0.73 (95% CI: 0.56–0.95; p = 0.02) with a population attributable risk reduction of 4.3% (95% CI: 1–5). The higher risk reduction for mortality was with messenger RNA (mRNA) BNT162b2 (Pfizer) (OR 0.37; 95% CI: 0.23–0.59; p < 0.01), ChAdOx1 nCoV‐19 (AstraZeneca) (OR 0.42; 95% CI: 0.20–0.86; p = 0.02), and mRNA‐1273 (Moderna) (OR 0.68; 95% CI: 0.41–1.12; p = 0.13), and lower with Gam‐COVID‐Vac (Sputnik) (OR 0.93; 95% CI: 0.6–1.45; p = 0.76). COVID‐19 vaccines significantly reduce the probability of death in patients suffering from a moderate or severe disease (oxygen therapy).