bluuebunny/crossref_metadata_2025 huggingface dataset:
Nifuroxazide enhances radiotherapy efficacy against hepatocellular carcinoma by upregulating PD-L1 degradation via the ubiquitin-proteasome pathway
Authors: Zhao Tiesuo , Wei Pengkun , Zhang Congli , Zhou Shijie , Guo Shuoshuo , Cheng Sichang , Gan Zerui , Xia Yuanling , Zhang Yongxi , Guo Sheng , Zhong Jiateng , Yang Zishan , Tu Fei , Wang Qianqing , Bai Jin , Ren Feng , Feng Zhiwei , Jia Huijie
Published: September 2023

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression.This study investigated the effects of Nifuroxazide on hepatocellular carcinoma using HepG2 cells and female C57BL/6 mice. HepG2 cells were irradiated and treated with different concentrations of Nifuroxazide, and various parameters were evaluated. Female C57BL/6 mice were divided into four groups and a hepatocellular carcinoma model was established. Each group received different treatments and observations were recorded. Spleens and tumor tissues were isolated from the mice and analyzed for tumor cell proliferation, apoptosis, and lymphocyte protein expression. T-cell subsets and the percentage of NK cells in the spleens were determined using flow cytometry.Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis
in vitro
. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.
Serotypes, virulence factors and multilocus sequence typing of Glaesserella parasuis from diseased pigs in Taiwan
Authors: Wu Ching-Fen , Hsu Chia-Yu , Chou Chi-Chung , Wang Chao-Min , Huang Szu-Wei , Kuo Hung-Chih
Published: September 2023

Background

Glaesserella parasuis (G. parasuis) belongs to the normal microbiota of the upper respiratory tract in the swine, but virulent strains can cause systemic infections commonly known as Glässer’s disease that leads to significant economic loss in the swine industry. Fifteen serotypes of G. parasuis have been classified by gel immunodiffusion test while the molecular serotyping based on variation within the capsule loci have further improved the serotype determination of unidentified field strains. Serovar has been commonly used as an indicator of virulence; however, virulence can be significantly differ in the field isolates with the same serotype. To date, investigations of G. parasuis isolated in Taiwan regarding antimicrobial resistance, serotypes, genotypes and virulence factors remain unclear.

Methods

A total of 276 G.parasuis field isolates were collected from 263 diseased pigs at the Animal Disease Diagnostic Center of National Chiayi University in Taiwan from January 2013 to July 2021. Putative virulence factors and serotypes of the isolates were identified by polymerase chain reaction (PCR) and antimicrobial susceptibility testing was performed by microbroth dilution assay. Additionally, the epidemiology of G. parasuis was characterized by multilocus sequence typing (MLST).

Results

Serotype 4 (33.3%) and 5 (21.4%) were the most prevalent, followed by nontypable isolates (15.9%), serotype 13 (9.4%), 12 (6.5%), 14 (6.2%), 7 (3.3%), 1 (1.8%), 9 (1.1%), 11 (0.7%) and 6 (0.4%). Nine out of 10 putative virulence factors showed high positive rates, including group 1 vtaA (100%), fhuA (80.4%), hhdA (98.6%), hhdB (96.0%), sclB7 (99.6%), sclB11 (94.9%), nhaC (98.2%), HAPS_0254 (85.9%), and cirA (99.3%). According to the results of antimicrobial susceptibility testing, ceftiofur and florfenicol were highly susceptible (>90%). Notably, 68.8% isolates showed multidrug resistance. MLST revealed 16 new alleles and 67 new sequence types (STs). STs of these isolated G. parasuis strains were classified into three clonal complexes and 45 singletons by Based Upon Related Sequence Types (BURST) analysis. All the G. parasuis strains in PubMLST database, including strains from the diseased pigs in the study, were defined into two main clusters by Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Most isolates in this study and virulent isolates from the database were mainly located in cluster 2, while cluster 1 included a high percentage of nasal isolates from asymptomatic carriers. In conclusion, this study provides current prevalence and antimicrobial susceptibility of G. parasuis in Taiwan, which can be used in clinical diagnosis and treatment of Glässer’s disease.
clrDV: a differential variability test for RNA-Seq data based on the skew-normal distribution
Authors: Li Hongxiang , Khang Tsung Fei
Published: September 2023

Background

Pathological conditions may result in certain genes having expression variance that differs markedly from that of the control. Finding such genes from gene expression data can provide invaluable candidates for therapeutic intervention. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean.

Methods

Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data.

Results

Simulation results show that clrDV has false discovery rate and probability of Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than its closest competitors, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV successfully recovers multiple gene candidates that have been reported to be associated with Alzheimer’s disease.
Temporal multicriteria evaluation of the categories proposed by the ‘Democracy Index’ of the countries: a perspective based on the DARIA-TOPSIS Method
Authors: Pinochet Luis Hernan Contreras , Dos Santos Marcos , Pardim Vanessa Itacaramby , Gomes Carlos Francisco Simões
Published: September 2023

This article analyzes the criteria of the ‘Democracy Index’ in countries, from 2017-2022, published by ‘The Economist’, aiming for an objective and comparative evaluation using the DARIA-TOPSIS method for temporal multicriteria assessment. The DARIA-TOPSIS method identified that among the top five ranked countries, the four most democratic ones are Nordic countries, with only New Zealand included in third place. Furthermore, the social and institutional trust, crucial for citizen participation observed in C_3 (Political Participation), reflects the high quality of democracy. These countries consistently exhibit high voter turnout rates and foster an active civil society culture in political decisions, as identified in C_1 (Electoral Process and Pluralism). Moreover, the variability of utility function values was better captured by the DARIA-TOPSIS method compared to a ranking based on average performance values (TOPSIS). However, the final order obtained by the methods generally coincides with or is very close.
Sustentabilidade em jogo – a corrida de obstáculos na contratação pública sustentável
Authors: Santiago Adelquis Stanley Monteiro , Moita Neto José Machado , De Souza Calebe Paiva Gomes
Published: September 2023

Este Caso para Ensino relata os desafios enfrentados por Jonas e sua equipe em um órgão ambiental na implementação de Contratações Públicas Sustentáveis. Inspirado em fatos, o Caso destaca os obstáculos encontradas pelo Poder Público na busca por soluções sustentáveis em suas contratações, com base na literatura científica. A narrativa apresenta reflexões teóricas e práticas sobre o desenvolvimento de soluções de sustentabilidade na contratação pública, o que o torna uma ferramenta valiosa para cursos de pós-graduação stricto sensu e latu sensu em diversas áreas, bem como para disciplinas de graduação em Administração, Administração Pública ou Gestão Pública que envolvam licitações e contratos. O objetivo do Caso para Ensino é contribuir para o debate sobre o papel do setor público na promoção de práticas sustentáveis em suas contratações, ressaltando a importância da adoção de critérios e indicadores de sustentabilidade em todas as etapas do processo de contratação. Por fim, o caso destaca a importância do engajamento e da capacitação dos agentes públicos para a implementação de políticas de sustentabilidade nas contratações públicas.
Estado do conhecimento: o ensino híbrido no contexto da educação superior
Authors: De Almeida Edson Rodrigo , Vieira Vania Maria de Oliveira
Published: September 2023

Este artigo apresenta uma pesquisa denominada “Estado do Conhecimento” sobre a temática “Ensino Híbrido”. Objetiva encontrar subsídios teóricos para um novo estudo, no sentido de não só compreender melhor a temática, como também buscar auxílio para decisões metodológicas de uma pesquisa maior.  As buscas foram realizadas nas plataformas BDTD e Google Scholar, a partir do termo indutor “Ensino Híbrido”. Após a utilização de alguns filtros, dentre eles o recorte temporal entre 2015 e 2020, foram encontradas 415 produções e destas foram selecionadas 21 para compor o corpus do “Estado do Conhecimento”. Os resultados mostram que a maioria das pesquisas associa o ensino híbrido à formação de professores, considerando o desenvolvimento de habilidades ligadas às tecnologias de informação.  Assim, tanto a formação de professores quanto as habilidades para lidar com as tecnologias passam a ser questões norteadoras para a pesquisa maior.
Effect of Nitrogen Management on Growth Attributes and Yield Attributes of Wheat
Authors: Vishwajna Rashmi R. , Debbarma Victor , Shingare Mahesh Namdev
Published: September 2023

A field experiment was conducted during rabi 2022-23 at Crop Research Farm, Department of Agronomy, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj (U.P) to determine the “Effect of Nitrogen management on growth and yield of wheat”. There were nine treatments each replicated thrice and the experiment was laid out in Randomized Block Design. The results showed that treatment 6 (75% N through urea + 25 % N through poultry manure) recorded significantly higher plant height (119.20 cm), maximum number of tillers/ m2 (214), higher plant dry weight (64.34 g), highest Crop growth rate during the interval of 50-75 DAS (35.73 g/m2/day), maximum number of effective tillers/ m2 (144.5), maximum number of grains/ spike (53.33) and highertest weight (97.71 g) compared to other treatments.
The Impact of Tariffs on Nigerian Economy (2000-2020)
Authors: Okechukwu Nwokoye Mathew , Okoye Machi Ignatus , Nkechi Irene Onwuka , Chika Ekwugha Juliet
Published: September 2023

This study examined the impact of tariffs on Nigeria's economic growth. It examines the extent to which tariffs have contributed to economic growth in Nigeria in 2000-2020. Tariffs, which are a form of tax or trade restrictions imposed on imported goods to discourage fledgling industries from international competition, can boost economic growth. The Ordinary Least Squares regression method was used to analyze the relationship between tariffs and economic growth. An econometric analysis was also used to determine the impact of tariff and other variables such as trade openness and exchange rate on economic growth in Nigeria. The results of the regression result showed that tariffs have a positive, statistically significant impact on economic growth in Nigeria. It was recommended that a trade policy be designed to improve the imposition of tariffs in Nigeria.
Barriers to Care Among Sexual and Gender Minority Individuals With Chronic Inflammatory Skin Diseases in the US
Authors: Nock Michael R. , Kamal Kanika , Zampella John G. , Roberson Mya L. , Cohen Jeffrey M. , Barbieri John S.
Published: September 2023

Importance

Research on the prevalence of barriers to care among sexual and gender minority (SGM) patients with chronic inflammatory skin diseases (CISDs) in the US is limited.

Objective

To compare the prevalence of cost and noncost barriers to care among SGM and non-SGM patients with CISDs and to analyze the prevalence of barriers based on SGM status and race and ethnicity.

Design, Setting, and Participants

A cross-sectional study of health care access and utilization survey data collected by the National Institutes of Health’s All of Us Research Program between May 31, 2017, and July 1, 2022, was conducted. Participants were adults aged 18 years or older with CISDs who enrolled in All of Us directly online or through partner health care practitioner organizations located across the US.

Exposures

Chronic inflammatory skin diseases, sexual orientation and gender identity, and race and ethnicity.

Main Outcome and Measures

The main outcome was the experience of cost and noncost barriers to health care among SGM patients with CISDs. Multivariable logistic regression was used to examine the association of SGM status with experiencing barriers to care.

Results

This study included 19 743 patients with CISDs; 1877 were SGM patients (median age, 40.5 years [IQR, 28.7-57.9 years]; 1205 [64.2%] assigned female sex at birth) and 17 866 were non-SGM patients (median age, 57.1 years [IQR, 40.8-68.1 years]; 13 205 [73.9%] assigned female sex at birth). Compared with non-SGM patients, SGM patients with CISDs were significantly more likely to delay specialist care (adjusted odds ratio [AOR], 1.23; 95% CI, 1.03-1.47), mental health care (AOR, 1.62; 95% CI, 1.37-1.91), and filling a prescription (AOR, 1.30; 95% CI, 1.11-1.52) because of cost. In addition, SGM patients with CISDs were significantly more likely than non-SGM patients to delay care because of transportation issues (AOR, 1.49; 95% CI, 1.22-1.80) and not having a health care practitioner who shares the same background with regard to race and ethnicity, religion, native language, sexual orientation, and gender identity (AOR, 1.39; 95% CI, 1.19-1.62). Sexual and gender minority patients with CISDs were also significantly more likely than non-SGM patients to report not always being treated with respect by their health care practitioners (AOR, 1.47; 95% CI, 1.30-1.65).

Conclusions and Relevance

The findings of this cross-sectional study of survey data suggest that SGM patients with CISDs may be disproportionately affected by cost and noncost barriers to health care. Dermatologists and other health care practitioners caring for SGM patients with CISDs have an important role in helping to address these barriers and larger systemic issues for SGM patients at both the patient and system levels.
Multi‐narrow type obstacle avoidance algorithm for UAV swarm based on game theory
Authors: Lin Ye , Na Zhenyu , Liu Jialiang , Lin Yun
Published: September 2023

A Flocking obstacle avoidance algorithm based on the extensive game with perfect information is proposed for the blockage problem of UAV swarm in front of multi‐narrow type obstacles. The two UAVs closest to the target are selected as participants of the game, and the game tree is defined to determine the combination of the motion strategies of the two UAVs to obtain the payoff matrix. Determine the subgame perfect Nash equilibrium to get the optimal strategy, and give the UAVs different motion states respectively so as to ensure that the UAVs can successfully pass multi‐narrow type obstacles. Simulation results demonstrate that the proposed algorithm has a higher over‐hole rate in the case of the multi‐narrow type obstacle compared to the static game‐based Flocking obstacle avoidance algorithm.
Brain‐Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha‐Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease
Authors: Sela Mor , Poley Maria , Mora‐Raimundo Patricia , Kagan Shaked , Avital Aviram , Kaduri Maya , Chen Gal , Adir Omer , Rozencweig Adi , Weiss Yfat , Sade Ofir , Leichtmann‐Bardoogo Yael , Simchi Lilach , Aga‐Mizrachi Shlomit , Bell Batia , Yeretz‐Peretz Yoel , Or Aviv Zaid , Choudhary Ashwani , Rosh Idan , Cordeiro Diogo , Cohen‐Adiv Stav , Berdichevsky Yevgeny , Odeh Anas , Shklover Jeny , Shainsky‐Roitman Janna , Schroeder Joshua E. , Hershkovitz Dov , Hasson Peleg , Ashkenazi Avraham , Stern Shani , Laviv Tal , Ben‐Zvi Ayal , Avital Avi , Ashery Uri , Maoz Ben M. , Schroeder Avi
Published: September 2023

Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain‐targeted liposomes (BTL) enhance the delivery of mAbs across the blood‐brain‐barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin‐receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha‐synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100‐nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.
Rational Design of a TADF Emitter with Steric Shielding and Multiple Resonance for Narrowband Solution‐Processed OLEDs
Authors: Peethani Nagaraju , Kwon Na Yeon , Koh Chang Woo , Park Su Hong , Ha Jung Min , Cho Min Ju , Woo Han Young , Park Sungnam , Choi Dong Hoon
Published: September 2023

Multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters exhibit enormous potential for use in organic light‐emitting diodes (OLEDs), owing to their exceptional external quantum efficiencies (EQEs) and narrowband emission spectra. However, planar MR‐TADF emitters often suffer from aggregation‐caused quenching (ACQ) and spectral broadening at high doping concentrations because of strong interchromophore π–π interactions. A method of sterically encapsulating the planar MR skeleton with four bulky 9‐phenyl‐fluorene (Fl) units is devised, resulting in the development of a bright bluish‐green emitter (4FlCzBN). This steric shielding effectively reduces intermolecular interactions, suppresses ACQ, and improves solubility. Consequently, by utilizing 4FlCzBN as a doping‐insensitive MR emitter, solution‐processed OLEDs are fabricated with doping concentrations of 2–16 wt.%, and they show EQEs of 10.1–10.9% with a bandwidth of 28–30 nm. Furthermore, a TADF‐sensitizer‐based device using 4FlCzBN demonstrates a significantly reduced efficiency roll‐off while achieving an EQE of 12.2%. This is a remarkable improvement that overcomes the disadvantages that are difficult to achieve in previously reported MR‐TADF OLEDs. The current work provides valuable insights into the design of efficient MR‐TADF emitters with minimized aggregation and reduced efficiency roll‐off for solution processing.
Recent Advances in Sensor–Actuator Hybrid Soft Systems: Core Advantages, Intelligent Applications, and Future Perspectives
Authors: Han Chankyu , Jeong Yongrok , Ahn Junseong , Kim Taehwan , Choi Jungrak , Ha Ji‐Hwan , Kim Hyunjin , Hwang Soon Hyoung , Jeon Sohee , Ahn Jihyeon , Hong Jin Tae , Kim Jin Joo , Jeong Jun‐Ho , Park Inkyu
Published: September 2023

The growing demand for soft intelligent systems, which have the potential to be used in a variety of fields such as wearable technology and human‐robot interaction systems, has spurred the development of advanced soft transducers. Among soft systems, sensor–actuator hybrid systems are considered the most promising due to their effective and efficient performance, resulting from the synergistic and complementary interaction between their sensor and actuator components. Recent research on integrated sensor and actuator systems has resulted in a range of conceptual and practical soft systems. This review article provides a comprehensive analysis of recent advances in sensor and actuator integrated systems, which are grouped into three categories based on their primary functions: i) actuator–assisted sensors for intelligent detection, ii) sensor‐assisted actuators for intelligent movement, and iii) sensor‐actuator interactive devices for a hybrid of intelligent detection and movement. In addition, several bottlenecks in current studies are discussed, and prospective outlooks, including potential applications, are presented. This categorization and analysis will pave the way for the advancement and commercialization of sensor and actuator‐integrated systems.
EGCG‐LYS Fibrils‐Mediated CircMAP2K2 Silencing Decreases the Proliferation and Metastasis Ability of Gastric Cancer Cells in Vitro and in Vivo
Authors: Dong Jiaqi , Zheng Zhousan , Zhou Mi , Wang Yunfei , Chen Jiajie , Cen Junjie , Cao Tiefeng , Yang Taowei , Xu Yi , Shu Guannan , Lu Xuanxuan , Liang Yanping
Published: September 2023

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer‐related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome‐mediated degradation, which further mediates the activation of the AKT/GSK3β/epithelial‐to‐mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin‐3‐gallate‐lysozyme (EGCG‐LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG‐LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG‐LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post‐transcriptional gene silencing. In addition, EGCG‐LYS carrying si‐circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG‐LYS fibrils delivery system provides a new tool and approach for the treatment of GC.
Concentrated Ionic Fluids: Is There a Difference Between Chloride‐Based Brines and Deep Eutectic Solvents?
Authors: Zante Guillaume , Elgar Christopher E. , George Katherine , Abbott Andrew P. , Hartley Jennifer M.
Published: September 2023

Deep Eutectic Solvents (DESs) have been lauded as novel solvents, but is there really a difference between them and concentrated aqueous brines? They provide a method of adjusting the activity of water and chloride ions which can affect mass transport, speciation and reactivity. This study proposes a continuum of properties across concentrated ionic fluids and uses metal processing as an example. Charge transport is shown to be governed by fluidity and there is no discontinuity between molar conductivity and fluidity irrespective of cation, charge density or ionic radius. Diffusion coefficients of iron(III) and copper(II) chloride in numerous concentrated ionic fluids show the same linear correlation between diffusion coefficient and fluidity. These oxidising agents were used to etch copper, silver and nickel and while the etching rate increased with fluidity for copper, etching of silver and nickel only occurred at high chloride and low water activity as passivation occurred when water activity increased. Overall, brines provide a high chloride content at a lower viscosity than DESs, but unlike DESs, brines are unable to prevent passivation due to their high water content. The results show how selective etching of mixed metal waste streams can be achieved by tuning chloride and water activity.
Production of healthier palm‐based edible oil blends and enzymatic interesterified structured lipids for cooking and trans‐free fat formulation applications
Authors: K. N. Prasanna Rani , Kaki Shiva Shanker , K Kezia Rani , B Kranthi Kumar , E Anjaneyulu , A Thirupathi , Prabhavathi Devi B. L. A.
Published: September 2023

Present study aimed to prepare palm‐based blends with edible oils to obtain healthier smart blends with a desired fatty acid profile of SAFA:MUFA:PUFA ratios as established by international health authorities for potential use in cooking and trans‐free fat formulation applications. Several blends of palm olein (POo), super olein (SOo) and palm stearin (PS) with sunflower (SFO), soybean (SBO), rice bran (RBO), mustard (MO), olive (OO) and sesame (SMO) oils were prepared in different mass (wt/wt) ratios. Among the prepared blends, the 6:4 POo:SFO, 1:1/6:4 POo:SBO, 6:4 SOo:SBO and 4:6 PS:RBO/SMO blends; 2:8 POo:RBO, 6:4 SOo:SFO blends and 1:1/6:4 POo:SMO, 1:1/6:4 POo:RBO, 6:4 SOo:SMO blends were found to have the balanced fatty acid profiles closer to AHA/JMHW/WHO recommended SFA:MUFA:PUFA ratios of 1:1:1/1:1.5:1/1:1.5:0.7, respectively. In addition, the 1:1/6:4 POo:SBO and 6:4 SOo:SBO blends also fulfilled the required ω‐6/ω‐3 ratios of 9.5 and 10.5 along with balanced fatty acid profile of 1:1:1 as per the nutritional guidelines. The 6:4 POo/SOo with SFO/SBO, 1:1 SOo:SMO and 4:6 PS:RBO/SMO smart blends were further processed for enzymatic interesterification (EIE) employing Lipozyme TLIM packed in a specially designed basket type stirrer (BTS) equipped in a bioreactor at 70°C with agitation speed of 390 rpm for 9 h to obtain trans‐free interesterified (IE) structured lipids (SLs) with desired physicochemical properties. This BTS technology helped to sustain the structure and morphology of the enzyme intact, and enable to process about 9 kg of the edible oil blends for IE with excellent recyclability and stability for 81 active hours.
The non‐ionizing electromagnetic stimulation enhanced antibody production (NESEAP) effect – Discovery and technological applications
Authors: Barbora Ayan , Rahamim Shmuel , Bohnick Maya , Firer Michael A. , Yahalom Asher
Published: September 2023

The rise of biological therapeutics in the global pharmaceuticals market has escalated the demand for quality monoclonal antibodies for healthcare and scientific applications. Reducing costs while enhancing production yields without compromising quality are the main challenges to the growth of this industry today. Over the last two decades non‐ionizing radiation has been demonstrated to elicit targeted biological responses in a frequency and dose dependent manner. We hypothesize and design a millimeter wave radiation procedure to enhance the yields of antibody‐producing hybridoma cell lines. We demonstrate this method enhances the production of IgA and IgG antibodies from MOPC315.BM and U13.6 cells by a factor of 24.05 ± 3.32 and 1.41 ± 0.03 respectively relative to untreated cells. No treatment associated cytotoxicity was observed in either cell line corroborating physiological viability of irradiated cells. Our results demonstrate proof‐of‐concept of a novel technique to significantly enhance antibody yields from hybridoma cells which could lead to a reduction in antibody production costs. Further studies will focus on scaling up of this technology and employment of non‐contact, tuned electromagnetic stimulation of biological systems for targeted responses.
The quality evaluation system of a famous traditional Chinese medicine Huaganjian decoction was established
Authors: Yu Wentao , Luo Man , Wu Huan , Li Junmao , Yang Shilin , Zhang Wugang , Yao Min , Feng Yunlin
Published: September 2023

Huaganjian decoction (HGJD) has been widely used clinically to treat liver injuries and gastritis. However, the quality evaluation system for HGJD is not perfect. In this study, paeoniflorin, hesperidin, geniposide, naringin, and quercetin were employed as quality markers. The quantitative analysis of these five components in HGJD was conducted using a high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry method. This method underwent validation for linearity, precision, accuracy, repeatability, and recovery. In summary, a reliable quantitative method was successfully employed to establish a comprehensive quality evaluation of HGJD.
How We Create Meaning: Introduction
Authors: Creekmore Laura S.
Published: September 2023

EDITOR'S SUMMARY

The Bulletin's special section on information architecture explores three noteworthy aspects of creating meaning and designing information. Kate Garklavs explains voice and tone in writing, discussing how consistently conveying personality and values can enhance the user experience in information architecture. Victor Yocco and Ashley Pulli explore social math as a method to inform through a visual story, making complex data understandable, meaningful and compelling. Dan Klyn analyzes two disparate works to demonstrate how internal comparison can shed light on the evolution and information architecture of a piece. The articles of the special section offer intriguing new insights into information architecture.
A Comparison in Pursuit of “The Masterworks of Information Architecture”: Learning from James Joyce's Ulysses and Richard Saul Wurman's The City, Form and Intent
Authors: Klyn Dan
Published: September 2023

EDITOR'S SUMMARY

In a search for classic works on information architecture, Joyce's Ulysses and Richard Saul Wurman's The City, Form and Intent are each compared internally across different versions and considered in terms of content, context and user. Each author modified readers' experiences through changes in the content and physical form of their works. Wurman's 1963 work, a loose‐leaf collection reflecting architecture through clay models of cities, was redone in 1974 with the same content but different physical presentation. Joyce's Ulysses was marked by variations across versions, with omissions, additions and typographic errors carried inconsistently through editions, leaving the author's intended meaning ambiguous. The context of Wurman's work was the very early stage in the author's career. The context of production of Ulysses involved composition, editing, publishing, correction and republishing across multiple channels, making consideration of the totality of the editions key to understanding the information architecture of the work. Users of Wurman's original print work exalted it, while users of a 2014 spin‐off web project see it from a different perspective. Similarly, the user experience for Ulysses varies widely, depending largely on which edition is read. The analysis and internal comparison of the two works highlight the importance of both content knowledge and technical skill throughout any information architecture project. Whether they will serve as masterworks for the field remains an open question.
Individualized Use of 6‐Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial
Authors: Zhou Yue , Wang Li , Sun Li‐Rong , Zhang Li , Wang Hong‐Mei , Liu Xi‐Ting , Yang Fan , Wu Ke‐Liang , Liang Yu‐Li , Zhao Bei‐Bei , Zhuang Yong , Fu Jin‐Qiu , Song Chao , Li Yun , Wang Ling‐Zhen , Xu Hui‐Juan , Gu Yan , van den Anker John , Ju Xiu‐Li , Zhu Xiao‐Fan , Zhao Wei
Published: September 2023

Continuous 6‐mercaptopurine (6‐MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose‐limiting hematopoietic toxicity. However, evidence‐based guidelines for gene‐based 6‐MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open‐label, active‐controlled clinical trial randomly assigned Chinese children with low‐ or intermediate‐risk ALL in a 1:1 ratio to receive TPMT–NUDT15 gene–based dosing of 6‐MP (N = 44, 10 to 50 mg/m2/day) or standard dosing (N = 44, 50 mg/m2/day) during maintenance therapy. The primary end point was the incidence of 6‐MP myelosuppression in both groups. Secondary end points included frequencies of 6‐MP hepatotoxicity, duration of myelosuppression and leukopenia, event‐free survival, and steady‐state concentrations of active metabolites (6‐thioguaninenucleotides and 6‐methylmercaptopurine nucleotides) in erythrocytes. A 2.2‐fold decrease in myelosuppression, the primary end point, was observed in the gene‐based–dose group using ~ 50% of the standard initial 6‐MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene‐based–dose group had a significantly lower risk of developing thiopurine‐induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady‐state concentrations of active metabolites in erythrocytes between the two groups. TPMT‐ and NUDT15‐based dosing of 6‐MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.
Metabolite profiling of a high protein fast neutron soybean mutant revealed increased storage of methionine and flavonoids
Authors: Islam Nazrul , Krishnan Hari B. , Jones Janice C. , Natarajan Savithiry
Published: September 2023

In this study, we used mass spectrometry (MS)‐based techniques to assess the metabolic profile of fast neutron–radiated soybean (Glycine max) seeds that had higher protein content. This mutant showed 1743 gene duplication compared to its non‐mutated counterpart. The metabolic profiling of soybean seeds identified 629 metabolites, of which 95 exhibited increased abundance and 127 exhibited decreased abundance in the mutant. The mutant showed an increase in several sulfur (S)‐containing metabolites, such as S‐methymethionine, methionine, and cysteine. Additionally, several secondary metabolites, such as cosmosiin and apigenin, increased significantly. The integration of metabolomics data and the duplicated genes on the global metabolic pathways revealed several duplicated genes on glycolytic, aspartate, and methionine metabolic pathways that might have contributed to the increased S‐metabolites in the seeds. We anticipate that the cascade effect of gene duplication discovered by metabolic profiling, along with information gleaned from gene expression, can be used to produce functional traits for soybean that add value to the soybean seeds.
Striving for sustainable development: Green financial policy, institutional investors, and corporate ESG performance
Authors: Lei Xiaodong , Yu Jianglong
Published: September 2023

Environmental, social, and governance (ESG) practices play an increasingly important role in achieving sustainable development goals. Drawing on institutional theory, this paper empirically explores whether and how green financial policy affects corporate ESG performance. Taking China's pilot policy for green finance reform and innovation (GFP) as a quasi‐natural experiment, we employ the difference‐in‐differences model to investigate the causal relationship between green financial policy and corporate ESG performance. We find that the GFP significantly improves corporate ESG performance. The results are robust to a series of checks such as parallel trend examination, placebo test, mitigation of omitted variable bias, alternative variables, and the exclusion of contemporaneous policies. The heterogeneity analysis shows that the positive impact of GFP on corporate ESG performance is more pronounced for firms with tighter financial constraints, higher agency costs, and more external pressures. On this basis, we further document that the positive impact of GFP on corporate ESG performance is more pronounced for investee firms with more institutional ownership. The above findings indicate that the formal institution of government‐led green financial policy can positively affect corporate ESG performance, and market participants‐institutional investors help to strengthen this policy effect. Overall, our study sheds light on the significant role of green financial policy in promoting corporate sustainability.
Benzothiadiazolyl‐pyridine and ‐2,2′‐bipyridine Ligands for Luminescent and Magnetic Complexes
Authors: Plyuta Nataliya , Cauchy Thomas , Julve Miguel , Avarvari Narcis
Published: September 2023

Two new luminescent ligands, 4‐(2‐pyridine)‐7‐methyl‐2,1,3‐benzothiadiazole (L1) and 4‐(2,2‐bipyridine)‐7‐methyl‐2,1,3‐benzothiadiazole (L2), based on 2,1,3‐benzothiadiazole and pyridine or bipyridine were obtained by Suzuki coupling reactions. DFT and TD‐DFT type calculations have been performed on L1 and L2 in order to assign their experimental UV‐visible and emission bands. Reaction of L1 and L2 with metal(II) chlorides (M=Zn, Mn, Cu) provided the neutral complexes of formulas [ZnL1Cl2] (1), [Zn(L1)2Cl2] (2), [ZnL2Cl2] (3), [MnL2Cl2] ⋅ 0,5CH2Cl2 (4) and [CuL2Cl2] ⋅ H2O (5) which have been structurally characterized. The Zn(II) ions in 1 and 2 are four‐coordinate in somewhat distorted tetrahedral N2Cl2 surroundings with L1 adopting bidentate (1) and monodentate (2) coordination modes. Complexes 3–5 are isostructural and their metal atoms are five‐coordinate in distorted square pyramidal environments with three nitrogen atoms from the tridentate L2 ligand and a chlorine building the basal plane and another chlorine atom occupying the apical position. The three Zn(II) complexes are strongly luminescent in solution and the solid state, while the cryomagnetic study of the paramagnetic compounds 4 and 5 in the temperature range 2.9–300 K shows a Curie‐Weiss behaviour typical of small antiferromagnetic interactions which are mediated by weak intermolecular contacts.
Diagnostic performance of inflammatory biomarkers and cytological analysis in salivary gland tumors
Authors: Abbate Vincenzo , Barone Simona , Borriello Gerardo , Troise Stefania , Bonavolontà Paola , Pacella Daniela , Vaira Luigi Angelo , Turri‐Zanoni Mario , Cuéllar Carlos Navarro , Califano Luigi , Dell' Aversana Orabona Giovanni
Published: September 2023

Background

This study aimed to evaluate the diagnostic performance of serum inflammatory biomarkers in salivary gland tumors with dubious results following cytological analysis.

Methods

A retrospective analysis of 239 cases following surgery between January 2011 and June 2022 was performed. Receiver Operating Characteristic curves were drawn and areas under the curves were computed to evaluate the diagnostic performance of the inflammatory biomarkers (SII, SIRI, PLR, and NLR). Optimal cut‐offs for each marker were determined by maximizing the Youden index.

Results

Analysis showed that among the major biomarkers examined, SIRI performed an AUC of 0.77. The best SIRI cut‐off was 0.94 with an accuracy of 79.9%. The accuracy, sensitivity, and specificity of cytological analysis were 77.8%, 59.6%, and 90.7% respectively. By combining SIRI with cytological analysis we demonstrated an increase in sensitivity to 82.8%.

Conclusions

Inflammatory biomarkers could be evaluated to support the diagnosis and treatment of salivary gland tumors in difficult cases.
Recent Applications of Paired Electrolysis in Organic Synthesis
Authors: Jiao Ke‐Jin , Gao Xiao‐Tong , Ma Cong , Fang Ping , Mei Tian‐Sheng
Published: September 2023

Recent years have witnessed a renaissance of organic electrochemistry since the cheap, safe, sustainable electron could be employed as a traceless redox agent to facilitate redox conversions. Additionally, divergent selectivity could be achieved by tuning the potential or current of the electrochemical reaction. Compared to electrooxidation or electroreduction reactions, paired electrolysis represents a more practical and energy‐efficient strategy that delivers the products by making use of both anodic and cathodic reactions simultaneously. This mini‐review summarized the breakthroughs and recent advances in this fascinating field and mainly is divided into three parts: parallel, sequential, and convergent paired electrolysis.
A Bridge Blueprint to Span the Chasm Between Research and Engineering — A Framework for Systems Engineering in Early‐Stage Research and Development
Authors: Hodges Ann , Granados Arno
Published: September 2023

Researchers and funding organizations often do not understand the value of systems engineering in early‐stage projects (technology readiness levels TRL 1‐5), during which systems engineering may be viewed as an unnecessary cost, and as a process heavy effort applicable only for mature technologies. This may result in a relative lack of engineering rigor and lack of understanding of innovation context which often contributes to failures in the “valley of death” between fundamental research and applied development.

We argue there is more than one pathway for crossing the valley of death, and that relevant application of systems engineering implemented at an appropriate level of rigor provides a foundation for transition and use of technical innovation. This article discusses the principles and foundational elements necessary for development and use of a framework for systems engineering applicable in early‐stage research and development (ESR&D), including tailoring considerations associated with TRL and stakeholder roles. Associated framework metrics are suggested to enable evaluation and practical implementation of the framework for systems engineering innovation management at this phase of technology development.
Pharmacoepidemiology of Ciprofloxacin: Analysis of Use Patterns and Cost Impact
Authors: Marchbanks C. Randall , Graham Kathleen K. , Barnes Jill , Dudley Michael N.
Published: September 2023

The pharmacoepidemiology and cost impact of ciprofloxacin use were evaluated after unrestricted availability in a 238‐bed community teaching hospital. The medical records on all patients treated with oral ciprofloxacin over 6 months were reviewed. To determine if the availability of ciprofloxacin altered antibiotic usage patterns and outcome variables, a group of control patients from a period prior to ciprofloxacin availability were matched and compared to patients who had received the drug. Ciprofloxacin was used as both initial and replacement for parenteral therapy in a variety of infections. A successful clinical outcome was achieved in approximately 90% of patients treated with ciprofloxacin and resulted in an estimated cost avoidance of approximately $165/course. However, comparisons with the matched‐control group revealed no differences in overall antibiotic costs or length of hospital stay. These results suggest that unrestricted availability of oral ciprofloxacin does not ensure changes in outcome variables related to cost. Educational and patient targeting programs may be necessary to promote earlier conversion of appropriate patients to newer oral therapies.
Dose Effectiveness and Safety of Butorphanol in Acute Migraine Headache
Authors: Elenbaas Robert M. , Iacono Carmine U. , Koellner Kay J. , Pribble John P. , Gratton Matthew , Racz Gabor , Evens Ronald P.
Published: September 2023

This study was undertaken to compare the effectiveness and safety of three dosage levels of butorphanol in 52 patients with acute, severe migraine headache. After baseline evaluation, patients were given a dose of butorphanol 1.0, 2.0, or 3.0 mg intramuscularly on a double‐blind basis. Assessments of pain intensity and pain relief using 100 mm linear analog scales (LAS), vital signs, and medication side effects were made at 15, 30, 45, and 60 minutes after the dose. All three treatment groups were similar in baseline characteristics. Each dose of butorphanol demonstrated a significant decrease in pain intensity LAS compared to baseline and increase in pain relief LAS over the observation period. The majority of analgesic response was observed at the first (i.e., 15‐min) assessment. Doses of 2.0 and 3.0 mg produced significantly greater analgesia than did 1.0 mg at all posttreatment evaluations. No significant difference was apparent between the 2.0‐ and 3.0‐mg doses. Adverse cardiovascular and respiratory depressant effects were not observed. An analgesic response to butorphanol 2.0 and 3.0 mg is clearly and rapidly evident and near maximum 30–45 minutes after administration. We conclude that in these doses butorphanol provides effective and safe analgesia for patients with acute migraine headache.
Androgen Regulation of Programmed Death of Normal and Malignant Prostatic Cells
Authors: ISAACS JOHN T. , LUNDMO PER I. , BERGES RICHARD , MARTIKAINEN PAULA , KYPRIANOU NATASHA , ENGLISH HUGH F.
Published: September 2023

ABSTRACT: Androgen‐dependent normal prostatic glandular cells and androgen‐dependent prostatic cancer cells can be induced to undergo cell death after androgen ablation. This death does not require the cells to proliferate and occurs as an energy‐dependent process collectively referred to as “programmed cell death” in which the cells actively commit “suicide.” Associated with this programmed cell death pathway is the enhanced expression of a series of genes and the fragmentation of the genomic DNA into nucleosomal oligomers. This genomic DNA fragmentation is the irreversible commitment step in the death of the cell and results from activation of Ca2 +/Mg2+‐ dependent endonuclease activity within the cell nucleus. This activation is due to sustained elevation of intracellular free Ca2+ (Cai) induced after androgen ablation. Metastatic prostatic cancer within an individual patient is heterogeneous, including both androgen‐dependent and ‐independent cancer cells. Thus, androgen ablation is rarely curative since it only induces the programmed death of the androgen‐dependent cancer cells without activating this pathway in the androgen‐independent cancer cells within the patient. Androgen‐independent prostatic cancer cells do not activate this death process after androgen ablation, since this does not induce a sustained increase in Cai. A new approach to treat androgen‐independent prostatic cancer cells has focused on the use of chemotherapeutic agents to induce a sustained increase in Cai. These studies demonstrate that if such a sustained elevation in Cai is maintained, even androgen‐independent prostatic cancer cells undergo programmed cell death.