bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandemic, a catalyst for change: Strategic planning for digital education in English secondary schools, before during and post Covid
Authors: Baxter Jacqueline , Floyd Alan , Jewitt Katharine
Published: December 2022

Following lockdowns in 2020 owing to Covid‐19, schools needed to find a way to ensure the education of their pupils. In order to do this, they engaged in digital learning, to varying extents. Innovations emanated from all school staff including, for example, teachers, leaders and teaching assistants. Some were already innovating in this area and brought forward and implemented digital strategies, while others engaged with digital learning for the first time. While research is emerging about the effects of the pandemic restrictions on pupils and staff in relation to key issues such as mental health and educational attainment, very little is known about the impact on school leaders' strategic planning processes. To address this gap, this paper draws on a UK Research and Innovation funded study adopting a strategy as learning approach to report on 50 qualitative interviews with school leaders to examine digital strategy in English secondary schools, before, during and after July 2021, when restrictions were lifted in England. It draws on strategy as learning literature to evaluate if schools have changed their strategic planning for digital learning, as a direct response to having learned and innovated during the pandemic. The paper concludes that there is evidence that digital innovations during the pandemic have changed the ways in which leaders think about their digital strategy, thus supporting a strategy as learning approach. However it also concludes that although there is ample evidence that the pandemic has changed the way many schools view digital learning, for some schools, there remain persistent barriers to digital integration and planning. These emanate both from material and cultural considerations, as well as leader vision and belief in digital learning.
The definition of corporate corruption prevention during the last decade: Bibliometrics and content data for the future research agenda
Authors: Ruggiero Pasquale , Mussari Riccardo
Published: December 2022

The purpose of this research is to provide a valuable study about the development of literature on corruption prevention during the last decade suggesting the way for the future agenda. We collected documents with the aims to develop a structured literature review (SLR). We collected 113 documents adopting a not grey analysis. Our results shows two main research areas: (i) the corruption prevention understanding its features and using accounting and ethical activities in the business and government procurement and (ii) anticorruption measures, disclosure and behaviours as renewed tools to increase corporate governance sustainability and corporate social responsibility. This is the first time for proposing the SLR on corporate corruption preventions and renewed models directed to build an updated background and emerging issues. This paper is original because proposes for the first time the literature collection of corporate corruption prevention's models providing valuable insights, critique and definition for the future research.
Selectivity Rule of Cryptands for Anions: Molecular Rigidity and Bonding Site
Authors: Li Jiayao , Wang Changwei , Mo Yirong
Published: December 2022

Cryptands utilize inside CH or NH groups as hydrogen bond (H‐bond) donors to capture anions such as halides. In this work, the nature and selectivity of confined hydrogen bonds inside cryptands were computationally analyzed with the energy decomposition scheme based on the block‐localized wavefunction method (BLW‐ED), aiming at an elucidation of governing factors in the binding between cryptands and anions. It was revealed that the intrinsic strengths of inward hydrogen bonds are dominated by the electrostatic attraction, while the anion preferences (selectivity) of inner CH and NH hydrogen bonds are governed by the Pauli exchange repulsion and electrostatic interaction, respectively. Typical conformers of cages are classified into two groups, including theC3(h)‐symmetrical conformers, in which all halide anions are located near the centroids of cages, and the “semi‐open” conformers, which exhibit shifted bonding sites for different halide anions. Accordingly, the difference in governing factors of selectivity is attributed to either the rigidity of cages or the binding site of anions for these two groups. In details, theC3conformers of NH cryptands can be enlarged more remarkably than theC3(h)‐symmetrical conformers of CH cryptands as the size of anion (ionic radius) increases, resulting in the relaxation of the Pauli repulsion and a dramatic reduction in electrostatic attraction, which eventually rules the selectivity of NH cryptands for halide anions. By contrary, the CH cryptands are more rigid and cannot effectively reduce the Pauli repulsion, which subsequently governs the anion preference. UnlikeC3conformers whose rigidity determines the selectivity, semi‐open conformers exhibit different binding sites for different anions. From F−to I−, the bonding site shifts toward the outside end of the pocket inside the semi‐open NH cryptand, leading to the significant reduction of the electrostatic interaction that dominates the anion preference. Differently, binding sites are much less affected by the size of anion inside the semi‐open CH cryptand, in which the Pauli exchange repulsion remains the key factor for the selectivity of inner hydrogen bonds.
Neoadjuvant famitinib and camrelizumab, a new combined therapy allowing surgical resection of the primary site for anaplastic thyroid carcinoma
Authors: Yang Shuwen , Ji Dongmei , Xue Fen , Chen Tongzhen , Wang Yu , Ji Qinhai
Published: December 2022

Background

Anaplastic thyroid cancer (ATC) is considered the most lethal thyroid cancer, with an overall 5‐year survival rate below 10%. The FDA approved a BRAF/MEK inhibitor combination for the treatment of patients with BRAF‐mutated ATC. However, effective therapeutic options for patients with wild‐type BRAF are lacking.

Case

In our phase II study, patients having advanced/metastatic solid ATCs were treated with famitinib and camrelizumab, a combination therapy involving a multi‐targeted kinase inhibitor and an anti‐PD‐1 antibody. We report a case of a patient with locally advanced unresectable ATC who underwent this combination therapy, allowing us to perform complete surgical resection followed by post‐operative radiation therapy.

Conclusion

To the best of our knowledge, this is the first report describing the use of famitinib and camrelizumab as a neoadjuvant treatment for ATC with wild‐type BRAF. Clinical trial for a novel neoadjuvant approach for ATC are currently open for enrollment.
Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues
Authors: Porwit Anna , Béné Marie C. , Duetz Carolien , Matarraz Sergio , Oelschlaegel Uta , Westers Theresia M. , Wagner‐Ballon Orianne , Kordasti Shahram , Valent Peter , Preijers Frank , Alhan Canan , Bellos Frauke , Bettelheim Peter , Burbury Kate , Chapuis Nicolas , Cremers Eline , Della Porta Matteo G. , Dunlop Alan , Eidenschink‐Brodersen Lisa , Font Patricia , Fontenay Michaela , Hobo Willemijn , Ireland Robin , Johansson Ulrika , Loken Michael R. , Ogata Kiyoyuki , Orfao Alberto , Psarra Katherina , Saft Leonie , Subira Dolores , te Marvelde Jeroen , Wells Denise A. , van der Velden Vincent H. J. , Kern Wolfgang , van de Loosdrecht Arjan A.
Published: December 2022

Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow‐up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work‐up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34+CD19−) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work‐up. Looking forward, several machine‐learning‐based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine‐learning‐based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS.
Evaluate your credentials to assess whether skills are useful in the workplace, valuable to students
Authors: Sutton Halley
Published: December 2022

CHICAGO — Can students actually demonstrate the skills they learn from your programs in a way that will better their life outcomes? And do employers understand the competencies students gain when they graduate from your institution? It's a question on the minds of many who work in higher education, and it has an impact for your institution in terms of showing students the value of their degree. The landscape of college credentials is growing, sowing further confusion as each institution often has its own language for discussing similar skills or competencies.
Partitioning variance in immune traits in a zooplankton host—Fungal parasite system
Authors: Westphal Grace H. , Stewart Merrill Tara E.
Published: December 2022

Host immune traits arise from both genetic and environmental sources of variation. When immune traits have a strong genetic basis, the presence and severity of disease in a population may influence the distribution of those traits. Our study addressed how two immune‐related traits (gut penetrability and the hemocyte response) are shaped by genetic and environmental sources of variation, and how the presence of a virulent disease altered the relative frequency of these traits in natural populations. Daphnia dentifera hosts were sampled from five Indiana lakes between June and December 2017 before and during epidemics of their fungal pathogen, Metschnikowia bicuspidata. Collected Daphnia were experimentally exposed to Metschnikowia and assayed for their gut penetrability, hemocyte response, and multi‐locus genotype. Mixed‐effects models were constructed to partition variance in immune traits between genetic and environmental sources. We then isolated the genetic sources to produce genotype‐specific estimates of immune traits for each multi‐locus genotype. Finally, we assessed the relative frequency and dynamics of genotypes during epidemics and asked whether genotypes with more robust immune responses increased in frequency during epidemics. Although genotype was an important source of variation for both gut penetrability and the hemocyte response, environmental factors (e.g., resource availability, Metschnikowia prevalence, and co‐infection) still explained a large portion of observed variation, suggesting a high degree of flexibility in Daphnia immune traits. Additionally, no significant associations were detected between a genotype's immune traits and its frequency in a population. Our study highlights the power of variance partitioning in understanding the factors driving variation in Daphnia traits and motivates further research on immunological flexibility and the ecological drivers of immune variation.
Performance analyses of TAS/Alamouti‐MRC NOMA in dual‐hop full‐duplex AF relaying networks
Authors: Toka Mesut , Güven Eray , Durmaz Mehmet Akif , Karabulut Kurt Güneş , Kucur Oğuz
Published: December 2022

In this article, performance of a multi‐user downlink non‐orthogonal multiple access system in dual‐hop full‐duplex amplify‐and‐forward relaying networks is investigated over Nakagami‐fading channels in the presence of channel estimation error and feedback delay. The base station applies transmit antenna selection (TAS)/Alamouti space‐time block coding scheme, while the users exploit maximum‐ratio combining to utilize benefits of receive diversity. To demonstrate superiority of the proposed system, outage probability (OP) is investigated, and tight lower bound expression is derived to support the exact OP. Moreover, asymptotic analyzes are also conducted for ideal and practical conditions to provide further insights into the OP in high signal‐to‐noise ratio region. In addition, software defined radio based test‐bed implementation is realized to confirm the analysis and show feasibility of the proposed system. Theoretical analyzes verified by simulations and practical implementations demonstrate that more performance improvement can be achieved for the weakest user (with the lowest channel gain) in the case of practical conditions when compared to ideal cases. Also, both diversity order and array gain are dominant in achieving minimum OP (based on relay location) in ideal conditions, while only array gain has effect in practical manner.
Overexpression of UCP4 in astrocytic mitochondria prevents multilevel dysfunctions in a mouse model of Alzheimer's disease
Authors: Rosenberg Nadia , Reva Maria , Binda Francesca , Restivo Leonardo , Depierre Pauline , Puyal Julien , Briquet Marc , Bernardinelli Yann , Rocher Anne‐Bérengère , Markram Henry , Chatton Jean‐Yves
Published: December 2022

Alzheimer's disease (AD) is becoming increasingly prevalent worldwide. It represents one of the greatest medical challenges as no pharmacologic treatments are available to prevent disease progression. Astrocytes play crucial functions within neuronal circuits by providing metabolic and functional support, regulating interstitial solute composition, and modulating synaptic transmission. In addition to these physiological functions, growing evidence points to an essential role of astrocytes in neurodegenerative diseases like AD. Early‐stage AD is associated with hypometabolism and oxidative stress. Contrary to neurons that are vulnerable to oxidative stress, astrocytes are particularly resistant to mitochondrial dysfunction and are therefore more resilient cells. In our study, we leveraged astrocytic mitochondrial uncoupling and examined neuronal function in the 3xTg AD mouse model. We overexpressed the mitochondrial uncoupling protein 4 (UCP4), which has been shown to improve neuronal survival in vitro. We found that this treatment efficiently prevented alterations of hippocampal metabolite levels observed in AD mice, along with hippocampal atrophy and reduction of basal dendrite arborization of subicular neurons. This approach also averted aberrant neuronal excitability observed in AD subicular neurons and preserved episodic‐like memory in AD mice assessed in a spatial recognition task. These findings show that targeting astrocytes and their mitochondria is an effective strategy to prevent the decline of neurons facing AD‐related stress at the early stages of the disease.
Locked In
Authors: Brummett Abram
Published: December 2022

Tiffany was seventeen when injury to her brain stem put her in the intensive care unit on life‐sustaining treatment and in a permanently locked‐in state—fully conscious but able to control no bodily movements other than her eye movements. As a clinical ethicist at the hospital, I was consulted by her neurologist, who had established a blink‐once‐for‐yes, twice‐for‐no system of communication so that Tiffany could respond to questions. Her mother wanted Tiffany to continue receiving treatment that could prolong her life for years, potentially decades. In a meeting with the neurologist and family, I felt like suggesting what nobody seemed willing to suggest: that we should ask Tiffany what she wants.
Investigating cognitive neuroscience theories of human intelligence: A connectome‐based predictive modeling approach
Authors: Anderson Evan D. , Barbey Aron K.
Published: December 2022

Central to modern neuroscientific theories of human intelligence is the notion that general intelligence depends on a primary brain region or network, engaging spatially localized (rather than global) neural representations. Recent findings in network neuroscience, however, challenge this assumption, providing evidence that general intelligence may depend on system‐wide network mechanisms, suggesting that local representations are necessary but not sufficient to account for the neural architecture of human intelligence. Despite the importance of this key theoretical distinction, prior research has not systematically investigated the role of local versus global neural representations in predicting general intelligence. We conducted a large‐scale connectome‐based predictive modeling study (N = 297), administering resting‐state fMRI and a comprehensive cognitive battery to evaluate the efficacy of modern neuroscientific theories of human intelligence, including spatially localized theories (Lateral Prefrontal Cortex Theory, Parieto‐Frontal Integration Theory, and Multiple Demand Theory) and recent global accounts (Process Overlap Theory and Network Neuroscience Theory). The results of our study demonstrate that general intelligence can be predicted by local functional connectivity profiles but is most robustly explained by global profiles of whole‐brain connectivity. Our findings further suggest that the improved efficacy of global theories is not reducible to a greater strength or number of connections, but instead results from considering both strong and weak connections that provide the basis for intelligence (as predicted by the Network Neuroscience Theory). Our results highlight the importance of considering local neural representations in the context of a global information‐processing architecture, suggesting future directions for theory‐driven research on system‐wide network mechanisms underlying general intelligence.
Do good carefully: The long‐term effects of low‐dose DDT exposure in early childhood on education, marriage and employment
Authors: Chang Simon , Kan Kamhon
Published: December 2022

It is well known that malaria has serious adverse effects on humans. Yet, little is known as to how dichlorodiphenyltrichloroethane (DDT), which is still used to control malaria, may affect human socioeconomic outcomes in the long run. Utilizing the large‐scale indoor residual spraying of low‐dose DDT in Taiwan in the 1950s, we estimated the long‐term effects of low‐dose DDT exposure in early childhood on education, marriage and employment in adulthood. Our identification hinges on the unexpected extension of DDT spraying after malaria had already been largely brought under control. We found that even at a very low dosage, DDT exposure still resulted in discernible negative effects on education and marriage. For employment, although no effect on the probability of working was detected, people exposed to more sprayings in childhood were more likely to work in the agricultural sector that typically requires less human capital.
Correcting Hargreaves‐Samani formula using geographical coordinates and rainfall over different timescales
Authors: Elagib Nadir Ahmed , Musa Ammar Ahmed
Published: December 2022

The United Nations Food and Agricultural Organization (FAO) approved the Hargreaves‐Samani formula (HAR‐85) as an alternative to the standard Penman‐Monteith method (FAO‐PM) for estimating grass reference evapotranspiration (ETo). With much less data demand, HAR‐85 is unequivocally useful where meteorological variables are often scarce, incomplete or unavailable. Herein, we evaluate HAR‐85 against FAO‐PM across 2.505 million km2, representing Sudan and South Sudan and encompassing wide hydroclimate domains including the Nile River. We further propose simple year‐round and seasonal adjustment models to correcting HAR‐85 across the entire study area. The models express HAR‐85's error in multiple linear regressions in terms of latitude, longitude, altitude and/or monthly rainfall. Varying data periods, including odd, even and all years, are used in the evaluation and the adjustment models development and validation processes to investigate the influence of changing data period. A suit of eight performance indicators shows dependency of the original bias of HAR‐85 on the geographical location, monthly rainfall amount, season of the year and data period. All error indicators amplify southward from the hyper‐arid region to the dry sub‐humid zone. For example, the mean bias error (MBE) ranges from −0.51 to 1.29 mm/day, respectively. Study area‐wide, HAR‐85 least represents FAO‐PM during the hottest month and the transitional month (between the wet and dry‐cool seasons) with MBE of 0.65 and 0.70 mm/day, respectively. Conversely, it represents FAO‐PM the most in the wettest month, with smallest MBE of 0.32 mm/day. Beholding this spatiotemporal trait, the final yearly and seasonal adjustment models developed herein enormously moderate the predominant overestimation of the original HAR‐85. The former model explains 46.7% of the error variance whereas 36.9% to 62.3% of the variation in the error is explainable by the latter models. These adjustment models narrow the monthly MBE among the stations from −0.71‐2.17 to −0.80‐1.20 and −0.65‐0.99 mm/day, respectively. Without undermining the accuracy, the year‐round adjustment model can still be feasibly recommended for general use across the study area.
A case of acute lymphocytic gastritis related to treatment with pembrolizumab for metastatic urothelial carcinoma
Authors: Fukiishi Yousuke , Fukuhara Hideo , Kurano Yoshitaka , Shugimoto Hiroki , Yamashita Erika , Karasima Takashi , Inoue Keiji
Published: December 2022

Introduction

Immune checkpoint inhibitors such as programmed cell death/−ligand 1 inhibitor and cytotoxic T‐lymphocyte‐associated antigen‐4 inhibitors have been widely used for various advanced malignancies. The mechanism of action for these inhibitors is the improvement of antitumor immunity via T‐cell modulation. On the contrary, immune‐related adverse events such as autoimmune colitis might arise in association with T‐cell activation. Upper gastrointestinal adverse events related to pembrolizumab have rarely been reported.

Case presentation

A 72‐year‐old man underwent laparoscopic radical cystectomy for muscle‐invasive bladder cancer (pT2N0M0). Multiple lymph node metastases appeared in the paraaortic region. First‐line chemotherapy comprising gemcitabine and carboplatin failed to stop disease progression. After the administration of pembrolizumab as second‐line treatment, the patient showed symptomatic gastroesophageal reflux disease. Esophagogastroduodenoscopic biopsy of the gastric body showed severe lymphoplasmacytic and neutrophilic infiltration.

Conclusion

We present acute gastritis related to pembrolizumab. Early eradication therapy may be able to control immune checkpoint inhibitor‐related gastritis.
Deciphering mechanistic implications of antimicrobial and antioxidant potentials of certain new dibutyltin(IV) formulations as possible therapeutic options based on DFT and hybrid materials paradigm
Authors: Soni Komal , Saxena Sanjiv , Jain Asha
Published: December 2022

Mechanistic implications of antimicrobial and in vitro antioxidant potentials of a set of newly generated nonbridged mononuclear N,O‐orthometallated and carboxylate bridged binuclear nonorthometallated dibutyltin(IV) formulations have been investigated. Some of these formulations were screened for their antibacterial and antifungal activities against Escherichia coli and Candida albicans, respectively whereas in vitro antioxidant potential was examined by Ferric reducing antioxidant power (FRAP) assay. Nonbridged mononuclear N,O‐orthometallated dibutyltin(IV) formulations were generated by the reactions of Bu2SnCl2 with sodium salts of 2‐aminophenol/substituted 2‐aminophenol and flexible N‐protected amino acids in 1:1:1 molar ratio in refluxing dry THF. Plausible structures of these nonbridged mononuclear N,O‐orthometallated dibutyltin(IV) formulations containing flexible N‐protected amino acids have been suggested on the basis of spectroscopic and mass studies of some representative formulations. Plausible structures suggested on the basis of spectroscopic studies are corroborated by density functional theory (DFT/B3LYP method) (SPARTAN‐20) investigation of a representative dibutyltin(IV) complex and the ligands involved in it. The presence of two different classes of organic ligands in this complex provides an opportunity to study optimized topologies, bonding, distortions, optimized energy, and stability of the complex.
Proteomics analysis of meclofenamic acid‐treated small cell lung carcinoma cells revealed changes in cellular energy metabolism for cancer cell survival
Authors: Yanar Sevinc , Kasap Murat , Kanli Aylin , Akpinar Gurler , Sarihan Mehmet
Published: December 2022

Small cell lung carcinoma (SCLC) is a highly aggressive cancer with low survival rate. Although initial response to chemotherapy in SCLC patients is well‐rated, the treatments applied after the disease relapses are not successful. Drug resistance is accepted to be one of the main reasons for this failure. Therefore, there is an urgent need for new treatment strategies for SCLC. Meclofenamic acid, a nonsteroidal anti‐inflammatory drug, has been shown to have anticancer effects on various types of cancers via different mechanisms. The aim of this study was to investigate the alterations that meclofenamic acid caused on a SCLC cell line, DMS114 using the tools of proteomics namely two‐dimensional gel electrophoresis coupled to MALDI‐TOF/TOF and nHPLC coupled to LC‐MS/MS. Among the proteins identified by both methods, those showing significantly altered expression levels were evaluated using bioinformatics databases, PANTHER and STRING. The key altered metabolism upon meclofenamic acid treatment appeared to the cellular energy metabolism. Glycolysis was suppressed, whereas mitochondrial activity and oxidative phosphorylation were boosted. The cells underwent metabolic reprogramming to adapt into their new environment for survival. Metabolic reprogramming is known to cause drug resistance in several cancer types including SCLC. The identified differentially regulated proteins in here associated with energy metabolism hold value as the potential targets to overcome drug resistance in SCLC treatment.
IGF2BP2 enhances LincRNA01116 stability via m6A: A potential biomarker and therapeutic target for patients with pre‐eclampsia
Authors: Zhang Tingting , Tang Xiaotong , Zhu Yuanyuan , Wang Cong , Jiang Ziyan , Yang Nana , Wang Tianjun , Shu Lijun , Xu Yetao , Sun Lizhou
Published: December 2022

Pre‐eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR‐210‐3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.
Effect of non‐covalent interactions in 2,5‐di‐Me‐pyrazine‐di‐N‐oxide ‐ methanol – Carbon nanotube electrocatalytic system
Authors: Kulakovskaya Svetlana I. , Zyubina Tatyana S. , Zyubin Alexander S. , Kulikov Alexander V. , Ryabenko Alexander G. , Zolotukhina Ekaterina V. , Dobrovolskiy Yuriy A.
Published: December 2022

Catalytic oxidation of methanol (MeOH) in the absence of noble metals and noble metal oxides as catalysts, and the use of metal‐free materials are inexpensive and attractive process for practical use in electrocatalysis, sensors, and in direct methanol fuel cells. In previous works, it was found that the use of single‐walled (SWCNT) or multi‐walled (MWCNT) carbon nanotube paper electrodes instead of GC increases the catalytic efficiency of organic compounds oxidation in the presence of aromatic di‐N‐oxides by several times. In this work, the effect of non‐covalent interactions on the catalytic efficiency of MeOH oxidation in the presence of 2,5‐di‐Me‐pyrazine‐di‐N‐oxide (Pyr1) in 0.1 M Bu4NClO4 solution in acetonitrile at SWCNT and MWСNT paper electrodes was studied by the methods of quantum chemical modeling, Raman spectroscopy, and using electrochemical data. New factors determined the features of mechanism of MeOH oxidation on CNT electrodes and lead to an increase in the catalytic efficiency of the electrode process in comparison with the GC electrode were established.
The AP2/ERF transcription factor ORA59 regulates ethylene‐induced phytoalexin synthesis through modulation of an acyltransferase gene expression
Authors: Huang Li‐Jun , Zhang Jiayi , Lin Zeng , Yu Peiyao , Lu Mengzhu , Li Ning
Published: December 2022

The gaseous ethylene (ET) and the oxylipin‐derived jasmonic acid (JA) in plants jointly regulate an arsenal of pathogen responsive genes involved in defending against necrotrophic pathogens. The APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factor ORA59 is a major positive regulator of the ET/JA‐mediated defense pathway in Arabidopsis thaliana. The Arabidopsis agmatine coumaroyltransferase (AtACT) catalyzes the formation of hydroxycinnamic acid amides (HCAAs) which are effective toxic antimicrobial substances known as phytoalexins and play an important role in plant defense response. However, induction and regulation of AtACT gene expression and HCAAs synthesis in plants remain less understood. Through gene coexpression network analysis, we identified a list of GCC‐box cis‐element containing genes that were coexpressed with ORA59 under diverse biotic stress conditions and might be potential downstream targets of this AP2/ERF‐domain transcription factor. Particularly, ORA59 directly binds to AtACT gene promoter via the GCC‐boxes and activates AtACT gene expression. The ET precursor 1‐aminocyclopropane‐1‐carboxylic acid (ACC)‐treatment significantly induces AtACT gene expression. Both ORA59 and members of the class II TGA transcription factors are indispensable for ACC‐induced AtACT expression. Interestingly, the expression of AtACT is also subject to the signaling crosstalk of the salicylic acid‐ and ET/JA‐mediated defense response pathways. In addition, we found that genes of the phenylpropanoid metabolism pathway were specifically induced by Botrytis cinerea. Taking together, these evidence suggest that the ET/JA signaling pathway activate the expression of AtACT to increase antimicrobial HCAAs production through the transcription factor ORA59 in response to the infection of necrotrophic plant pathogens.
The role and mechanism of long non‐coding RNAs in homologous recombination repair of radiation‐induced DNA damage
Authors: Yu Nanxi , Qin Hongran , Zhang Fangxiao , Liu Tingting , Cao Kun , Yang Yanyong , Chen Yuanyuan , Cai Jianming
Published: December 2022

DNA double‐strand breaks can seriously damage the genetic information that organisms depend on for survival and reproduction. Therefore, cells require a robust DNA damage response mechanism to repair the damaged DNA. Homologous recombination (HR) allows error‐free repair, which is key to maintaining genomic integrity. Long non‐coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides. In recent years, a number of studies have found that lncRNAs can act as regulators of gene expression and DNA damage response mechanisms, including HR repair. Moreover, they have significant effects on the occurrence, development, invasion and metastasis of tumor cells, as well as the sensitivity of tumors to radiotherapy and chemotherapy. These studies have therefore begun to expose the great potential of lncRNAs for clinical applications. In this review, we focus on the regulatory roles of lncRNAs in HR repair.
A phase III, randomised, double‐blind, multi‐national clinical trial comparing SB12 (proposed eculizumab biosimilar) and reference eculizumab in patients with paroxysmal nocturnal haemoglobinuria
Authors: Jang Jun Ho , Gomez Roberta Demichelis , Bumbea Horia , Nogaieva Larysa , Wong Lily Lee Lee , Lim Soo Min , Kim Younsoo , Park Jihye
Published: December 2022

Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double‐blind, multi‐national cross‐over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12‐ECU or ECU‐SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross‐over at week 26). Primary endpoints were LDH at week 26 and the time‐adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] −47·66‒116·62 U/l) and geometric LSM ratio of time‐adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre‐defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti‐drug antibodies. Treatment‐emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12‐use in PNH patients.
Sexually dimorphic characters of the ultimate legs in lithobiid centipedes (Myriapoda, Chilopoda, and Lithobiomorpha): Morphology and implications for reproductive behavior
Authors: Roithmair Zita , Edgecombe Gregory D. , Wanninger Andreas , Akkari Nesrine
Published: December 2022

Many species of lithobiomorph centipedes present a pronounced sexual dimorphism reflected in remarkable structural modifications on the ultimate legs of males. Most records of these male secondary sexual characters addressed taxonomy, helping to identify and characterize species or diagnose genera, but information on their diversity, detailed morphology and possible function(s) is scarce. In this study, nine species of the two lithobiid genera Lithobius Leach, 1814 and Eupolybothrus Verhoeff, 1907 were investigated, using light and scanning electron microscopy to document the detailed morphology of secondary sexual characters of male ultimate legs. Secondary sexual characters affecting the cuticle of the ultimate legs are described in detail and found to often be associated with sensilla, interpreted here as chemo‐ and mechanoreceptors, and with clusters of pores, a hitherto undescribed pore‐distribution for this group. The tibial nodule of the species Lithobius nodulipes Latzel, 1880, was additionally examined with histological semi‐thin sections. These results revealed that the clustered pores are connected to glandular tissue, and are, based on their morphology, interpreted as openings of flexo‐canal epidermal glands. The presence of various sensory and glandular structures associated with sexual dimorphism indicates a likely role during courtship and mating. The closely related species examined in this research show comparable dimorphic structures, which are otherwise species‐specific. Morphological observations on secondary sexual structures inform on reproductive biology in groups like lithobiomorphs for which there are limited behavioral data.
Chemical profiling and identification of Radix Cudramiae and their metabolites in rats using an ultra‐high‐performance liquid chromatography method coupled with time‐of‐flight tandem mass spectrometry
Authors: Liu Qing , Pei Yuqiong , Wan Haoting , Wang Mengqing , Liu Luyao , Li Weidong , Jin Junjie , Liu Xiao
Published: December 2022

Radix Cudramiae, known as “Chuan‐Po‐Shi” in China, is a herbal medicine widely used in the southwest of the country, especially applied by the Miao and Zhuang nationalities for the treatment of liver diseases, such as acute liver injury and liver fibrosis. As a kind of ethnomedicine, the report on its chemical analysis was still blank, which restricted its clinical application. Therefore, this paper aimed to illustrate the chemical characteristics of Radix Cudramiae. A rapid analytical strategy based on ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry was developed to profile the natural small‐molecular compounds in Radix Cudramiae, as well as the related prototypes and their metabolites in rats after drug administration. As a result, a total of 74 compounds were detected in the aqueous exact of Radix Cudramiae. In vivo, 45 chemicals including 16 prototypes and 29 metabolites in rat serum, along with 35 chemicals including 17 prototypes and 18 metabolites in rat liver, were screened out and identified. For the first time, the chemical constituents of Radix Cudramiae and their metabolic characteristics were discovered. It was hoped that this work would be beneficial for the safe and effective application of Radix Cudramiae in a clinic.
Total Thyroidectomy and Subsequent Weight Gain in Pediatric Populations
Authors: Edwards Evan R. , Hazkani Inbal , Stein Eli , Josefson Jami L. , Samis Jill H. , Miller Jennifer L. , Rastatter Jeffrey
Published: December 2022

Objective

To evaluate weight gain in children post‐thyroidectomy and identify predictors.

Methods

Charts from patients at a tertiary health care facility who underwent total thyroidectomy from 2014 to 2020 were reviewed for Body Mass Index z‐scores (BMIz) at the time of thyroidectomy and at 1 and 2‐year post‐operation intervals. Patient demographic information, comorbidities, pre‐ and postoperative thyroid stimulating hormone, and postoperative free T4 levels were also extracted. Patients with other known endocrine abnormalities, chronic kidney disease, or without sufficient follow‐up were excluded.

Results

A total of 56 patients (ages 3–17 years old) met the inclusion criteria (n = 17 Graves' disease; n = 39 presumed cancer). Over the first year, average BMIz significantly increased in patients with Graves' disease (∆BMIz = 0.45 ± 0.77, p = 0.03), Hispanic ethnicity (∆BMIz = 0.43 ± 0.68, p = 0.004), Medicaid/no insurance coverage (∆BMIz = 0.33 ± 0.74, p = 0.038), age <13 years at thyroidectomy (∆BMIz = 0.35 ± 0.68, p = 0.016), and persistent postoperative hypothyroidism (∆BMIz = 0.41 ± 0.41, p = 0.012). These changes remained significant after the second year. Age at thyroidectomy correlated negatively with ∆BMIz only after the first year (r = −0.40, p = 0.002). Regression analysis, controlling for Graves' status, persistent postoperative hypothyroidism, and insurance coverage, identified age at thyroidectomy as a significant predictor of ∆BMIz after the first year (b = −0.06, p = 0.004) and Hispanic ethnicity as a significant predictor after the second year (b = 0.60, p = 0.003).

Conclusion

A small increase in BMIz post‐thyroidectomy was observed across several patient subgroups. Younger age at thyroidectomy and Hispanic ethnicity were associated with increased BMIz in the first 2 years post‐thyroidectomy.

Level of Evidence

Level 4 ‐ Historically controlled cohort Laryngoscope, 133:1518–1523, 2023
Effect of drying on kinetics, physiochemical, and antioxidant properties of black gram nuggets
Authors: Nahar Najmun , Raychaudhuri Utpal , Adhikari (Nee Pramanik) Sunita
Published: December 2022

Black gram (Vigna mungo) nuggets are locally known as “bori” and are an indigenous food and are consumed widely in the Indian subcontinent. The objective of the work was to compare the mode of selected drying techniques (hot‐air, freeze, and microwave drying) on drying kinetics followed by the development of suitable mathematical modeling for the process. Additionally, the antioxidant, color, and textural properties of the dried nuggets were evaluated for their acceptability and associated health benefits. Based on regression parameters, it was found that the Page model fitted well (R2 = 0.99) with the experimental data when compared with other models. The effective moisture diffusivity exhibited an inverse relation to drying time. Among tested drying techniques, it was found that TB in microwave drying at 450 W had the highest amount of phenolic content (5.27 mg/g), flavonoid content (1.72 mg/100 g), ferric reducing antioxidant power assay (45.71 μmol/g), 61.42 μmol/g of ABTS assay, and 67.81 μmol/g of DPPH assay values. The freeze‐drying products were better for physicochemical parameters than other drying process products. The presence of phytochemicals was responsible for the high bioactivity of microwave‐dried nuggets.
PLIC11 drives lung cancer progression through regulating the YY1/PIWIL4 axis
Authors: Zhu Yuyao , Chen Bing , Pan Hongyu , Sun Lei , Yu Tao
Published: December 2022

Lung cancer is the leading cause of cancer related deaths worldwide. Nonsmall cell lung cancers (NSCLC), the most common histological type of lung cancer, are known to be less well characterized. Long noncoding RNAs are a new class of cancer regulators. Here, we aimed to investigate the effect of lncRNA PLIC11 in NSCLC progression. In our study, we found that PLIC11 was upregulated in lung cancer, particularly in metastatic lung cancer tissues. Overexpression of PLIC11 enhanced cell proliferation, migration, and metastasis in vitro and in vivo. Mechanically, PLIC11 could interact with YY1 and promote PIWIL4 expression by transcription activation. Therefore, PLIC11 upregulation is a potential indicator of aggressive lung cancer, Silencing of PLIC11 has great potential therapeutic strategy in NSCLC.
Opposing effects of trans‐ and cis‐cinnamic acid during rice coleoptile elongation
Authors: Vlaminck Lena , De Rouck Brix , Desmet Sandrien , Van Gerrewey Thijs , Goeminne Geert , De Smet Lien , Storme Veronique , Kyndt Tina , Demeestere Kristof , Gheysen Godelieve , Inzé Dirk , Vanholme Bartel , Depuydt Stephen
Published: December 2022

The phenylpropanoid cinnamic acid (CA) is a plant metabolite that can occur under a trans‐ or cis‐form. In contrast to the proven bioactivity of the cis‐form (c‐CA), the activity of trans‐CA (t‐CA) is still a matter of debate. We tested both compounds using a submerged rice coleoptile assay and demonstrated that they have opposite effects on cell elongation. Notably, in the tip of rice coleoptile t‐CA showed an inhibiting and c‐CA a stimulating activity. By combining transcriptomics and (untargeted) metabolomics with activity assays and genetic and pharmacological experiments, we aimed to explain the underlying mechanistic processes. We propose a model in which c‐CA treatment activates proton pumps and stimulates acidification of the apoplast, which in turn leads to the loosening of the cell wall, necessary for elongation. We hypothesize that c‐CA also inactivates auxin efflux transporters, which might cause a local auxin accumulation in the tip of the coleoptile. For t‐CA, the phenotype can partially be explained by a stimulation of cell wall polysaccharide feruloylation, leading to a more rigid cell wall. Metabolite profiling also demonstrated that salicylic acid (SA) derivatives are increased upon t‐CA treatment. As SA is a known antagonist of auxin, the shift in SA homeostasis provides an additional explanation of the observed t‐CA‐mediated restriction on cell growth.
Theoretical Conditions for Burning in Solid Propellant Slots
Authors: Hafner Thomas A. , Örnek Metin , Messer Derek K. , Son Steven F.
Published: December 2022

Solid propellants suffer from a lack of active burning rate control. Active control could be capable of throttling propellant gas generation rates in applications ranging from adaptable airbags or other gas generators to solid rocket motors. In this study, we have investigated the concept of altering the burning behavior of solid propellants via surface area modification in the form of an adjacent slot. The conditions for burning in an adjacent slot to occur are considered, and several theoretical relationships are developed and presented between pressure and slot width for the threshold condition for penetration. The derivations assumed several different threshold criteria. Most considered convective heat transfer and applied an ignition threshold, whereas one derivation examined the quenching of a flame propagating into a slot. The resulting expressions were then applied to existing literature data and contrasted. The results showed that the derived equations fit the literature data well with our equation from the flame quenching derivation having the highest average R squared value.
An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup
Authors: Diezi Léonore , Dao Kim , Jullien Vincent , Roussel‐Maupetit Caroline , Burton Ingrid , André Pascal , Bardinet Carine , Rothuizen Laura E. , Chtioui Haithem , Manso‐Silvan Maria A. , Guittet Catherine , Brunner‐Ferber Françoise , Vandenhende Francois , Chiron Catherine , Granier Luc‐André , Buclin Thierry
Published: December 2022

Ethosuximide, the first‐line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar‐free, tasteless formulation convenient for pediatric use. This dual Phase‐I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo‐controlled, partly blinded, 3‐way cross‐over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose‐normalized Cmax and AUC0–∞ was 93.7% [90% CI: 76.3–115.1] and 96.1% [91.0–101.5], respectively. For granules B it was 87.6% [81.6–94.0] and 92.5% [88.5–96.6], respectively, with slightly delayed tmax of 0.75 h [0.5–4.05] compared to syrup 0.5 h [0.3–0.8]. Tolerability visual analog scales revealed a trend for statistically non‐significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar‐free, tasteless, bioequivalent, and well‐tolerated while enabling precise adjustment to body weight.