bluuebunny/crossref_metadata_2025 huggingface dataset:
Securitisation of Ukrainian Critical Infrastructures: The Case of the Failure of SCADA System in Protecting the Power Grids
Authors: Nurfarah Nidatya, Muhammad Kamil Ghiffary Abdurrahman Dini Putri Saraswati,
Published: January 2023

Critical infrastructures are the important element to support the social cohesion in a certain area. Therefore, it is necessary to protect critical infrastructures in order to maintain the sustainability of the assets. There are many attempts of states to control the security of their critical infrastructures, one of them is using Supervisory Control and Data Acquisition (SCADA) system, a control system in which to monitor and retrieve data under the supervision of an operator. However, although countries are aware of the preventive action over their critical infrastructures, it is still possible to fail. In this case, Ukraine which has a relatively secure control system was failed in protecting its power grids from multiple hacker attacks which contributed to blackouts in December 2015. The devastating failure of Ukraine’s security system has led public opinion to point a finger to Russia since the relationship of both countries is at stake. In this sense, Ukraine issued a speech act to securitise its critical infrastructures. By exercising securitisation theory, this article would discuss further about the fruitfulness of the speech act after the failure of the security system in protecting Ukraine’s power grids.
China Digital Silk Road And Indonesia Digital Transformation
Authors: Radita Gora Tayibnapis Muhammad Abdurrohim,
Published: January 2023

The Belt and Road Initiative (BRI), the signature project of the Xi Jinping regime, has established a wide range of lofty goals that would usher in a new chapter of China's integration into the global market system and expand Chinese influence. Notably, China's now-powerful digital companies and cyberspace power actively sought a significant position in this massive statist effort under the policy banner of establishing a Digital Silk Road. Under this project, Beijing has multiple policy mechanisms to spread its digital power. Indonesia's enormous digital economy potential has become a significant target of this project. Using the qualitative method and analyzing two-level games by Robert D Putnam, this research will explain the relationship of Indonesian domestic actors concerning China's digital silk road. This research argues that the digital silk road in Indonesia has made more progress than other BRI projects because the DSR has integrated with the government, private sectors, and parliament's need for digital transformation. When the approval rating of domestic stakeholders is high, the success of the cooperation will be high too.
Indonesia’s Presidency On G20 2022: Unpacking Its Digital Economic Diplomacy In Advancing Indonesian MSMES Digital Economic Transformation
Authors: Chantika Salsabila Alarsah, Andi Faradilla Ayu Lestari Abdul Razaq Cangara, Bama Andika Putra, Patrice Lumumba,,
Published: January 2023

After a long period of membership in the Premier global forum of G20, Indonesia has taken the lead in the G20 Presidency 2022. With a theme of "Recover Together, Recover Stronger" to encounter the multi-spectrum repercussion of the Covid-19 Pandemic, Indonesia set out three main agendas of deliberation within, encompassing Global Health Architecture (GHA), Digital Economic Transformation (DET) and Energy Transition (ET). This article considers and puts forward the DET agenda, particularly the Micro, Small, and Medium Enterprises (MSMEs) DET, as the main discussion in this article. It assumes DET agenda that could significantly encounter the problem of economic downturn with its following consequences of losses of many jobs and rising unemployment. Therefore, this article scrutinizes how Indonesia's G20 Presidency could elevate its economic diplomacy capacity to achieve its MSMEs' DET interests. For this purpose, this article employs the analytical framework tailored from the integrated perspective of economic diplomacy, digital economy, and digital economic transformation. This article argues that Indonesia's G20 Presidency has advantaged Indonesia by giving more policy and diplomatic room to campaign and mainstream its MSMEs DET interests to multiple stakeholders from all G20 countries. It consequently crystallizes MSMEs DET as both a normative and practical agenda globally in which Indonesia could further entertain its MSMEs DET interest. In such ways, it is expected that Indonesia could recover its economy after the pandemic, particularly with the advancement of its MSME economic environment. This argument is based on the mapping of the G20 events dynamic substantiating MSMEs DET from December to October 2022. Overall, despite Indonesia's MSMEs DET interest achievement in G20 2022, Indonesia still needs to strengthen its economic diplomacy endeavour related to MSMEs DET in the following G20s forums.
Cardiometabolic risk factors among children and adolescents with overweight and Class 1 obesity: A cross-sectional study. Insights from stratification of Class 1 obesity
Authors: Nakhleh Afif , Sakhnini Rizan , Furman Eyal , Shehadeh Naim
Published: January 2023

Context

Severe childhood obesity is associated with increased prevalence of cardiometabolic risk factors (CMRFs). Among children with Class 1 obesity, higher BMI may indicate greater cardiometabolic risk. Class 1 obesity reflects a wide spectrum of BMI values. Each 10% increase in BMI above the 95th percentile is equivalent to an average increase of 2.15 kg/m2 and 2.75 kg/m2 in BMI among children and adolescents, respectively. Such increments may be of clinical importance.

Objectives

The study aimed to determine the prevalence and clustering of CMRFs in children and adolescents with BMI 110%-119% of the 95th BMI percentile.

Methods

A cross-sectional analysis of data, from an Israeli health maintenance organization, of children and adolescents (5-17 years) with overweight or Class 1 obesity, and at least one measurement of lipid profile during Jan/2020-May/2021. CMRFs were defined as abnormal lipid profile, elevated alanine aminotransferase, hypertension, and prediabetes or diabetes. Study groups included overweight and Class 1 Obesity-A (BMI < 110%) and Obesity-B (BMI ≥ 110%) of the 95th BMI percentile.

Results

Of 7211 subjects included, 40.2% were overweight, 50.3% obesity-A, and 9.5% obesity-B. Multivariable analyses showed that children and adolescents from the Obesity-B group had increased odds for higher triglycerides, LDL cholesterol, and ALT levels; and lower HDL cholesterol levels, as compared to Obesity-A. The odds of prediabetes (insignificant) tended to be higher in the Obesity-B group, which was associated with increased CMRFs clustering.

Conclusions

Among children and adolescents with Class 1 obesity, BMI ≥ 110% of the 95th percentile was associated with higher prevalence and clustering of CMRFs.
Spectrum of germline and somatic mitochondrial DNA variants in Tuberous Sclerosis Complex
Authors: Giannikou Krinio , Martin Katie R. , Abdel-Azim Ahmad G. , Pamir Kaila J. , Hougard Thomas R. , Bagwe Shefali , Tang Yan , MacKeigan Jeffrey P. , Kwiatkowski David J. , Henske Elizabeth P. , Lam Hilaire C.
Published: January 2023

Tuberous Sclerosis Complex (TSC) is caused by loss of function variants in either TSC1 or TSC2 and is characterized by broad phenotypic heterogeneity. Currently, there is limited knowledge regarding the role of the mitochondrial genome (mtDNA) in TSC pathogenesis. In this study, we aimed to determine the prevalence and spectrum of germline and somatic mtDNA variants in TSC and identify potential disease modifiers. Analysis of mtDNA amplicon massively parallel sequencing (aMPS) data, off-target mtDNA from whole-exome sequencing (WES), and/or qPCR, revealed mtDNA alterations in 270 diverse tissues (139 TSC-associated tumors and 131 normal tissue samples) from 199 patients and six healthy individuals. Correlation of clinical features to mtDNA variants and haplogroup analysis was done in 102 buccal swabs (age: 20–71 years). No correlation was found between clinical features and either mtDNA variants or haplogroups. No pathogenic variants were identified in the buccal swab samples. Using in silico analysis, we identified three predicted pathogenic variants in tumor samples: MT-ND4 (m.11742G>A, p. Cys328Tyr, VAF: 43%, kidney angiomyolipoma), MT-CYB (m.14775T>C, p. Leu10Pro, VAF: 43%, LAM abdominal tumor) and MT-CYB (m.15555C>T, p. Pro270Leu, VAF: 7%, renal cell carcinoma). Large deletions of the mitochondrial genome were not detected. Analysis of tumors from 23 patients with corresponding normal tissue did not reveal any recurrent tumor-associated somatic variants. The mtDNA/gDNA ratio between tumors and corresponding normal tissue was also unchanged. Overall, our findings demonstrate that the mitochondrial genome is highly stable across tissues and within TSC-associated tumors.
Reprogramming of IL-12 secretion in the PDCD1 locus improves the anti-tumor activity of NY-ESO-1 TCR-T cells
Authors: Kim Segi , Park Cho I , Lee Sunhwa , Choi Hyeong Ryeol , Kim Chan Hyuk
Published: January 2023

Introduction

Although the engineering of T cells to co-express immunostimulatory cytokines has been shown to enhance the therapeutic efficacy of adoptive T cell therapy, the uncontrolled systemic release of potent cytokines can lead to severe adverse effects. To address this, we site-specifically inserted the interleukin-12 (IL-12) gene into the PDCD1 locus in T cells using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based genome editing to achieve T-cell activation-dependent expression of IL-12 while ablating the expression of inhibitory PD-1.

Methods

New York esophageal squamous cell carcinoma 1(NY-ESO-1)-specific TCR-T cells was investigated as a model system. We generated ΔPD-1-IL-12 -edited NY-ESO-1 TCR-T cells by sequential lentiviral transduction and CRISPR knock-in into activated human primary T cells.

Results

We showed that the endogenous PDCD1 regulatory elements can tightly control the secretion of recombinant IL-12 in a target cell-dependent manner, at an expression level that is more moderate than that obtained using a synthetic NFAT-responsive promoter. The inducible expression of IL-12 from the PDCD1 locus was sufficient to enhance the effector function of NY-ESO-1 TCR-T cells, as determined by upregulation of effector molecules, increased cytotoxic activity, and enhanced expansion upon repeated antigen stimulation in vitro. Mouse xenograft studies also revealed that PD-1-edited IL-12-secreting NY-ESO-1 TCR-T cells could eliminate established tumors and showed significantly greater in vivo expansion capacity than control TCR-T cells.

Discussion

Our approach may provide a way to safely harness the therapeutic potential of potent immunostimulatory cytokines for the development of effective adoptive T cell therapies against solid tumors.
Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature
Authors: Duijster Janneke W. , Lieber Thomas , Pacelli Silvia , Van Balveren Leontine , Ruijs Loes S. , Raethke Monika , Kant Agnes , Van Hunsel Florence
Published: January 2023

Background

Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature.

Methods

Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of ‘any AEFI’, local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination.

Results

The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females.

Discussion

The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.
Interferon alpha inducible protein 6 is a negative regulator of innate immune responses by modulating RIG-I activation
Authors: Villamayor Laura , Rivero Vanessa , López-García Darío , Topham David J. , Martínez-Sobrido Luis , Nogales Aitor , DeDiego Marta L.
Published: January 2023

Interferons (IFNs), IFN-stimulated genes (ISGs), and inflammatory cytokines mediate innate immune responses, and are essential to establish an antiviral response. Within the innate immune responses, retinoic acid-inducible gene I (RIG-I) is a key sensor of virus infections, mediating the transcriptional induction of IFNs and inflammatory proteins. Nevertheless, since excessive responses could be detrimental to the host, these responses need to be tightly regulated. In this work, we describe, for the first time, how knocking-down or knocking-out the expression of IFN alpha-inducible protein 6 (IFI6) increases IFN, ISG, and pro-inflammatory cytokine expression after the infections with Influenza A Virus (IAV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and Sendai Virus (SeV), or poly(I:C) transfection. We also show how overexpression of IFI6 produces the opposite effect, in vitro and in vivo, indicating that IFI6 negatively modulates the induction of innate immune responses. Knocking-out or knocking-down the expression of IFI6 diminishes the production of infectious IAV and SARS-CoV-2, most likely because of its effect on antiviral responses. Importantly, we report a novel interaction of IFI6 with RIG-I, most likely mediated through binding to RNA, that affects RIG-I activation, providing a molecular mechanism for the effect of IFI6 on negatively regulating innate immunity. Remarkably, these new functions of IFI6 could be targeted to treat diseases associated with an exacerbated induction of innate immune responses and to combat viral infections, such as IAV and SARS-CoV-2.
Correlation of microbiomes in “plant-insect-soil” ecosystem
Authors: Li Guomeng , Liu Peng , Zhao Jihan , Su Liangyinan , Zhao Mengyu , Jiang Zhengjie , Zhao Yang , Yang Xiping
Published: January 2023

Introduction

Traditional chemical control methods pose a damaging effect on farmland ecology, and their long-term use has led to the development of pest resistance.

Methods

Here, we analyzed the correlations and differences in the microbiome present in the plant and soil of sugarcane cultivars exhibiting different insect resistance to investigate the role played by microbiome in crop insect resistance. We evaluated the microbiome of stems, topsoil, rhizosphere soil, and striped borers obtained from infested stems, as well as soil chemical parameters.

Results and Discussion

Results showed that microbiome diversity was higher in stems of insect-resistant plants, and contrast, lower in the soil of resistant plants, with fungi being more pronounced than bacteria. The microbiome in plant stems was almost entirely derived from the soil. The microbiome of insect-susceptible plants and surrounding soil tended to change towards that of insect-resistant plants after insect damage. Insects’ microbiome was mainly derived from plant stems and partly from the soil. Available potassium showed an extremely significant correlation with soil microbiome. This study validated the role played by the microbiome ecology of plant–soil-insect system in insect resistance and provided a pre-theoretical basis for crop resistance control.
Arc-driven mGRASP highlights CA1 to CA3 synaptic engrams
Authors: Murthy B. K. B. , Somatakis S. , Ulivi A. F. , Klimmt H. , Castello-Waldow T. P. , Haynes N. , Huettl R. E. , Chen A. , Attardo Alessio
Published: January 2023

Subpopulations of neurons display increased activity during memory encoding and manipulating the activity of these neurons can induce artificial formation or erasure of memories. Thus, these neurons are thought to be cellular engrams. Moreover, correlated activity between pre- and postsynaptic engram neurons is thought to lead to strengthening of their synaptic connections, thus increasing the probability of neural activity patterns occurring during encoding to reoccur at recall. Therefore, synapses between engram neurons can also be considered as a substrate of memory, or a synaptic engram. One can label synaptic engrams by targeting two complementary, non-fluorescent, synapse-targeted GFP fragments separately to the pre- and postsynaptic compartment of engram neurons; the two GFP fragments reconstitute a fluorescent GFP at the synaptic cleft between the engram neurons, thereby highlighting synaptic engrams. In this work we explored a transsynaptic GFP reconstitution system (mGRASP) to label synaptic engrams between hippocampal CA1 and CA3 engram neurons identified by different Immediate-Early Genes: cFos and Arc. We characterized the expression of the cellular and synaptic labels of the mGRASP system upon exposure to a novel environment or learning of a hippocampal-dependent memory task. We found that mGRASP under the control of transgenic ArcCreERT2 labeled synaptic engrams more efficiently than when controlled by viral cFostTA, possibly due to differences in the genetic systems rather than the specific IEG promoters.
Differential impacts of Cntnap2 heterozygosity and Cntnap2 null homozygosity on axon and myelinated fiber development in mouse
Authors: Cifuentes-Diaz Carmen , Canali Giorgia , Garcia Marta , Druart Mélanie , Manett Taylor , Savariradjane Mythili , Guillaume Camille , Le Magueresse Corentin , Goutebroze Laurence
Published: January 2023

Over the last decade, a large variety of alterations of the Contactin Associated Protein 2 (CNTNAP2) gene, encoding Caspr2, have been identified in several neuronal disorders, including neurodevelopmental disorders and peripheral neuropathies. Some of these alterations are homozygous but most are heterozygous, and one of the current challenges is to estimate to what extent they could affect the functions of Caspr2 and contribute to the development of these pathologies. Notably, it is not known whether the disruption of a single CNTNAP2 allele could be sufficient to perturb the functions of Caspr2. To get insights into this issue, we questioned whether Cntnap2 heterozygosity and Cntnap2 null homozygosity in mice could both impact, either similarly or differentially, some specific functions of Caspr2 during development and in adulthood. We focused on yet poorly explored functions of Caspr2 in axon development and myelination, and performed a morphological study from embryonic day E17.5 to adulthood of two major brain interhemispheric myelinated tracts, the anterior commissure (AC) and the corpus callosum (CC), comparing wild-type (WT), Cntnap2–/– and Cntnap2+/– mice. We also looked for myelinated fiber abnormalities in the sciatic nerves of mutant mice. Our work revealed that Caspr2 controls the morphology of the CC and AC throughout development, axon diameter at early developmental stages, cortical neuron intrinsic excitability at the onset of myelination, and axon diameter and myelin thickness at later developmental stages. Changes in axon diameter, myelin thickness and node of Ranvier morphology were also detected in the sciatic nerves of the mutant mice. Importantly, most of the parameters analyzed were affected in Cntnap2+/– mice, either specifically, more severely, or oppositely as compared to Cntnap2–/– mice. In addition, Cntnap2+/– mice, but not Cntnap2–/– mice, showed motor/coordination deficits in the grid-walking test. Thus, our observations show that both Cntnap2 heterozygosity and Cntnap2 null homozygosity impact axon and central and peripheral myelinated fiber development, but in a differential manner. This is a first step indicating that CNTNAP2 alterations could lead to a multiplicity of phenotypes in humans, and raising the need to evaluate the impact of Cntnap2 heterozygosity on the other neurodevelopmental functions of Caspr2.
Dose evaluations of organs at risk and predictions of gastrointestinal toxicity after re-irradiation with stereotactic body radiation therapy for pancreatic cancer by deformable image registration
Authors: Cao Yangsen , Zhu Xiaofei , Yu Chunshan , Jiang Lingong , Sun Yongjian , Guo Xueling , Zhang Huojun
Published: January 2023

Purpose

Re-irradiation of locally recurrent pancreatic cancer may be an optimal choice as a local ablative therapy. However, dose constraints of organs at risk (OARs) predictive of severe toxicity remain unknown. Therefore, we aim to calculate and identify accumulated dose distributions of OARs correlating with severe adverse effects and determine possible dose constraints regarding re-irradiation.

Methods

Patients receiving two courses of stereotactic body radiation therapy (SBRT) for the same irradiated regions (the primary tumors) due to local recurrence were included. All doses of the first and second plans were recalculated to an equivalent dose of 2 Gy per fraction (EQD2). Deformable image registration with the workflow “Dose Accumulation-Deformable” of the MIM® System (version: 6.6.8) was performed for dose summations. Dose–volume parameters predictive of grade 2 or more toxicities were identified, and the receiver operating characteristic (ROC) curve was used to determine optimal thresholds of dose constraints.

Results

Forty patients were included in the analysis. Only the V10 of the stomach [hazard ratio (HR): 1.02 (95% CI:1.00–1.04), P = 0.035] and Dmean of the intestine [HR: 1.78 (95% CI: 1.00–3.18), P = 0.049] correlated with grade 2 or more gastrointestinal toxicity. Hence, the equation of probability of such toxicity was P=11+e−(−4.155+0.579Dmean of the intestine+0.021V10 of the stomach) Additionally, the area under the ROC curve and threshold of dose constraints of V10 of the stomach and Dmean of the intestine were 0.779 and 77.575 cc, 0.769 and 4.22 Gy3 (α/β = 3), respectively. The area under the ROC curve of the equation was 0.821.

Conclusion

The V10 of the stomach and Dmean of the intestine may be vital parameters to predict grade 2 or more gastrointestinal toxicity, of which the threshold of dose constraints may be beneficial for the practice of re-irradiation of locally relapsed pancreatic cancer.
Combined NK-CIK and PD-1 inhibitor (nivolumab), an effective immunotherapy for treating intrahepatic lymphoepithelioma-like cholangiocarcinoma unassociated with EBV infection: Two case reports and a literature review
Authors: Sam Saji Alen , Yang Biao , Hou Wan Ting , Liu Xia , Ren Qiu Ping , Wei Yuan Feng , Zhang Yu Zu , Yang Xi
Published: January 2023

Intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC) is a very rare malignant tumor arising from the biliary epithelium. To date, there has been a lack of evidence on the radiographical features, clinicopathological features, and treatment modalities of LELCC, with less than 28 cases of LELCC without Epstein–Barr virus (EBV) infection having been reported worldwide. The treatment of LELCC remains unexplored. Here, we present two cases of patients with LELCC without EBV infection who were treated by liver resection, chemotherapy, and immunotherapy and who achieved long survival time. The patients received surgery to remove the tumors and then adjuvant chemotherapy using the GS regimen and combined immunotherapy involving natural killer–cytokine-induced killer (NK-CIK) and nivolumab were performed. Both patients had a good prognosis with a survival time of more than 100 months and 85 months.
Emerging landscape of circFNDC3B and its role in human malignancies
Authors: Sun Kai , Yao Huibao , Zhang Peizhi , Sun Yanning , Ma Jian , Xia Qinghua
Published: January 2023

In recent years, more attention has been paid to expanding the abundance of Circular RNAs (circRNAs), while the circRNAs that have been found to have significant functions have not been studied in different diseases. CircFNDC3B is one of the most researched circRNAs generated from fibronectin type III domain-containing protein 3B (FNDC3B) gene. Accumulating researches have reported the multiple functions of circFNDC3B in different cancer types and other non-neoplastic diseases, and predicted that circFNDC3B might be a potential biomarker. Notably, circFNDC3B can play roles in different diseases by binding to various microRNAs (miRNAs), binding to RNA-binding proteins (RBPs), or encoding functional peptides. This paper systematically summarizes the biogenesis and function of circRNAs, reviews and discusses the roles and molecular mechanisms of circFNDC3B and its target genes in different cancers and non-neoplastic diseases, which will do favor to broaden our comprehension of the function of circRNAs and facilitate subsequent research on circFNDC3B.
MS0621, a novel small-molecule modulator of Ewing sarcoma chromatin accessibility, interacts with an RNA-associated macromolecular complex and influences RNA splicing
Authors: Vital Tamara , Wali Aminah , Butler Kyle V. , Xiong Yan , Foster Joseph P. , Marcel Shelsa S. , McFadden Andrew W. , Nguyen Valerie U. , Bailey Benton M. , Lamb Kelsey N. , James Lindsey I. , Frye Stephen V. , Mosely Amber L. , Jin Jian , Pattenden Samantha G. , Davis Ian J.
Published: January 2023

Ewing sarcoma is a cancer of children and young adults characterized by the critical translocation-associated fusion oncoprotein EWSR1::FLI1. EWSR1::FLI1 targets characteristic genetic loci where it mediates aberrant chromatin and the establishment of de novo enhancers. Ewing sarcoma thus provides a model to interrogate mechanisms underlying chromatin dysregulation in tumorigenesis. Previously, we developed a high-throughput chromatin-based screening platform based on the de novo enhancers and demonstrated its utility in identifying small molecules capable of altering chromatin accessibility. Here, we report the identification of MS0621, a molecule with previously uncharacterized mechanism of action, as a small molecule modulator of chromatin state at sites of aberrant chromatin accessibility at EWSR1::FLI1-bound loci. MS0621 suppresses cellular proliferation of Ewing sarcoma cell lines by cell cycle arrest. Proteomic studies demonstrate that MS0621 associates with EWSR1::FLI1, RNA binding and splicing proteins, as well as chromatin regulatory proteins. Surprisingly, interactions with chromatin and many RNA-binding proteins, including EWSR1::FLI1 and its known interactors, were RNA-independent. Our findings suggest that MS0621 affects EWSR1::FLI1-mediated chromatin activity by interacting with and altering the activity of RNA splicing machinery and chromatin modulating factors. Genetic modulation of these proteins similarly inhibits proliferation and alters chromatin in Ewing sarcoma cells. The use of an oncogene-associated chromatin signature as a target allows for a direct approach to screen for unrecognized modulators of epigenetic machinery and provides a framework for using chromatin-based assays for future therapeutic discovery efforts.
Engineered octave frequency comb in integrated chalcogenide dual-ring microresonators
Authors: Wang Zifu , Luo Liyang , Xia Di , Lu Siqi , Lin Guosheng , Gao Shecheng , Li Zhaohui , Zhang Bin
Published: January 2023

Octave-spanning Kerr combs bridging the spectral windows of the near-infrared region (NIR) and the mid-infrared (MIR) region are expected in a number of applications, including high-capacity coherent optical communications, and gas molecular absorption footprints. Here, we propose novel concentric dual-ring microresonators (DRMs) for advanced dispersion engineering to tailor the comb spectral profile. The dispersion can be flexibly engineered not only by the cross-section of the DRMs, but also by the gap between concentric dual-ring microresonators, which provides a new path to geometrically control the spectral profile of the soliton Kerr combs. An octave-spanning Kerr soliton microcomb with multi-dispersive waves has been achieved numerically covering from the telecommunication band (1224 nm) to the mid-infrared band region (2913 nm) with a −40 dB bandwidth of 1265 nm. Our results are promising to fully understand the nonlinear dynamics in hybrid modes in DRMs, which helps control broadband comb formation.
Transcriptomics analysis of ethanol treatment of male Aedes aegypti reveals a small set of putative radioprotective genes
Authors: Pinch Matthew , Bendzus-Mendoza Harley , Hansen Immo A.
Published: January 2023

Introduction: Sterile Insect Technique (SIT) is based on releasing sterilized male insects into wild insect populations to compete for mating with wild females. Wild females mated with sterile males will produce inviable eggs, leading to a decline in population of that insect species. Sterilization with ionizing radiation (x-rays) is a commonly used mechanism for sterilization of males. Since irradiation can cause damage to both, somatic and germ cells, and can severely reduce the competitiveness of sterilized males relative to wild males, means to minimize the detrimental effects of radiation are required to produce sterile, competitive males for release. In an earlier study, we identified ethanol as a functional radioprotector in mosquitoes.

Methods: Here, we used Illumina RNA-seq to profile changes in gene expression of male Aedes aegypti mosquitoes fed on 5% ethanol for 48 hours prior to receiving a sterilizing x-ray dose, compared to males fed on water prior to sterilization.

Results: RNA-seq revealed a robust activation of DNA repair genes in both ethanol-fed and water-fed males after irradiation, but surprisingly few differences in gene expression between ethanol-fed and water-fed males regardless of radiation treatment.

Discussion: While differences in gene expression due to ethanol exposure were minimal, we identified a small group of genes that may prime ethanol-fed mosquitoes for improved survivability in response to sterilizing radiation.
Mapping of quantitative trait locus reveals PsXI gene encoding xylanase inhibitor as the candidate gene for bruchid (Callosobruchus spp.) resistance in pea (Pisum sativum L.)
Authors: Yan Jianjun , Chen Jingbin , Lin Yun , Yuan Xingxing , Somta Prakit , Zhang Yaowen , Zhang Zeyan , Zhang Xianhong , Chen Xin
Published: January 2023

Pea (Pisum sativum L.) is an important legume crop for both food and feed. Bruchids (Callosobruchus spp.) are destructive insect pests of pea in the field and during storage. In this study, we identified a major quantitative trait locus (QTL) controlling seed resistance to C. chinensis (L.) and C. maculatus (Fab.) in field pea using F2 populations derived from a cross between PWY19 (resistant) and PHM22 (susceptible). QTL analysis in the two F2 populations grown in different environments consistently identified a single major QTL, qPsBr2.1, controlling the resistance to both bruchid species. qPsBr2.1 was mapped onto linkage group 2 between DNA markers 18339 and PSSR202109 and explained 50.91% to 70.94% of the variation in resistance, depending on the environment and bruchid species. Fine mapping narrowed down qPsBr2.1 to a genomic region of 1.07 Mb on chromosome 2 (chr2LG1). Seven annotated genes were found in this region, including Psat2g026280 (designated as PsXI), which encodes a xylanase inhibitor and was considered as a candidate gene for bruchid resistance. PCR amplification and sequence analysis of PsXI suggested the presence of an insertion of unknown length in an intron of PWY19, which causes variation in the open reading frame (ORF) of PsXI. Moreover, the subcellular localization of PsXI differed between PWY19 and PHM22. These results together suggested that PsXI encoding xylanase inhibitor is responsible for the bruchid resistance of the field pea PWY19.
Genome-wide identification of the class III peroxidase gene family of sugarcane and its expression profiles under stresses
Authors: Shang Heyang , Fang Linqi , Qin Lifang , Jiang Hongtao , Duan Zhenzhen , Zhang Hai , Yang Zongtao , Cheng Guangyuan , Bao Yixue , Xu Jingsheng , Yao Wei , Zhang Muqing
Published: January 2023

Introduction

Plant-specific Class III peroxidases (PRXs) play a crucial role in lignification, cell elongation, seed germination, and biotic and abiotic stresses.

Methods

The class III peroxidase gene family in sugarcane were identified by bioinformatics methods and realtime fluorescence quantitative PCR.

Results

Eighty-two PRX proteins were characterized with a conserved PRX domain as members of the class III PRX gene family in R570 STP. The ShPRX family genes were divided into six groups by the phylogenetic analysis of sugarcane, Saccharum spontaneum, sorghum, rice, and Arabidopsis thaliana. The analysis of promoter cis-acting elements revealed that most ShPRX family genes contained cis-acting regulatory elements involved in ABA, MeJA, light responsiveness, anaerobic induction, and drought inducibility. An evolutionary analysis indicated that ShPRXs was formed after Poaceae and Bromeliaceae diverged, and tandem duplication events played a critical role in the expansion of ShPRX genes of sugarcane. Purifying selection maintained the function of ShPRX proteins. SsPRX genes were differentially expressed in stems and leaves at different growth stages in S. spontaneum. However, ShPRX genes were differentially expressed in the SCMV-inoculated sugarcane plants. A qRT-PCR analysis showed that SCMV, Cd, and salt could specifically induce the expression of PRX genes of sugarcane.

Discussion

These results help elucidate the structure, evolution, and functions of the class III PRX gene family in sugarcane and provide ideas for the phytoremediation of Cd-contaminated soil and breeding new sugarcane varieties resistant to sugarcane mosaic disease, salt, and Cd stresses.
Threshold effects of green technology application on sustainable grain production: Evidence from China
Authors: Li Jingdong , Lin Qingning
Published: January 2023

Sustainable production is considered as an important approach to solve the dilemma of food insecurity. Green technologies have made contributions to improving food production and reducing environmental pollution. Studying the effects of green technologies on sustainable food production has great significance. The paper started with the influence mechanism of green technology application on the green total factor productivity of grain (GTFPG). With the GTFPG, green technology efficiency change of grain (GECG) and green technical progress change of grain (GTCG) measured, threshold models were constructed to explore the nonlinear impacts of various green technologies on GTFPG and the influence paths. Results indicated that the differences of GTFPG among provinces in China were decreased mainly due to the changes of GTCG, while the regional differences of GECG remained small. The impacts of green technologies had threshold effects that depended on the ecological effects of green technologies in different application stages, and were significantly different in the major and non-major grain producing areas. Meanwhile, significant differences existed in the influence paths of green technologies. In the major grain producing areas, green technologies were more likely to improve GTFPG through the GTCG path; while in the non-major grain producing areas, the GECG path and the GTCG path were both important to improve GTFPG. The differences of green technologies’ threshold effects and influence paths in the major and non-major grain producing areas were caused by regional technology preference, resource endowment and technology compatibility. This study emphasizes that the development of green technologies should fully consider the resource endowment and economic development of different regions, as well as the applicability and adoption rate of green technologies.
Beat alignment ability is associated with formal musical training not current music playing
Authors: Spiech Connor , Endestad Tor , Laeng Bruno , Danielsen Anne , Haghish E. F.
Published: January 2023

The ability to perceive the beat in music is crucial for both music listeners and players with expert musicians being notably skilled at noticing fine deviations in the beat. However, it is unclear whether this beat perception ability is enhanced in trained musicians who continue to practice relative to musicians who no longer play. Thus, we investigated this by comparing active musicians’, inactive musicians’, and nonmusicians’ beat alignment ability scores on the Computerized Adaptive Beat Alignment Test (CA-BAT). 97 adults with diverse musical experience participated in the study, reporting their years of formal musical training, number of instruments played, hours of weekly music playing, and hours of weekly music listening, in addition to their demographic information. While initial tests between groups indicated active musicians outperformed inactive musicians and nonmusicians on the CA-BAT, a generalized linear regression analysis showed that there was no significant difference once differences in musical training had been accounted for. To ensure that our results were not impacted by multicollinearity between music-related variables, nonparametric and nonlinear machine learning regressions were employed and confirmed that years of formal musical training was the only significant predictor of beat alignment ability. These results suggest that expertly perceiving fine differences in the beat is not a use-dependent ability that degrades without regular maintenance through practice or musical engagement. Instead, better beat alignment appears to be associated with more musical training regardless of continued use.
The phenotype of type 1 diabetes in sub-Saharan Africa
Authors: Katte Jean Claude , McDonald Timothy J. , Sobngwi Eugene , Jones Angus G.
Published: January 2023

The phenotype of type 1 diabetes in Africa, especially sub-Saharan Africa, is poorly understood. Most previously conducted studies have suggested that type 1 diabetes may have a different phenotype from the classical form of the disease described in western literature. Making an accurate diagnosis of type 1 diabetes in Africa is challenging, given the predominance of atypical diabetes forms and limited resources. The peak age of onset of type 1 diabetes in sub-Saharan Africa seems to occur after 18–20 years. Multiple studies have reported lower rates of islet autoantibodies ranging from 20 to 60% amongst people with type 1 diabetes in African populations, lower than that reported in other populations. Some studies have reported much higher levels of retained endogenous insulin secretion than in type 1 diabetes elsewhere, with lower rates of type 1 diabetes genetic susceptibility and HLA haplotypes. The HLA DR3 appears to be the most predominant HLA haplotype amongst people with type 1 diabetes in sub-Saharan Africa than the HLA DR4 haplotype. Some type 1 diabetes studies in sub-Saharan Africa have been limited by small sample sizes and diverse methods employed. Robust studies close to diabetes onset are sparse. Large prospective studies with well-standardized methodologies in people at or close to diabetes diagnosis in different population groups will be paramount to provide further insight into the phenotype of type 1 diabetes in sub-Saharan Africa.
Resistance-resistant antibacterial treatment strategies
Authors: Batchelder Jonathan I. , Hare Patricia J. , Mok Wendy W. K.
Published: January 2023

Antibiotic resistance is a major danger to public health that threatens to claim the lives of millions of people per year within the next few decades. Years of necessary administration and excessive application of antibiotics have selected for strains that are resistant to many of our currently available treatments. Due to the high costs and difficulty of developing new antibiotics, the emergence of resistant bacteria is outpacing the introduction of new drugs to fight them. To overcome this problem, many researchers are focusing on developing antibacterial therapeutic strategies that are “resistance-resistant”—regimens that slow or stall resistance development in the targeted pathogens. In this mini review, we outline major examples of novel resistance-resistant therapeutic strategies. We discuss the use of compounds that reduce mutagenesis and thereby decrease the likelihood of resistance emergence. Then, we examine the effectiveness of antibiotic cycling and evolutionary steering, in which a bacterial population is forced by one antibiotic toward susceptibility to another antibiotic. We also consider combination therapies that aim to sabotage defensive mechanisms and eliminate potentially resistant pathogens by combining two antibiotics or combining an antibiotic with other therapeutics, such as antibodies or phages. Finally, we highlight promising future directions in this field, including the potential of applying machine learning and personalized medicine to fight antibiotic resistance emergence and out-maneuver adaptive pathogens.
A new dynamic word learning task to diagnose language disorder in French-speaking monolingual and bilingual children
Authors: Matrat Mélodie , Delage Hélène , Kehoe Margaret
Published: January 2023

Tools to effectively assess the language performance of bilingual children are lacking. Static tests assessing vocabulary knowledge (e.g., naming task) are not appropriate for testing bilingual children due to different types of bias. Alternative methods have been developed to diagnose bilingual children, including measuring language learning (e.g., word learning) through dynamic assessment. Research conducted with English-speaking children indicates that DA of word learning is effective in diagnosing language disorders in bilingual children. In this study, we examine whether a dynamic word learning task, using shared-storybook reading, can differentiate French-speaking (monolingual and bilingual) children with developmental language disorder (DLD) from those with typical development (TD). Sixty children (4–8 years), 43 with TD and 17 with DLD, participated: 30 were monolinguals and 25 were bilinguals. The dynamic word-learning task used a shared-storybook reading context. The children had to learn four non-words, paired with novel objects, as well as their semantic characteristics (a category and a definition) during the reading of a story. Post-tests assessed the recall of the phonological form and the semantic features of the objects. Phonological and semantic prompts were given if the child was unable to name or describe the objects. Results indicated that children with DLD performed less well than those with TD on phonological recall, leading to fair sensitivity and good specificity at delayed post-test for young children (4–6 years). Semantic production did not differentiate the two groups: all children performed well at this task. In sum, children with DLD have more difficulties encoding the phonological form of the word. Our findings suggest that a dynamic word learning task using shared-storybook reading is a promising approach for diagnosing lexical difficulties in young French-speaking, monolingual and bilingual, children.
Modeling of Underactuated Ball and Beam System—A Comparative Study
Authors: Gembalczyk Grzegorz , Domogała Paweł , Leśniowski Kamil
Published: January 2023

The article presents a comparison of the methods of modeling the underactuated ball and beam system. This study was carried out to select a model suitable for the development of a control system using the model-based design methodology. Firstly, the approach commonly used in research was verified. It was also examined whether it is important to take into account the eccentric fixation in these models. An original model taking into account friction resistance was also proposed. The considered models were simulated in Matlab/Simulink software environments and verified in reality. The obtained results were compared and analyzed.
Analysis and Structure Optimization of Scissor-Type Micro-Stirrer with the Most Effective Output Performance for Thrombus Dissolution in Interventional Therapy
Authors: Yang Jingjing , Rong Benyang , Wang Lei , Morita Minoru , Deng Guifang , Jiang Yifan , Qian Junbing
Published: January 2023

Compared with thrombus dissolution using only thrombolytic agents, an advanced therapy of direct stirring of the blood clot can yield shorter recanalization time and higher recanalization velocity. Our previous research presented the design of a novel micro-stirrer, which can convert longitudinal vibration into transverse vibration and eventually generate opposite transverse vibration at the end-effort, like a scissor, for efficient blood clot stirring and thrombus dissolution acceleration. Transverse vibration is the most effective movement to dissolve thrombi. However, the small size of blood vessels has strict limits, which will greatly affect the output transverse vibration. Therefore, to improve the output performance of the micro-stirrer in curved and narrow vascular spaces, the analysis and structure optimization of the micro-stirrer is expected to increase the vibration mode conversion efficiency from longitudinal to transverse mode. The design concept and theoretical analysis of the micro-stirrer are presented in detail. Aiming to obtain the optimal structure parameters of the micro-stirrer, the mathematical model is established and analyzed. Next, a series of finite element models involving important structure parameters are designed and investigated. Finally, the optimal structure parameters are obtained, and the stirring effect in a blood vessel is verified by simulation and experiment.