bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyber-Terrorism of ISIS and The Challenge Towards Global Security
Authors: Margiati Titis , Qodarsasi Umi
Published: January 2023

Terrorism activities are no longer carried out traditionally, but have adopted a more modern way by utilizing information technology. Terror groups have even launched recruitment and fundraising processes for terrorist activities through electronic media. This paper aims to identify how ISIS uses cyberspace to carry out its acts of terrorism and how global initiatives are to tackle cyberterrorism. This study used a qualitative descriptive approach. This research data was obtained based on a literature review sourced from previous research in the form of journals, books and other scientific works that are relevant to the topic of discussion. The result of this paper is ISIS uses cyberspace for several purposes, including propaganda dissemination, global recruitment, fundraising, publication, attack planning, and other activities to increase its existence. To fights against international terrorism requires counter-terrorism that based on partnership between all levels of governments, communities and the private sectors. In a globalised, interdependent world, our multilateral, regional and bilateral partnerships have proven critical to achieving global security and counter-terrorism objectives. As a commitment to global cyber security, the United Nations builds technical capacity and prepares guidelines for member countries to anticipate crimes in cyberspace, including cyberterrorism.
PRESERVED MEMBRANE ON DINOSAUR EGGSHELL FRAGMENTS, UPPER JURASSIC MORRISON FORMATION, EASTERN UTAH
Authors: LAZER KAYLA , STOUT IAN P. , SIMPSON EDWARD L. , WIZEVICH MICHAEL C. , KEEBLER ABIGAL M. , HETRICK GRACE K.
Published: January 2023

Dinosaur eggshell fragments, from the Upper Jurassic Brushy Basin Member of the Morrison Formation, Utah, were examined using Field Emission Scanning Electron Microscope (FESEM), Energy Dispersive Spectroscopy, and Raman Spectroscopy. Analyses revealed that the mammillary tips on the shell interior contain carbonaceous residue. Comparison under the FESEM of these shells with modern bird shells, including some samples heated to diagenetic temperatures, indicate that the residue is degraded organic compounds (DOC). Bird egg membrane is composed of interlaced collagen fibers. Features observed on, and common to, modern bird and dinosaur egg fragments include: (1) irregular-shaped calcium carbonate grains “floating” in an organic matrix; (2) three-dimensional organic fiber matrix; (3) external calcium carbonate molds of fibers in the mammillary bodies; and in heated specimens, (4) carbonaceous residue with ovate to circular pores. However, unlike birds' eggs, the dinosaur eggs contain a calcium carbonate tube around fibrous organic material that emerges from the tube and spreads laterally in a ‘puddle-like' deposit. The sizes of circular organic matrix pores of the dinosaur egg fragments are significantly smaller than those in the bird shells. Gallus gallus domesticus eggshell membranes heated to diagenetic temperatures resulted in alteration of collagen fibers to gel-like substances. The organic matrix with ovate to circular pore openings and the puddle-like deposits in the dinosaur egg fragments are interpreted as the product of membrane thermal diagenesis. The recognition of carbonaceous residue of the shell membrane on dinosaur shell fragments opens newfound opportunities to explore DOC associated with fragmental dinosaur eggs.
Efectividad de las intervenciones psicológicas en Trastorno del Espectro Autista: una revisión sistemática de meta-análisis y revisiones sistemáticas
Authors: Flujas-Contreras Juan Miguel
Published: January 2023

El presente trabajo tiene como objetivo evaluar la efectividad de las intervenciones psicológicas en niños con diagnóstico de Trastorno del Espectro Autista (TEA). Se ha seguido un diseño de revisión de revisiones en el que se han incluido publicaciones de revisión sistemática y meta-análisis que revisaban intervenciones psicológicas en niños con TEA con el objetivo de mejorar la sintomatología, el funcionamiento o el bienestar y calidad de vida de estas personas. La búsqueda se ha realizado en las bases de datos PubMed, Web of Science, The Cochrane Library y Prospero, con limitación temporal de publicaciones en los últimos 5 años. El riesgo de sesgos de los estudios seleccionados fue evaluado mediante el instrumento A Measurement Tool to Assess Systematic Reviews (AMSTAR-2). Se han analizado 8 estudios de revisión sistemática y meta-análisis. El análisis según el modelo terapéutico reporta que la terapia cognitivo conductual es útil para el manejo de síntomas de ansiedad en TEA de alto funcionamiento. La terapia de conducta es efectiva para la mejora de la comunicación, las interacciones sociales, habilidades de autonomía y la inteligencia. En los estudios analizados se presenta una amplia heterogeneidad de variables y medidas de evaluación, así como de programas y estrategias de intervención con programas de tratamiento combinados, que no permite llegar a conclusiones definitivas sobre la efectividad de programas concretos. Se concluyen ciertos puntos clave como directrices de intervención en autismo.
Creación de una empresa de plataforma tecnológica - Mil oficios
Authors:   , Arroyo Castillo Dayana Ivon
Published: January 2023

El mercado del servicio técnico para el hogar ha sido una industria muy poco explorada por actores formales en la actualidad. Ante una reputación donde se perpetua la desconfianza, el incumplimiento, la informalidad y la inseguridad, conseguir un técnico de confianza suele ser una tarea de mucha dificultad. La demanda de estos servicios ha sido cubierta de manera familiar o mediante conocidos de confianza, pero ante una generación que no tiende a tener habilidades domésticas, queda abierta una necesidad que de enfocarse de manera correcta puede tener un posicionamiento de alta escalabilidad. El modelo de conexión mediante demandante y ofertante por medio de una aplicación ha mostrado tener casos bastante exitosos, configurándose como el estándar en la contratación de pequeños servicios en la actualidad. El presente plan apunta al diseño de un modelo de negocios para la creación de una aplicación que vincule a personas con necesidades de servicio técnico doméstico con técnicos calificados ofertantes. Se inicia con un análisis del entorno mediante la metodología PEST para el desarrollo de un FODA cruzado. Posteriormente, se valida la idea de negocio mediante un estudio de mercado que presenta con claridad que existe una brecha en la demanda, evidenciando las condiciones para la entrada de un nuevo competidor. Se define el marco estratégico de la empresa, determinando la misión, visión y valores para proceder con la confección de un plan de marketing mediante un marketing mix. Para la consecución del servicio ofrecido en el plan de marketing, se diseña un plan de operaciones donde se detalla todo el proceso productivo y la estructura organizacional que lo soporta e un plan de recursos humanos. Finalmente, las proyecciones son consolidadas en un plan económico y financiero donde se analizan los principales estados financieros proyectados y sus ratios para evaluar la viabilidad del proyecto.
An update to: Tracking TAU in neurons: How to transfect and track exogenous TAU in primary neurons
Authors: Buchholz Sarah , Bell-Simons Michael , Zempel Hans
Published: January 2023

Primary murine neurons have proved to be an essential tool for the general investigation of neuronal polarity, polarized TAU distribution, and TAU-based neuronal dysfunction in disease paradigms. However, mature primary neurons are notoriously difficult to transfect with non-viral approaches and are very sensitive to cytoskeletal manipulation and imaging. Furthermore, standard non-viral transfection techniques require the use of a supportive glia monolayer or high-density cultures, both of which interfere with microscopy. Here we provide a simple non-viral liposome-based transfection method that enables transfection of TAU in low levels comparable to endogenous TAU. This allows the investigation of e.g., distribution and trafficking of TAU, without affecting other cytoskeleton-based parameters such as microtubule density or microtubule-based transport. Using this protocol, we achieve a profound transfection efficiency, but avoid high overexpression rates. Importantly, this transfection method can be applied to neurons at different ages and is also suitable for very old cultures (up to 18 days in vitro). In addition, the protocol can be used in cultures without glial support and at suitable cell densities for microscopy-based single-cell analysis. In sum, this protocol has proven a reliable tool suitable for most microscopy-based approaches in our laboratory.
Understanding the Potential of Light Absorption in Dots-in-Host Semiconductors
Authors: Alexandre Miguel , Águas Hugo , Fortunato Elvira , Martins Rodrigo , Mendes Manuel J.
Published: January 2023

The outstanding physical properties of dots-in-host (QD@Host) hetero semiconductors demand detailed methods to fundamentally understand the best routes to optimize their potentialities for different applications. In this work, a 4-band k.p-based method was developed for rocksalt QDs that describes the complete optical properties of arbitrary QD@Host systems, trailblazing the way for the full opto-electronic analysis of quantum-structured solar cells. Starting with the determination of the QD bandgap, and validation against well-established literature results, the electron transition rate is then computed and analysed against the main system parameters. This is followed by a multi-parameter optimization, considering intermediate band solar cells as a promising application, where the best QD configuration was determined, together with the corresponding QD@Host absorption spectrum, in view of attaining the theoretical maximum efficiency (~ 50%) of this photovoltaic technology. The results show the creation of pronounced sub-bandgap absorption due to the electronic transitions from/to the quantum-confined states, which enables a much broader exploitation of the sunlight spectrum.
The Study of Absoluteness Overlooked by Special Relativity
Authors: Koh Hyoungseok
Published: January 2023

This study has reinterpreted the relativity of the laws of physics, an axiom of the special theory of relativity. Einstein interpreted that the relativity of the laws of physics is established due to the relativity of the inertial system. However, he did not consider that relativity was established despite the absoluteness of the inertial system being established. In this paper, we have assumed that relativity holds despite the absoluteness of the inertial system. This perspective is called observer relativity and is used distinguish it from the relativity of the inertial system. Relativity between the observers is expressed using the Lorentz and inverse transform since lights are used by the observers in both cases. To prove the absoluteness of the inertial system, a rigid ruler and light are used. If the observers measure the length with a rigid ruler and light, the reference system is consistent but the system of motion is different. This is defined as the absoluteness of the inertial system. To prove this absoluteness, several experiments were conducted to measure the electrostatic force between two electric charges fixed at the same distance. If the isotropy of space is satisfied, a stationary system can be defined. Conversely, it is defined as a constant velocity system. In the inertial system, the relativity between observers and absoluteness of the inertial system coexist.
High-depth whole-genome sequencing identifies structure variants, copy number variants and short tandem repeats associated with Parkinson’s disease
Authors: Chan Piu , Wang Chaodong , Liu Hankui , Li Xu-Ying , Ma Jinghong , Gu Zhuqin , Feng Xiuli , Xie Shu , Tang Beisha , Chen Shengdi , Wang Wei , Wang Jian , Zhang Jianguo
Published: January 2023

While numerous single nucleotide variants and small indels have been identified in Parkinson’s disease (PD), the genome-wide contribution of structural variants (SVs), copy number variants (CNVs) and short tandem repeats (STRs) remains poorly understood. Here we investigated the association between these variants and PD using the high-depth whole-genome sequencing data from 466 PD patients and 513 healthy elderlies. A total of 29,561 SVs, 32,153 CNVs and 174,905 STRs were detected. Overall, CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. Genome-wide association study identified 11 novel signals (1 SV, 4 CNVs and 6 STRs) reaching genome-wide significance. Among these, the deletion nearby MUC19 and the 5-copy GGGAAA repeat in SLC2A13 reduced the penetrance of LRRK2 G2385R variant. Moreover, genes with these variants were specifically expressed in dopaminergic neurons and highly dosage-sensitive. These data provided novel insights into the genetic architecture of PD.
Unprecedented 2022 Yangtze River Valley heatwaves linked to the record-breaking Pakistan flood and triple-dip La Niña
Authors: Qiao Shaobo , Tang Shankai , Wang Bin , Liu Fei , Feng Taichen , Yang Jie , He Meng , Chen Dong , Cheng Jianbo , Feng Guolin , Dong Wenjie
Published: January 2023

In July-August 2022, Yangtze River valley (YRV) experienced unprecedented hot summer, with the number of heatwave days exceeding climatology by four standard deviations. The heatwaves and associated severe droughts affected about 38 million people and caused devastating economic losses of about five billion US dollars. Here we present convergent empirical and modelling evidence to show that the record-breaking Pakistan rainfall, along with the 2022 tripe-dip La Niña, produces anomalous high pressure over YRV, causing intense heatwaves. The La Niña-induced second-highest sea surface temperature gradient in the equatorial western Pacific suppresses western Pacific convection and extends the subtropical high westward. More importantly, the tremendous diabatic heating associated with the unprecedented Pakistan rainfall reinforces the downstream Rossby wave train, extending the upper-level South Asia High eastward and controlling the entire YRV. The overlay of the two high-pressure systems sustains sinking motion and increases solar radiation reaching the ground, causing recurrent heat waves.
Proportion of vitamin D deficiency in children/adolescents with type 1 diabetes: A systematic review and meta-analysis
Authors: Yang Xin , Chai Min , Lin Meng
Published: January 2023

Background: The impact of vitamin D on type 1 diabetes has been a controversial topic in public health. Furthermore, significant differences in the proportion of vitamin D have been noted. The purpose of this systematic review was to determine the overall proportion of vitamin D deficiency in children/adolescents with type 1 diabetes (T1D).
Methods: Based on six electronic databases (PubMed, Web of Science, Embase, Ovid Medline, ProQuest, and Cochrane Library), eligible studies since the databases’ inception up to April 2022 were searched. Reference lists were also manually searched to identify additional studies. Overall, studies with statistical information on vitamin D deficiency in children and adolescents with T1D were included, and a random effects model was applied for the meta-analysis. In addition, subgroup and sensitivity analyses were carried out to evaluate heterogeneity, and publication bias was evaluated by using Egger’s test.
Results: A total of 45 studies involving 6,995 participants were selected for the meta-analysis. The proportion of vitamin D deficiency in children/adolescents with T1D was found to be 45% (95% confidence interval [CI] 37-54%, I2 = 97.94%). Subgroup analysis further showed that the publication year, study design, classification of vitamin D, different seasons and geographical region could significantly contribute to variations in the reported proportion of vitamin D deficiency.
Conclusions: This systematic review analyzed the available literature and revealed that the proportion of vitamin D deficiency among T1D children/adolescents was 45%. In addition, the proportion remains higher, which has important implications for adapting health and social care systems.
A Large-Dynamic-Range Violet Phosphorus Heterostructure Optoelectronic Synapse for High-Complexity Neuromorphic Computing
Authors: Liu Xiaoxian , Wang Shuiyuan , Di Ziye , Wu Haoqi , Liu Chunsen , Zhou Peng
Published: January 2023

Neuromorphic computing can efficiently handle data-intensive tasks and address the redundant data interaction required by traditional von Neumann architectures. Synaptic devices are essential components for neuromorphic computation. For high computational accuracy, synaptic devices need to retain good conductance linearity, but this leads to a limited dynamic range (10 ~ 100) and weight states, which impedes their processing of high-complexity tasks and restricts further advances in accuracy. Two-dimensional materials, such as transition metal disulfides and phosphorene, hold promise for the construction of synaptic devices with large dynamic ranges due to their strong light-matter interactions, while the stability of phosphorene remains an issue. Here, for the first time, we use the most stable violet phosphorene for device applications. The combination of violet phosphorene and molybdenum disulfide demonstrates an optoelectronic synapse with a record dynamic range of over 106, benefiting from a significant threshold shift due to charge transfer and trapping in the heterostructure. Remarkable synaptic properties are demonstrated, including 128 distinguishable conductance states, electro-optical dependent plasticity, short-term paired-pulse facilitation, and long-term potentiation/depression. High-precision image classification with accuracies of 95.23% and 79.65% is achieved for MNIST and high-complexity Fashion-MNIST datasets, which is close to the ideal device (95.47%, 79.95%), indicating the potential of dynamic range and multi-states for optimizing accuracy. This work fills the device application gap of violet phosphorene and provides a strategy for building synaptic devices with large dynamic range to facilitate neuromorphic computing.
CD4highCD8low double-positive T cells with high differentiation mediate incomplete immune reconstitution in HIV-infected patients
Authors: Zhao Yu , Jia Jie , Zhang Yizhi , Mou Tangwei , Zhao Qi-Hui , Kong Deshenyue , Li Shao-You , Yang Ji-Qun , Mao Jun-Hong , Zhang Xiu-Ling , Su Bin , Kuang Yi-Qun
Published: January 2023

Antiretroviral therapy (ART) is the most generally used to treat human immunodeficiency virus (HIV)-infected patients. However, some patients experience incomplete immune reconstitution and fail to restore CD4+ T cell counts after treating with ART. Herein, we investigated the characters of CD4+CD8+ double-positive (DP) T cells at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from HIV-infected immunological non-responders (INRs) and immunological responders (IRs). We identified eight DP T cell clusters and grouped into three populations CD4highCD8low, CD4lowCD8high, and CD4lowCD8low, respectively. Decreased proportion of DP T cells was detected in INRs, including CD4highCD8low DP T cells in the process of cellular differentiation, the latter demonstrated a reduced source of DP T cells in INRs. CD4highCD8low DP T cells in IRs and INRs as a heterogenous population, were distinct on the expression of GZMA/B/H, LAG3, NKG7 and GNLY, which related to the function of cell activation and cellular differentiation, cytotoxicity and programmed cell death. These data provide a comprehensive analysis of gene signatures of CD4highCD8low DP T cells associated with failed immune reconstitution after HIV infection, which could be useful in developing new cure strategies for HIV-infected patients.
Low-cost pathways to synthesize silica-smectite clay-based composites
Authors: Kepdieu Jean Marie , Djangang Chantale Njiomou , Njimou Jacques Romain , Maicaneanu Sanda Andrada , Mache Jacques Richard
Published: January 2023

The present study aimed at using rice husk as a natural silica precursor in the fabrication of silica-smectite composites. A local smectite clay was respectively mixed with 1) silica sludge from rice husk ashes after an acid treatment, 2) an aqueous sodium silicate solution from alkaline dissolution of silica sludge and 3) a nanosilica powder obtained after hydroxylation/polymerisation of a sodium silicate solution. Products from the three different synthesis pathways were investigated by XRD, infrared spectrometry, SEM/EDX and BET specific surface measurement. They show a heterogeneous morphology where the distribution of silica particles in the clay matrix change with each synthesis pathway. For silica sludge synthesis pathway, a predominated three-dimensional-like structure with a phyllosilicate matrix skeleton was obtained. For the pathway using a silicate solution, we obtained an amorphous compound having a limited intergranular cohesion and containing silicate agglomerates that are intercalated between clay sheets. It is different for the nanosilica reinforced pathway that led to a packed morphology with a regular distribution of silica phases in the clay matrix. In all the synthesized composites, we observe the occurrence of amorphous silica phases that favours both the existence of porosity and the presence of chemically active sites. Consequently, obtained products are potential multifunctional materials.
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory T cell differentiation in vitro
Authors: Tarasenko Tatiana N. , Banerjee Payal , Gomez-Rodriguez Julio , Gildea Derek , Zhang Suiyuan , Wolfsberg Tyra , Jenkins Lisa M. , Program NISC Comparative Sequencing , McGuire Peter J.
Published: January 2023

Background
Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node.
Methods
To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. To control for the contribution of exogenous metabolites in vivo, we conducted our T cell functional studies in vitro. T cells were differentiated into memory and effector T cells using standardized protocols. Cells were analyzed using stable isotopic tracing studies, metabolomics, RNAseq, ATACseq, ChIPseq and histone proteomics.
Results
Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. Due to depressed OXPHOS, TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis. Due to the block of PDC activity, histone acetylation was reduced, as were most other types of post translational modifications. Transcriptional and functional profiling revealed abnormal CD8+ memory T cell differentiation in vitro.
Conclusions
Collectively, our data indicate that PDC integrates the metabolome and epigenome in memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.
SET-mediated epigenetic dysregulation of p53 impairs Trichloroethylene-induced DNA damage response
Authors: ren Xiaohu , Ruan Jiawen , Yang Sixia , Lan Xuerao , Wu Desheng , Huang Xinfeng , Zhang Hongyu , Huang Haiyan , Liu Jianjun
Published: January 2023

Trichloroethylene (TCE) is a major ground water pollutant which causes severe hepatic toxicity. Previously, we have identified histone chaperon, SET as a key mediator of TCE-induced liver cell apoptosis. DNA damage with p53 suppression and reduced tri-methylation at histone H3K79 (H3K79me3) were also found under the treatment of TCE. However, epigenetic mechanisms in TCE-associated DNA damage response still remain largely unknown. In this study, we evaluated TCE-induced DNA damage of hepatic cells in the absence of SET, analyzed levels of H3K79me3 and p53 in hepatic cells and in mice livers with carcinogenesis. Results suggested that SET partially suppressed H3K79me3 and interfering with DNA response via mediating down-regulation of p53 under treatment of TCE. To further figure out the regulatory cascade, DoT1L (regulator of H3K79me3) and p53 were knocked down in L-02 cells respectively. Additionally, extent of DNA damage along with alterations of H3K79me3 and p53 were also evaluated. Results indicated that reduced H3K79me3 could lead to down-regulation of p53 which further exacerbated TCE-induced DNA injury. These findings demonstrated that SET-H3K79me3-p53 served as an epigenetic regulatory axis involved in TCE-induced DNA damage response.
Trichomes on Cotton Leaf Surface Affect the Feeding Behaviors of Cotton Aphids
Authors: Yang Muzhi , Liu Chunyan , Zhao Tianyi , Li Yichao , Liu Huayan , Ren Zhentao , Xue Kun
Published: January 2023

Aphis gossypii Glover is one of the most important pests in cotton seedling. The specialized mouthpart and short generation time allow them seriously restricted the quality and yield of cotton. With the electrical penetration graph (EPG), optical microscope, and scanning electron microscope, the physical characteristics of trichomes on the cotton leaf surface and their effects on the feeding behaviors of cotton aphids were investigated in this study. Two types of leaf trichomes, glandular trichomes, and asteroid non-glandular trichomes were observed on the surface of cotton leaves under optical and scanning electron microscopes. As a whole, EPG results mainly showed differences in a non-probe waveform which meant searching on the leaf surface, and a potential drop waveform which meant intracellular penetration. Whereas pathway waveform, xylem waveform, and phloem waveform showed inconspicuous differences. Detailed indicators were slightly different at different periods. Our results confirmed that the structure of trichomes may directly affect the searching behaviors of herbivorous insect pests and hence regulate the plant-environment interactions.
Prediction of construction material prices using ARIMA and multiple regression models
Authors: Hosny Suad , Elsaid Elshaimaa , hosny Hossam
Published: January 2023

Construction Material Prices (CMP) variations have become a major issue in properly budgeting construction projects. Inability to accurately forecast CMP volatility can also lead to price overestimation or underestimation. Enhancing the accuracy of predictions of CMP can also enhance the accuracy of predictions of total construction costs. The purpose of this study is to present a model for predicting construction material prices that assist decision-makers to make better decisions over the life cycle of a project. The price records for CMP namely; steel, cement, brick, ceramic, and gravel, and the indicators affecting them in Egypt were used for the prediction procedures. The practical methods for using the Box-Jenkins approach Autoregressive Integrated Moving Average (ARIMA) time series and multiple regression models for forecasting building material prices are outlined in this research. Out-of-sample predictions are used to evaluate the provided model's performance in predicting future prices. The models are compared according to the Mean Absolute Percentage Errors (MAPE). The generated models show good results in predicting month-to-month variations in material prices, with MAPE ranging from 1.4 to 2.8 percent for the selected models. This research can assist both owners and contractors in improving their budgeting processes, and preparing more accurate cost estimates.
Simple and selective extraction of quercetin with MEPS method using modified glass powder by a molecularly imprinted polymer followed by spectrophotometric determination
Authors: sharifi Arman , hallaj Rahman , bahar Soleiman
Published: January 2023

A new sample preparation method based on microextraction in packed syringe (MEPS) was
developed for preconcentration of quercetin prior to its spectrophotometric determination. Molecularly imprinted polymers (MIPs) as packing material was used for higher extraction efficiency. First, Glass powder as support material because of low-cost and available substrate were modified and then MIPs synthesized by the sol-gel method using 3 aminopropyltriethoxysilane (APTES) as a functional monomer and tetraethyl orthosilicate (TEOS) as cross-linker. The combination of a molecularly imprinted polymers (MIPs) and microextraction in packed syringe (MEPS) increased the selectivity and sensitivity. The surface morphology and functionality of the prepared MIPs was characterized using Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM) and Thermogravimetric analysis (TGA). Different influencing parameters on extraction efficiency such as effect of the number of sample sorption/desorption cycles, type and volume of desorption solvent, pH of the sample solution and MIP amounts were optimized. Under the optimum condition, the proposed method displayed a linear range from 0.01 to 5 μg mL-1 and detection limit of 3.68 ng mL-1. Relative standard deviations (RSD) for 3 replicate determination of 1 μg mL-1 quercetin was 2.1 %. The proposed method was applied successfully for the selective extraction of quercetin from tea and coffee samples.
Hair cortisol as a biomarker for mood in bipolar disorder: a pilot study
Authors: Maimon Lior , Milo Tomer , Haran Dafna , Cohen Ben , Danon Tamar , Bren Anat , Mayo Avi , Rappaport Gadi Cohen , Alon Uri
Published: January 2023

Background
Bipolar disorder (BD) is characterized by episodes of manic, depressive and mixed mood states which have profound effects on the patient's quality of life. BD is diagnosed and followed up clinically using psychiatric assessment, with currently no biomarkers in clinical use for diagnosis or follow-up of the disorder. One potential biomarker is the stress hormone cortisol, but this has not been tested by comparing mood and cortisol within a cohort of people with BD. Here we asked whether hair cortisol might serve as a biomarker for mood in BD, with its advantage of averaging cortisol over months, bypassing concerns of circadian rhythm and acute stresses.
Methods
We measured cortisol in 2cm hair segments proximal to the scalp, which correspond to two months of hair growth. At the time hair was harvested, participants with BD were scored for depression and anxiety using the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). We calculated partial Pearson correlations between mood scales and hair cortisol levels, accounting for participant’s age, gender, family status, education and medication.
Results
Hair cortisol correlated positively with mood scores in all three scales (r = 0.45–0.55, n = 38, p < = 0.01).
Conclusions
We conclude that hair cortisol may be a useful candidate biomarker for mood of BD patients over recent months.
Senescent cells develop PDK4-dependent hypercatabolism and produce lactate to promote cancer resistance and aging
Authors: Dou Xuefeng , Fu Qiang , Long Qilai , Liu Shuning , Zou Yejun , Fu Da , Xu Qixia , Jiang Zhirui , Ren Xiaohui , Zhang Guilong , Wei Xiaoling , Li Qingfeng , Campisi Judith , Zhao Yuzheng , Sun Yu
Published: January 2023

Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here we highlight upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon cellular senescence, a tendency adversely correlated with cancer patient survival after chemotherapy. Senescent cells exhibit increased aerobic glycolysis and enhanced lactate production, but subject to reversal upon PDK4 inhibition. Distinct from the cancer cell-featured Warburg effect, however, senescent cells sustain mitochondrial respiration and redox activity, adopting a special form of metabolic reprogramming. Media from PDK4+ stromal cells change global expression and promote malignancy of recipient cancer cells in vitro, while targeting PDK4 causes tumor regression in vivo. The metabolite lactate causes NOX1 upregulation and ROS production in mitochondrion-disabled cells, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype (SASP). In preclinical trials, PDK4 intervention alleviates physical dysfunction and prevents age-associated frailty, conditions frequently observed in advanced life. Together, our study substantiates the hypercatabolic nature of senescent cells, and reveals a metabolic link between cellular senescence, lactate production, chronological aging and age-related pathologies including but not limited to cancer.
Cervical cancer screening for PLWHIV; experiences from an innovative cervical screening and treatment program in Nigeria
Authors: Ogunsola Olabanjo Okunlola , Ajayi Oluseye Ayodele , Ojo Temitope Olumuyiwa , Osayi Emmanuel , Wudiri Kucheli , Amoo Babatunde , Ayoka-Ikechukwu Rita , Olumeyan Olufemi , Ifechelobi Chukwuemeka , Okonkwo Prosper , Yewande Akinro
Published: January 2023

We evaluated cervical cancer program for women living with HIV (WLHIV) to determine program screening rate, primary case finder screening accuracy and treatment and post-treatment screening rate among screen-positive patients.
Methods
A one-year review of cervical cancer program data among WLHIV aged 15-49 years on HIV care across forty-one comprehensive ART sites supported by APIN (a PEPFAR implementing partner) in Nigeria was conducted from October 2020 to July 2021. Initial screening was done using visual inspection with acetic acid (VIA) followed by a gynaecologist expert review through a program-designed software named AVIVA, as a confirmatory test. Associations were measured between the primary case finder screening accuracy and study covariates at p-value of 0.05.
Results
About 10,289 asymptomatic women aged 15-49 years living with HIV were screened for cervical cancer by primary case finders using VIA-based screening test. 732 (7.1%) had a positive screening test suggestive of precancerous lesions or cervical cancer. 315 (43.0%) of VIA positive women had treatment using thermal ablation and less than one-third (21.6%) of those treated came back for post-treatment screening test. Primary case finder screening sensitivity, specificity, positive predictive and negative predictive accuracy using gynaecologist review as confirmatory test were 60.8%, 71.5%, 41.7% and 84.5% respectively. Overall screening accuracy was 68.8%.
Conclusion and Recommendation
This innovative approach to cervical cancer screening among WLHIV yielded modest results in preventing program error and wastages. Wider deployment of expert-based reviews of VIA though AVIVA software might be a veritable approach to improve screening accuracy in low resource settings.
Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
Authors: Mitsi Elena , Diniz Mariana , Reine Jesus , Collins Andrea , Robinson Ryan , Hyder-Wright Angela , Farrar Madlen , Liatsikos Konstantinos , Hamilton Josh , Onyema Onyia , Urban Britta , Solorzano Carla , Lambe Teresa , Draper Simon , Weiskopf Daniela , Sette Alessandro , Maini Mala , Ferreira Daniela
Published: January 2023

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.
Cascaded hard X-ray self-seeded free-electron laser at MHz-repetition-rate
Authors: Liu Shan , Grech Christian , Guetg Marc , Karabekyan Suren , Kocharyan Vitali , Kujala Naresh , Lechner Christoph , Long Tianyun , Mirian Najmeh , Qin Weilun , Serkez Svitozar , Tomin Sergey , Yan Jiawei , Abeghyan Suren , Anton Jayson , Blank Vladimir , Boesenberg Ukrike , Brinker Frank , Chen Ye , Decking Winfried , Dong Xiaohao , Kearney Steve , Civita Daniele La , Madsen Anders , Maltezopoulos Theophilos , Rodriguez-Fernandez Angel , Saldin Evgueni , Samoylova Liubov , Scholz Matthias , Sinn Harald , Sleziona Vivien , Shu Deming , Tanikawa Takanori , Terentyev Sergey , Trebushinin Andrei , Tschentscher Thomas , Vannoni Maurizio , Wohlenberg Torsten , Yakopov Mikhail , Geloni Gianluca
Published: January 2023

The European XFEL is currently the only high-repetition rate hard X-ray free electron laser (FEL) facility in operation worldwide. We significantly improved its capabilities by installing a cascaded Hard X-ray Self-Seeding (HXRSS) system, composed of two single-crystal monochromators. With this system, mJ-level pulses in the photon energy range of 6 -14keV with a bandwidth around 1eV (corresponding to about 1mJ/eV spectral density) were generated. Combined with the burst-mode, multi-MHz repetition rate of the European XFEL accelerator, the cascaded HXRSS setup provides two orders of magnitude higher average spectral brightness than any other FEL facility. At 2.25 MHz repetition rate and photon energies in the 6-7 keV range, we observed for the first time heat-load effects on the HXRSS crystals, substantially altering the spectra of subsequent X-ray pulses. Using the cascaded self-seeding scheme, we successfully reduced this effect to below detection level. These results open up exciting possibilities in a wide range of scientific fields, exploiting the extreme brightness and the narrow bandwidth of HXRSS pulses.
Evolutionary dynamics in spatial public goods games with environmental feedbacks
Authors: Ding Rui , Wang Xianjia , Zhao Jinhua , Gu Cuiling , Chen Wenman , Huang Xingjun
Published: January 2023

Conflicting interests between individuals and groups are always emphasized in collective actions towards goals such as resource sustainability and environmental protection. These social dilemmas can be modeled by public goods games and collective risk dilemmas. However, the reality is that multiple generations share a common pool of resources, which leads to a high cost of today’s overexploitation to the welfare on future generations. Therefore, such delayed effects generate a multigenerational conflict. By establishing the relationship between individual payoffs and regional environmental quality, we build a coupled social-ecological coevolutionary model. To study how cooperative behaviors spread in a public goods game with environmental feedbacks and which factors influence it, we explore the mechanisms behind certain phases and phase transitions by monitoring the spatial distribution of strategies and the environmental quality of all regions. Some counterintuitive results can be obtained. For example, sometimes the stronger the ability of cooperators to improve the environment, the lower the overall level of cooperation in the system, which is related to the invasion of cooperative clusters by defectors in the crack of clusters. Moreover, the destructive power of defection and the cost of cooperation have a more complex effect on the system.
Extension of the Projected Gradient and Armijo’s Rule Concepts for Solving Convex Nonlinear Multiobjective Optimization Problems
Authors: Appolinaire TOUGMA , SOMÉ Kounhinir , COMPAORÉ Abdoulaye
Published: January 2023

In this work, we propose a method for solving a boundary constraints multiobjective optimization problems. The algorithm combines the projected gradient with a modified version of the Armijo Rule and the weighted sum to find the best solutions. Under the assumption that the objective functions are differentiable and convex, the convergence to an optimal Pareto point is established. Furthermore, we have successfully solved test problems with which we have calculated some performance indicators related to the convergence and diversity of obtained solutions. All these results have allowed us to highlight effectiveness and efficiency of our method.
Time-Based Dynamic Changes Of Gene Expression In The Hypoxic T47D Cell Line Duration Of Hypoxia: RNA Sequencing Approach
Authors: Annisa Annisa , Purnomosari Dewajani
Published: January 2023

Background : Uncontrolled proliferation of tumor cells leads to hypoxia. Hypoxia can cause changes in hypoxia responsive genes transcriptions as an adaptation to limited oxygen. RNA sequencing in breast cancer cells is still varied and is known to change with the duration of treatment. The aim of this project was to compare the mRNA profiles between normoxia and hypoxia of T47D breast cancer cells using RNA-seq.
Methods : T47D breast cancer cell cultured under hypoxic conditions (0.5% oxygen) for 6, 24 and 48 h. RNA was extracted using the Qiagen allprep DNA/RNA/Protein Mini kit. Total RNA with RNA Integrity Number >7 will be sequenced to reveal gene expression profiles.
Results: 143,875,430 out of 169,314,448 reads (85%) were passed filtering. Of those, 26.684,288 reads (18.45%) are from 6 hours hypoxia, 29,178,225 reads (20.28%) from hypoxia 24 hours, 27,615,450 reads (19.19%) from hypoxia 48 hours. While 24,514,359 reads (17.94%) are from the normoxia group. During treatment, 23 genes were differentially expressed between groups; three genes are downregulated, and the rest are upregulated. Three genes (TAF1C, CD63, TM7SF2) were upregulated in the normoxia group, two genes (CYP1A1 and VCP) were upregulated in 6 hours of hypoxia. Two genes (NEBL and KDM3A) were upregulated in 24 hours hypoxia, while six genes (ERBB3, PIKP1, Ro60, ESRP1, KLF6, MKRN2) were upregulated in 48 hours hypoxia group.
Conclusion: Gene expression profiles between treatment and control group are different. Modulation of gene expression during hypoxia plays a role in glycolysis, proliferation, growth, and migration.
TNFR2 mediates pancreatic cancer proliferation, migration, and invasion via the NF‑κB signaling pathway
Authors: Gao Zetian , Zhang Qiubo , Chen Hang , Li Hong , Chen Jiayi , Kang Jingyu , Gao Hui , Yu Hang , Song Yufei , Zhang Xie
Published: January 2023

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2) contributes to the development and progression of several tumors. In this study, we investigated the clinicopathologic data and outcomes of pancreatic cancer patients and elucidated the molecular mechanisms of TNFR2.
Method: We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal (n = 171) and malignant (n = 179) pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting.
Results: TNFR2 was more highly expressed in PDAC cells and tissues than in controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion in vitro. Mechanistically, TNFR2 binds to TNF-ɑ and activates the NF-κB signaling pathway.
Conclusion: TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF‑κB signaling pathway. TNFR2 may become a therapeutic target.
Identifying high snakebite risk area under climate change: Implications for community education and antivenom distribution
Authors: Yousefi Masoud , Yousefkhani Saeed Hosseinian , Grünig Marc , Kafash Anooshe , Rajabizadeh Mahdi , Pouyani Eskandar Rastegar
Published: January 2023

Snakebite is a global health problem and yearly snakebites have been estimated up to 5 million leading to about 100,000 deaths each year. While those numbers are showing that snakebite is one of the largest risks from wildlife, little is known about venomous snake distribution, spatial variation in snakebite risk, potential changes in snakebite risk pattern due to climate change, and vulnerable human population. As a consequence, management and prevention of snakebite is hampered by this lack of information. Previous studies suggest that habitat suitability models are effective tools in predicting snakebite risk areas under current and future climate and identifying vulnerable human population. Here we used an ensemble approach of five different habitat suitability modeling algorithms for 10 medically important venomous snakes to quantify snakebite risk pattern, map snakebite hotspots, calculate community composition changes and changes in vulnerability to snakebite in Iran under current and future climate (years 2041–2070 and 2071–2100). We identified areas with high snakebite risk in Iran and showed that snakebite risk will increase in some parts of the country. We also found mountainous areas (Zagros, Alborz, Kopet-Dagh mountains) will experience highest changes in species composition. We underline that in order to improve snakebite management, areas which were identified with high snakebite risk in Iran need to be prioritized for the distribution of antivenom medication and awareness rising programs among vulnerable human population.
Residual Stress Analysis of TC4/Inconel718 Functionally Graded Material Produced by Laser Additive Manufacturing Based on Progressive Activation Element Method
Authors: Zhao Hongjian , Gao Chi , Wang Zihao , Wang Quanyi , Liu Changsheng , zhan yu
Published: January 2023

With the continuous development of preparation technology, laser additive manufacturing (LAM) has become one of the effective ways to manufacture functionally graded materials due to its unique layer-by-layer stacking technology. However, the repeated and repeated rapid heating and cooling processes in the manufacturing process will generate large residual stress inside the structure, resulting in the destruction of the structure. In this paper, based on a new finite element method called progressive activation element method (PAE), a thermomechanical coupling model for simulating the process of LAM is established, and the influence of laser power and composition ratio of transition layers on the residual stress of the overall structure is discussed. The results show that there is a positive correlation between the laser power and the residual stress. The PAE method is compared with the traditional “Model Change” method, and it is found that the PAE method has advantages in computational efficiency, especially when calculating the residual stress of functionally graded materials, the efficiency can be improved by about 1650%. When the TC4/Inconel718 functionally graded material is prepared experimentally, the optimal composition ratio of the transition layers is 8:2. This paper provides reference for the understanding and reasonable suppression of residual stress of functionally graded materials in LAM.