bluuebunny/crossref_metadata_2025 huggingface dataset:
THBS1, a fatty acid-related metabolic gene, can promote the development of laryngeal cancer
Authors: Ji Fei-Hong , Qiu Xin-Guang
Published: November 2022

Laryngeal cancer is the second most prevalent head and neck tumor and it is one of the most common malignancies of the upper respiratory tract. Fatty acid metabolism affects cancer cell biology in several ways, and alterations in fatty acid metabolism are characteristic of both tumorigenesis and metastasis. Despite advances in laryngeal cancer diagnosis and treatment over the years, there has been no significant improvement in survival or mortality. Studying the role of fatty acid metabolism-related genes in laryngeal cancer will facilitate our search for valuable biomarkers to guide prognostic management and treatment selection. We constructed a prognostic risk score model for fatty acid metabolism-related genes by downloading and analyzing laryngeal cancers from the TCGA and GEO databases. We predicted survival outcomes of laryngeal cancer patients using a prognostic risk score model of fatty acid metabolism-related genes and analyzed the resistance of laryngeal cancer in different individuals to multiple drugs. In addition, the relationship between the prognostic risk score model and cellular infiltration characteristics of the tumor microenvironment were investigated. Through the prognostic risk scoring model, the genes with risk-prompting effect and related to prognosis were screened out for further research. Through the study of gene expression levels in the TCGA database, we screened out 120 differentially expressed fatty acid metabolism genes. LASSO-Cox and Cox regression analyses identified nine genes associated with prognosis to construct a prognostic risk score model for genes related to fatty acid metabolism. Both TCGA and GEO confirmed that samples in the high-risk score group had a worse prognosis than those in the low-risk score group. We found significant differences between the high-risk and low-risk groups for 22 drugs (P < 0.05). In addition, we found differences in immune cell infiltration between the different risk score groups. Finally, through the risk assessment model, combined with multiple databases, THBS1, a high-risk and prognosis-related gene, was screened. We also found that THBS1 could promote the migration, invasion and proliferation of laryngeal cancer cells by constructing THBS1 knockout cell lines. In our study, we identified key fatty acid-related genes differentially expressed in laryngeal carcinoma that can be used to adequately predict prognosis using a comprehensive bioinformatic experimental approach. It was also found that THBS1, a high-risk and prognosis-related gene, may regulate the occurrence and development of laryngeal cancer through fatty acid metabolism, which has further helped us to explore the role of fatty acid metabolism genes in laryngeal cancer.
Residual levels and dietary intake risk assessment of 11 pesticides in apricots from different ecological planting regions in China
Authors: Yang Song , Xing Yujun , Liu Quanquan , Wang Hairong , Gu Aiguo , Wang Jinzheng , Xue Xiaomin , Chen Ru
Published: November 2022

The frequent and massive use of pesticides has led to pesticide residues in apricot, threatening food safety and human health. A reliable and simple modified QuEChERS method with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 11 pesticides in apricot. Method validation indicated that satisfied linearity (R2 ≥ 0.9959), accuracy (recoveries of 72–119%), sensitivity (limits of detection, 0.03–0.30 μg/kg; limits of quantification, 0.13–1.00 μg/kg), and precision (relative standard deviations ≤ 11.9%), and matrix effects were 0.89–1.13. Apricot samples from different ecological regions in China were collected and tested using the proposed methods. Monitoring results were used to assess the dietary intake risk of Chinese populations of different ages and genders. Dietary risk assessment revealed that the risk quotients were 0.003–1.184% for different gender and age groups in China, indicating none unacceptable public health risk for general population. This work was thus significant in developing a simpler, more efficient and economical analysis method and food safety risks of the 11 pesticides on apricot and facilitated the establishment of maximum residue limits.
Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2
Authors: Chen Xiang , Yang Peipei , Qiao Yue , Ye Fei , Wang Zhipeng , Xu Mengting , Han Xiaowang , Song Li , Wu Yuehong , Ou Wen-Bin
Published: November 2022

Mutations in isocitrate dehydrogenase (IDH) are frequently found in low-grade gliomas, secondary glioblastoma, chondrosarcoma, acute myeloid leukemias, and intrahepatic cholangiocarcinoma. However, the molecular mechanisms of how IDH2 mutations induce carcinogenesis remain unclear. Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability. Compared with wild-type IDH2, the R172 and R140 point mutations resulted in a decrease in IDH2 activity, ROS, and lactate levels and an increase in glucose and ATP levels under normal and hypoxic conditions, indicating that mutant IDH2 increases cell dependency on mitochondrial oxidative phosphorylation, and reduces glycolysis under hypoxia. Overexpression of most of IDH2 point mutants showed anti-proliferative effects in the 293T and BV2 cell lines by inhibition of PI3K/AKT signaling and cyclin D1 expression and/or induced the expression of TNF-α and IL-6. Furthermore, bortezomib treatment resulted in dramatic degradation of IDH2 mutants, including R140G, R140Q, R140W, R172S and R172K, whereas it had little impact on the expression of WT and other mutants (R172M, R172W, R172G, R172C and R172P). In addition, targeting HSP90 minimally affected the expression of mutated IDH2 due to a lack of interaction between HSP90 and IDH2. The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors.
Sex difference in effect of ankle landing biomechanics in sagittal plane on knee valgus moment during single-leg landing
Authors: Lee Jinkyu , Shin Choongsoo S.
Published: November 2022

Ankle landing strategies affects the biomechanical characteristics of the knee joint, especially knee frontal plane loading. However, no studies have investigated whether the association between ankle landing biomechanics in sagittal plane and the knee frontal plane loading differs between sexes. The purpose of this study was to examine whether there is a sex difference in the effect of ankle plantar flexion at the contact angle, ankle range of motion (ROM), and ankle plantar flexion moment on knee valgus loading during single-leg landing. Twenty-five females and twenty-four males performed a single-leg landing. Joint kinematics and kinetics of the lower extremities were measured. The relationship between ankle biomechanics in the sagittal plane (ankle plantar flexion angle at contact, ROM, and peak ankle plantar flexion moment) and peak knee valgus moment were analyzed. In males, the larger ankle plantarflexion angle at contact and ROM were significantly associated with lower peak knee valgus moment. In addition, in males only, a greater peak ankle plantar flexion moment was significantly associated with a lower peak knee valgus moment and greater peak ankle inversion moment. Altering ankle landing strategies in the sagittal plane during single-leg landing may reduce the knee valgus moment, which is one of risk factors for anterior cruciate ligament injury, in males only.
Quality of life questionnaires validate a remote approach to ophthalmic management of primary Sjögren’s syndrome
Authors: Greenan E. , Pilson Q. , Ní Gabhann-Dromgoole J. , Murphy C. C.
Published: November 2022

Those with underlying autoimmune conditions were met with unparalleled challenges and were disproportionately affected by the COVID-19 pandemic. As such, we aimed to measure the impact of the pandemic on symptoms and the health and vision related quality of life (HR-QoL, VR-QoL) in patients with Primary Sjögren's Syndrome (pSS). Nineteen (55.9%) participants returned questionnaires for analysis, (17 female and 2 male, 61.6 years ± 9.9). There was no significant change in participants HR-QoL or VR-QoL, indicating that those with pSS remained resilient with regard to their physical and mental health throughout the pandemic. Furthermore, QoL was maintained despite 73.7% of participants having had outpatient appointments cancelled, delayed or rescheduled. Participants reported a lower QoL and feeling tenser in the COV19-QoL (3.3 ± 1.4 and 3.2 ± 1.3) representing feelings of apprehension and stress felt amongst the general population since the pandemic. Overall, and in spite of the concern caused by the COVID-19 pandemic for patients with autoimmune diseases, the health and well-being of patients with pSS remained stable. These findings strongly support the use of validated HR and VR-QoL questionnaires as an adjunct to the telemedicine consultation when assessing patients with pSS, offering an alternative to face-to-face consultations in post-pandemic era.
Suppression of stacking-fault expansion in 4H-SiC PiN diodes using proton implantation to solve bipolar degradation
Authors: Kato Masashi , Watanabe Ohga , Mii Toshiki , Sakane Hitoshi , Harada Shunta
Published: November 2022

4H-SiC has been commercialized as a material for power semiconductor devices. However, the long-term reliability of 4H-SiC devices is a barrier to their widespread application, and the most important reliability issue in 4H-SiC devices is bipolar degradation. This degradation is caused by the expansion of single Shockley stacking-faults (1SSFs) from basal plane dislocations in the 4H-SiC crystal. Here, we present a method for suppressing the 1SSF expansion by proton implantation on a 4H-SiC epitaxial wafer. PiN diodes fabricated on a proton-implanted wafer show current–voltage characteristics similar to those of PiN diodes without proton implantation. In contrast, the expansion of 1SSFs is effectively suppressed in PiN diodes with proton implantation. Therefore, proton implantation into 4H-SiC epitaxial wafers is an effective method for suppressing bipolar degradation in 4H-SiC power-semiconductor devices while maintaining device performance. This result contributes to the development of highly reliable 4H-SiC devices.
Predicting the re-distribution of antibiotic molecules caused by inter-species interactions in microbial communities
Authors: Reding Carlos
Published: November 2022

Microbes associate in nature forming complex communities, but they are often studied in purified form. Here I show that neighbouring species enforce the re-distribution of carbon and antimicrobial molecules, predictably changing drug efficacy with respect to standard laboratory assays. A simple mathematical model, validated experimentally using pairwise competition assays, suggests that differences in drug sensitivity between the competing species causes the re-distribution of drug molecules without affecting carbon uptake. The re-distribution of drug is even when species have similar drug sensitivity, reducing drug efficacy. But when their sensitivities differ the re-distribution is uneven: The most sensitive species accumulates more drug molecules, increasing efficacy against it. Drug efficacy tests relying on samples with multiple species are considered unreliable and unpredictable, but study demonstrates that efficacy in these cases can be qualitatively predicted. It also suggests that living in communities can be beneficial even when all species compete for a single carbon source, as the relationship between cell density and drug required to inhibit their growth may be more complex than previously thought.
Sumanene-functionalised bis(terpyridine)–ruthenium(ii) complexes showing photoinduced structural change and cation sensing
Authors: Han Junyi , Yakiyama Yumi , Takeda Youhei , Sakurai Hidehiro
Published: November 2022

Ru(ii) complexes with sumanene-functionalised terpyridine ligands exhibited dual emission via the TICT mechanism due to the relatively easy rotation around the sumanene–terpyridine bond axis. They also showed selective Li+ sensing ability.
Understanding the ultraviolet, green, red, near infrared and infrared emission properties of bismuth halide double perovskite
Authors: Huang Anjun , Liu Mingzhe , Duan Chang-Kui , Wong Ka-Leung , Tanner Peter A.
Published: November 2022

Cs2NaBiCl6shows multi-luminescence properties at low temperature from the ultraviolet to infrared spectral regions, thereby demonstrating its potential application in the anti-counterfeiting field.
Regulation of excited-state properties of dibenzothiophene-based fluorophores for realizing efficient deep-blue and HLCT-sensitized OLEDs
Authors: Lv Jichen , Huo Yumiao , Xiao Shu , Zhao Zhennan , Peng Ling , Liu Yuchao , Ren Zhongjie , Ma Dongge , Ying Shian , Yan Shouke
Published: November 2022

High external quantum efficiencies of 7.08% and 27.30% and low efficiency roll-off are achieved simultaneously based on HLCT-sensitized fluorescent and phosphorescent OLEDs.
The switching decomposition pulse width modulation with reduced common mode voltage for reduced switch counts neutral point clamped inverter
Authors: Jing Mengmeng , Du Chunshui , Xing Xiangyang , Chen Zhiyuan , Wen Chuangping
Published: November 2022

Compared with a conventional three‐levelconverter, a reduced switch counts three‐level neutral point clamped (RSC‐3LNPC) inverter uses only 10 switching devices to achieve three‐leveloutput at a lower cost. However, in the RSC‐3LNPC inverter, the common modevoltage (CMV) reduction and neutral point voltage (NPV) balance are mutuallycoupled, and the buck switching module eliminates medium vectors, making conventional modulation methods no longer applicable. To address this problem, this paperdevelops a generation mechanism of the voltage and switching vectors for RSC‐3LNPC inverter and proposes a switching decomposition pulse width modulation (SDPWM) scheme. First, a virtual medium vector with two large vectors having the samedwell time is introduced. Then, the small and zero vectors with low CMV, along with the large and virtual medium vectors, are adopted, and by adjusting their dwell time, the NPV is balanced while reducing CMV. In addition, to reduce computational burden, the switching vector isdecomposed into a buck switching vector and a two‐level switching vector. Both switching vector sequences with transformed duty cycles are carefully designed to achieve only three switching transactions per switching period. Finally, validation and correctness of the proposed SDPWM scheme for RSC‐3LNPC inverterare verified by simulation and experiments.
A local flexibility market framework for exploiting DERs’ flexibility capabilities by a technical virtual power plant
Authors: Pourghaderi Niloofar , Fotuhi‐Firuzabad Mahmud , Moeini‐Aghtaie Moein , Kabirifar Milad , Dehghanian Payman
Published: November 2022

This paper presents a new intra‐day intra‐hourly local flexibility market (LFM) framework to exploit distributed energy resources’ (DERs) flexibility capabilities. A technical virtual power plant (TVPP) operates the LFM in which the DER aggregators participate. The TVPP offers the provided flexibility capabilities to wholesale flexibility market (WFM) as well as compensating the intra‐hourly variability in power distribution network. In the proposed framework, the TVPP clears the LFM by considering hierarchical transactions with the aggregator agents to find the market equilibrium in which the DERs’ flexibility capabilities are optimally exploited while all participating agents make profit by trading flexibility capabilities in the LFM. A bilevel optimization model with multiple lower levels is considered to address different agents’ preferences and transactions in the LFM. In the upper‐level problem, the TVPP aims at maximizing its profit while each lower‐level problem represents an aggregator agent's optimization problem. The proposed model is reformulated into a single‐level mixed integer linear programming problem and is implemented on the distribution network connected to Bus 5 of the Roy Billinton test system (RBTS) as well as a 119‐bus test system. The results demonstrate the effectiveness of the model to utilize DERs’ flexibility and provide revenue opportunities for different agents.
The first gradual solar energetic particle event with an enhanced 3He abundance on Solar Orbiter
Authors: Bučík R. , Mason G. M. , Gómez-Herrero R. , Krupar V. , Lario D. , Starkey M. J. , Ho G. C. , Rodríguez-Pacheco J. , Wimmer-Schweingruber R. F. , Espinosa Lara F. , Tadesse T. , Balmaceda L. , Cohen C. M. S. , Dayeh M. A. , Desai M. I. , Kühl P. , Nitta N. V. , Wiedenbeck M. E. , Xu Z. G.
Published: November 2022

The origin of 3He abundance enhancements in gradual solar energetic particle (SEP) events remains largely unexplained. Two mechanisms have been suggested: the reacceleration of remnant flare material by coronal mass ejection (CME)-driven shocks in interplanetary space, and concomitant activity in the corona. We explore the first gradual SEP event with enhanced 3He abundance that was observed by Solar Orbiter. The event started on 2020 November 24 and was associated with a relatively fast halo CME. During the event, the spacecraft was at 0.9 au from the Sun. The event-averaged 3He/4He abundance ratio is 24 times higher than the coronal or solar wind value, and the timing of the 3He intensity was similar to that of other species. We inspected available imaging, radio observations, and the spacecraft magnetic connection to the CME source. The most probable cause of the enhanced 3He abundance apparently are residual 3He ions remaining from a preceding long period of 3He-rich SEPs on 2020 November 17–23.
Pulmonale Sarkoidose
Authors: Bergner Raoul , Forst Yannick
Published: November 2022

Die Sarkoidose ist in Nordeuropa die häufigste granulomatöse Erkrankung. Sie kann prinzipiell nahezu alle Organe betreffen. Die Lunge ist jedoch mit 90–95 % das am häufigsten betroffene Organ. Die pulmonale Sarkoidose kann von einem asymptomatischen Befall bis hin zu einer interstitiellen Fibrose mit schwer eingeschränkter Lungenfunktion auftreten. Mit dem konventionellen Röntgen wird die pulmonale Sarkoidose in 4 Typen unterteilt. Neben der Lungenfunktion ist der radiologische Befallstyp mit entscheidend für die Therapieindikation. Wichtige Bausteine in der Diagnostik sind neben der radiologischen Bildgebung die Bestimmung der Lungenfunktion sowie die Bronchoskopie zur histologischen Diagnosesicherung. Daneben muss bei möglichem Multiorganbefall eine umfangreiche Organdiagnostik zur Erfassung weiterer Organmanifestationen erfolgen. Die Therapie besteht an erster Stelle aus der Gabe von Glukokortikoiden sowie bei unzureichender Wirkung oder Steroid-induzierten Nebenwirkungen aus der zusätzlichen Gabe von Immunsuppressiva. Hier steht an vorderster Stelle eine Therapie mit Methotrexat (MTX).
Interstitielle Lungenbeteiligung bei der rheumatoiden Arthritis
Authors: Klemm Philipp , Henes Jörg , Xanthouli Panagiota
Published: November 2022

Die RA-ILD ist eine schwerwiegende extraartikuläre Manifestation der RA, welche mit einer gesteigerten Mortalität einhergeht. Dieser Beitrag verschafft einen Überblick und greift neue Erkenntnisse zu diesem wichtigen Thema auf. Eingegangen wird auf Epidemiologie, Risikofaktoren, Prognose sowie auf Diagnostik und Therapie. Besonders wichtig sind die frühe Diagnose und die Evaluation der Risikofaktoren. Diese ermöglichen eine Prognoseabschätzung. Dabei spielt die HRCT-Morphologie der Lungen wie auch eine Mutation in MUC5B eine besondere Rolle. In der täglichen Praxis sollte Augenmerk auf Anamnese, körperliche Untersuchung und die regelmäßige Lungenfunktion gerichtet werden, um progredient fibrosierende Verläufe der RA-ILD frühzeitig zu entdecken. Für diese Verlaufsformen gibt es neben der Therapie mittlerweile auch die Option einer antifibrotischen Therapie.
Interstitial Pneumonia with Autoimmune Features (IPAF)
Authors: Gerber Alexander
Published: November 2022

Der Terminus Interstitial Pneumonia with Autoimmune Features (IPAF) wurde im Jahr 2015 samt entsprechender Klassifikationskriterien von einer interdisziplinären Task Force bestehend aus Mitgliedern der European Respiratory Society (ERS) und American Thoracic Society (ATS) vorgeschlagen. Das Akronym bezeichnet keine eigenständige Entität, sondern umschreibt ein heterogenes Patientenkollektiv mit idiopathischen interstitiellen Pneumonien und autoimmunen Eigenschaften. Für die Klassifikation einer interstitiellen Pneumonie als IPAF gilt: 3 Vorbedingungen und 2 von 3 Domänen (1. Klinische Domäne, 2. Serologische Domäne, 3. Morphologische Domäne) müssen erfüllt sein. Eine Domäne gilt als erfüllt, wenn mindestens ein Kriterium nachgewiesen wird (siehe Kasten „Klassifikationskriterien“). Die IPAF-Kriterien wurden geschaffen, um Patienten dieses Kollektivs für die weitere Erforschung in standardisierter Weise zu klassifizieren. Bislang gibt es jedoch sehr wenige prospektive IPAF-Beobachtungsstudien und die verschiedenen IPAF-Kohorten sind äußerst inhomogen. Sowohl die Klassifikation als auch die Betreuung von IPAF-Patienten erfordern eine interdisziplinäre klinische Zusammenarbeit zwischen Pneumologen und Rheumatologen.
Modeling the rheological behavior of crude oil–water emulsions
Authors: Papadimitriou Maria K. , Stephanou Pavlos S.
Published: November 2022

During crude oil extraction, crude oil is often mixed with water, leading to the formation of water-in-oil emulsions. Since these emulsions pose severe flow resistance, such as higher pressure drops, due to their complex fluid rheology, it is important to have in our arsenal a rheological constitutive model that accurately predicts their rheological response. In the present work, we propose such a model wherein the emulsions are modeled as deformable volume-preserving droplets via the use of a determinant-preserving contravariant second-rank tensor. We use the generalized bracket formalism of non-equilibrium thermodynamics to make sure that the derived model is by construction thermodynamically admissible. An additional scalar structural variable is considered to allow the prediction of a yielding point, following previous work. The predictions of the new model are shown to be in very good agreement with available experimental measurements.
Surface-charge-mobility-modulated electrokinetic energy conversion in graphene nanochannels
Authors: Liu Yongbo , Xing Jingnan , Pi Jiandong
Published: November 2022

In recent years, electrokinetic energy conversion for pressure-driven flow through hydrophobic nanochannels has attracted increasing attention from numerous researchers. However, the reported electrokinetic energy conversion efficiencies may be overestimated owing to neglect of the surface charge mobility effect of hydrophobic nanochannels. In fact, both the effective slip length and the induced streaming potential are influenced by the surface charge mobility. In this paper, a theoretical model for electrokinetic energy conversion through graphene nanochannels is developed with consideration of the influence of surface charge mobility. The surface charge density σs varies from very low to considerably high. A numerical solution to the electric potential is obtained by using the finite difference method. We also derive analytical solutions for two limiting cases, namely, the case with a low zeta potential and the case without considerable electric double layer overlap. Our results reveal that consideration of the surface charge mobility leads to a 44% reduction in the maximum conversion efficiency. The predicted maximum efficiency is approximately 5.9% at σs = −0.0162 C/m2. Our results may prove useful for predicting and optimizing the electrokinetic conversion efficiency in hydrophobic nanochannels.
Effects of spanwise length and side-wall boundary condition on plunging breaking waves
Authors: Jiang Peng , Huang Yichen , Xie Bin , Lin Zhiliang
Published: November 2022

A systematic study of the effect of the spanwise length and the sidewall boundary condition of a numerical wave flume (NWF) on direct numerical simulation of a plunging breaking wave is performed. To deal with the topological changes of free surfaces, a high-fidelity numerical model is employed to solve the Navier–Stokes equations together with the volume of fluid function. After verification by two-dimensional (2D) simulations of a plunging breaker on a sloping beach, ten NWFs with different spanwise extents and sidewall boundary conditions are studied. Special attention is devoted to the three-dimensionality of the plunging breaker. Compared with three-dimensional (3D) models, the 2D model accurately reproduces the dynamics of a breaking solitary wave in the early stage, but it is inadequate for the study of the post-breaking process. For a 3D NWF with nonslip sidewall boundary condition, the wave domain can be divided into two regions with different physical properties. In the near-wall region, the nonslip boundary condition on the sidewall plays a crucial role in the wave hydrodynamics, while in the central region, the properties of the breaking wave are similar to those for the periodic boundary condition, which provide a closer representation of the real sea environment. The spanwise length of the NWF plays only a minor role in simulations under the periodic boundary condition. Furthermore, lateral boundaries and spanwise length show more influences on a plunging breaker with larger incident wave steepness. This study provides valuable support for the design of numerical simulations of wave breaking.
Autoinflammatory manifestations in adult patients
Authors: Rodolfi Stefano , Nasone Irene , Folci Marco , Selmi Carlo , Brunetta Enrico
Published: November 2022

Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis, and elevation of acute phase reactants, in the absence of an identified infectious etiology, generally without detectable serum autoantibodies, with variable response to glucocorticoids and in some cases colchicine, which represented the mainstay of treatment until cytokine blockade therapies became available. The first autoinflammatory diseases to be described were monogenic disorders caused by missense mutations in inflammasome components and were recognized predominantly during childhood or early adulthood. However, the progress of genetic analyses and a more detailed immunological phenotyping capacity led to the discovery a wide spectrum of diseases, often becoming manifest or being diagnosed in the adult population. The beneficial role of targeting hyperinflammation via interleukin 1 in complex non-immune-mediated diseases is a field of growing clinical interest. We provide an overview of the autoinflammatory diseases of interest to physicians treating adult patients and to analyze the contribution of hyperinflammation in non-immune-mediated diseases; the result is intended to provide a roadmap to orient scientists and clinicians in this broad area.
Phenology and Voltinism of Emerald Ash Borer (Coleoptera: Buprestidae) in Central North Carolina
Authors: Bohannon G Ryan , Johnson Courtney L , Jetton Robert M , Oten Kelly L F
Published: November 2022

The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), has killed millions of ash (Fraxinus spp.) trees across North America. Classical biological control using introductions of parasitoid wasps may provide a sustainable approach to managing this invasive insect. However, the establishment of parasitoids in the southern United States has been difficult. The phenology of emerald ash borer was studied in central North Carolina to inform biological control efforts that better align with the seasonal availability of susceptible emerald ash borer life stages in the warm climate of this region. Biweekly emerald ash borer life stage assessments were conducted in stands of infested green ash (Fraxinus pennsylvanica Marshall, Lamiales: Oleaceae) over 26 consecutive months (June 2019 through August 2021). Adult trapping was also conducted in these stands in the spring and summer of 2019, 2020, and 2021. Based on these collections, emerald ash borer exhibits a univoltine (1-yr) life cycle. Parasitoid-susceptible larvae (third and fourth instars in galleries) are present from late June through October (~1,100–3,000 degree days base 10ºC) and are mostly absent during the remainder of the year. Parasitoid release timings and the life history of selected parasitoid species should be aligned with this window of host availability to be effective. This characterization of emerald ash borer phenology and voltinism will help improve the timing and effectiveness of management efforts as this forest pest continues to spread in southern North America.
Epigenetic Inheritance: Impact for Biology and Society—recent progress, current questions and future challenges
Authors: Arzate-Mejía Rodrigo G , Mansuy Isabelle M
Published: November 2022

Epigenetic inheritance has emerged as a new research discipline that aims to study the mechanisms underlying the transmission of acquired traits across generations. Such transmission is well established in plants and invertebrates but remains not well characterized and understood in mammals. Important questions are how life experiences and environmental factors induce phenotypic changes that are passed to the offspring of exposed individuals, sometimes across several successive generations, what is the contribution of germ cells and what are the consequences for health and disease. These questions were recently discussed at the symposium Epigenetic Inheritance: Impact for Biology and Society organized every 2 years in Zürich, Switzerland. This review provides a summary of the research presented during the symposium and discusses current important questions, perspectives and challenges for the field in the future.
The Mir Yeshiva’s Holocaust Experience: Ultra-Orthodox Perspectives on Japanese Wartime Attitudes towards Jewish Refugees
Authors: Kowner Rotem
Published: November 2022

The exodus of Jewish refugees from Lithuania to East Asia in late 1940 has become one of the most remarkable stories of rescue during the Holocaust. The largest group among these refugees was the Mir Yeshiva—one of Europe’s most notable Jewish educational institutions at the time, and the only Lithuanian yeshiva to survive the war in its entirety. Recent studies of this story have emphasized the role of the rescuers—particularly the Japanese vice consul Sugihara Chiune, who issued visas to the Jews—while neglecting the perspectives of the rescued. Nevertheless, the Mir Yeshiva has produced numerous accounts of its wartime ordeal over the past seventy years. Overlooked for the most part by the historiography of this period, the Mir testimonies and writings shed new light on the experiences of the Jewish refugees in Lithuania (1939–1940) and East Asia (1941–1945). Considering these accounts within their broader historical and international context, this article highlights their contribution to our understanding of this episode and Japanese wartime attitudes toward Jewish refugees.
Root-secreted (–)-loliolide modulates both belowground defense and aboveground flowering in Arabidopsis and tobacco
Authors: Li Feng-Li , Chen Xin , Luo Hui-Min , Meiners Scott J , Kong Chui-Hua
Published: November 2022

Plant defense, growth, and reproduction can be modulated by chemicals emitted from neighboring plants, mainly via volatile aboveground signals. However, belowground signals and their underlying control mechanisms are largely unknown. Here, we experimentally demonstrate that the root-secreted carotenoid (–)-loliolide mediates both defensive and reproductive responses in wild-type Arabidopsis, a carotenoid-deficient Arabidopsis mutant (szl1-1), and tobacco (Nicotiana benthamiana). Wild-type Arabidopsis plants flower later than szl1-1, and they secrete (–)-loliolide into the soil, whereas szl1-1 roots do not. When Arabidopsis and tobacco occur together, wild-type Arabidopsis induces nicotine production and defense-related gene expression in tobacco, whereas szl1-1 impairs this induction but accelerates tobacco flowering. Furthermore, nicotine production and the expression of the key genes involved in nicotine biosynthesis (QPT, PMT1), plant defense (CAT1, SOD1, PR-2a, PI-II, TPI), and flowering (AP1, LFY, SOC1, FT3, FLC) are differently regulated by incubation with wild-type Arabidopsis and szl1-1 root exudates or (–)-loliolide. In particular, (–)-loliolide up-regulated flowering suppressors (FT3 and FLC) and transiently down-regulated flowering stimulators (AP1 and SOC1), delaying tobacco flowering. Therefore, root-secreted (–)-loliolide modulates plant belowground defense and aboveground flowering, yielding critical insights into plant–plant signaling interactions.
Spectral analysis of ultra-cool white dwarfs polluted by planetary debris
Authors: Elms Abbigail K , Tremblay Pier-Emmanuel , Gänsicke Boris T , Koester Detlev , Hollands Mark A , Gentile Fusillo Nicola Pietro , Cunningham Tim , Apps Kevin
Published: November 2022

We identify two ultra-cool (${T_\mathrm{eff}}\lt 4000$ K) metal-polluted (DZ) white dwarfs WD J2147−4035 and WD J1922+0233 as the coolest and second coolest DZ stars known to date with ${T_\mathrm{eff}}\approx 3050$ K and ${T_\mathrm{eff}}\approx 3340$ K, respectively. Strong atmospheric collision-induced absorption (CIA) causes the suppression of red optical and infrared flux in WD J1922+0233, resulting in an unusually blue colour given its low temperature. WD J2147−4035 has moderate infrared CIA yet has the reddest optical colours known for a DZ white dwarf. Microphysics improvements to the non-ideal effects and CIA opacities in our model atmosphere code yields reasonable solutions to observations of these ultra-cool stars. WD J2147−4035 has a cooling age of over 10 Gyr which is the largest known for a DZ white dwarf, whereas WD J1922+0233 is slightly younger with a cooling age of 9 Gyr. Galactic kinematics calculations from precise Gaia EDR3 astrometry reveal these ultra-cool DZ stars as likely members of the Galactic disc thus they could be pivotal objects in future studies constraining an upper age limit for the disc of the Milky Way. We present intermediate-resolution spectroscopy for both objects, which provides the first spectroscopic observations of WD J2147−4035. Detections of sodium and potassium are made in both white dwarfs, in addition to calcium in WD J1922+0233 and lithium in WD J2147−4035. We identify the magnetic nature of WD J2147−4035 from Zeeman splitting in the lithium line and also make a tentative detection of carbon, so we classify this star as DZQH. WD J1922+0233 likely accreted planetary crust debris, while the debris composition that polluted WD J2147−4035 remains unconstrained.
Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy
Authors: Allen Barrett D , Alaghband Yasaman , Kramár Eniko A , Ru Ning , Petit Benoit , Grilj Veljko , Petronek Michael S , Pulliam Casey F , Kim Rachel Y , Doan Ngoc-Lien , Baulch Janet E , Wood Marcelo A , Bailat Claude , Spitz Douglas R , Vozenin Marie-Catherine , Limoli Charles L
Published: November 2022

Background

Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes.

Methods

Cohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment. Animals were sacrificed 6 months post-irradiation and tissues were analyzed for neurological and cerebrovascular decrements.

Results

The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neurocognitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin), and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and the preservation of the cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels.

Conclusions

Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlights its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefits of FLASH-RT that extend from synapse to cognition and the microvasculature.
Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative study: A systematic review and meta-analysis
Authors: Tsang Tim K. , Sullivan Sheena G. , Huang Xiaotong , Wang Can , Wang Yifan , Nealon Joshua , Yang Bingyi , Ainslie Kylie E. C. , Cowling Benjamin J.
Published: November 2022

Background

Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. In settings with high pre-existing immunity, vaccine effectiveness (VE) should decrease with higher levels of immunity among unvaccinated individuals. Here, we conducted a systematic review and meta-analysis to understand the influence of prior infection on VE.

Methods

We included test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. To determine the impact of prior infections on VE estimates, we compared studies that excluded or included people with prior COVID-19 infection. We also compared VE estimates by the cumulative incidence of cases before the start of and incidence rates during each study in the study locations, as further measures of prior infections in the community.

Findings

We identified 67 studies that met inclusion criteria. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between the cumulative incidence of cases before the start of the study and VE estimates against infection (spearman correlation (ρ) = −0.32; 95% CI: −0.45, −0.18) and severe disease (ρ= −0.49; 95% CI: −0.64, −0.30). There was also a negative correlation between the incidence rates of cases during the study period and VE estimates against infection (ρ= - 0.48; 95% CI: −0.59, −0.34) and severe disease (ρ= −0.42; 95% CI: −0.58, −0.23).

Interpretation

Based on a review of published VE estimates we found clear empirical evidence that higher levels of pre-existing immunity in a population were associated with lower VE estimates. Excluding previously infected individuals from VE studies may result in higher VE estimates with limited generalisability to the wider population. Prior infections should be treated as confounder and effect modificatory when the policies were targeted to whole population or stratified by infection history, respectively.
Cryo-electron microscopy of the f1 filamentous phage reveals a new paradigm in viral infection and assembly
Authors: Conners Rebecca , León-Quezada Rayén Ignacia , McLaren Mathew , Bennett Nicholas J , Daum Bertram , Rakonjac Jasna , Gold Vicki A M
Published: November 2022

Phages are viruses that infect bacteria and dominate every ecosystem on our planet. As well as impacting microbial ecology, physiology and evolution, phages are exploited as tools in molecular biology and biotechnology. This is particularly true for the Ff (f1, fd or M13) phages, which represent a widely distributed group of filamentous viruses. Over nearly five decades, Ff has seen an extraordinary range of applications, including in phage display and nanotechnology. However, the complete structure of the phage capsid and consequently the mechanisms of infection and assembly remain largely mysterious. Using cryo-electron microscopy and a highly efficient system for production of short Ff-derived nanorods, we have determined the first structure of a filamentous virus, including the filament tips. Structure combined with mutagenesis was employed to identify domains of the phage that are important in bacterial attack and for release of new phage progeny. These data allow new models to be proposed for the phage lifecycle and will undoubtedly enable the development of novel biotechnological applications.
A CMOS-based highly scalable flexible neural electrode interface
Authors: Zhao Eric T. , Hull Jacob , Hemed Nofar Mintz , Uluşan Hasan , Bartram Julian , Zhang Anqi , Wang Pingyu , Pham Albert , Ronchi Silvia , Huguenard John R. , Hierlemann Andreas , Melosh Nicholas A.
Published: November 2022

Perception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. Using thin film electrocorticography (ECoG) arrays, this cortical activity has been used to decode speech and individual finger movements, enabling neuroprosthetics, and to localize epileptic foci. However, the connectorization of these multi-thousand channel thin-film arrays to external circuitry is challenging; current state-of-the-art methods are complex, bulky, and unscalable. We address this shortcoming by developing an electrode connector based on an ultra-conformable thin film electrode array that self-assembles onto hard silicon chip sensors, such as microelectrode arrays (MEAs) or camera sensors enabling large channel counts at high density. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed flex2chip. Capillary-assisted assembly drives the pads to deform towards the chip surface, and van der Waals forces maintain this deformation, establishing mechanical and Ohmic contact onto individual pixels. We demonstrate a 2200-channel array with a channel density of 272 channels / mm2connected to the MEA through the flex2chip interconnection method. Thin film electrode arrays connected through the flex2chip successfully measured extracellular action potentials ex vivo. Furthermore, in a transgenic mouse model for absence epilepsy,Scn8a+/-, we observed highly variable propagation trajectories at micrometer scales, even across the duration of a single spike- and-wave discharge (SWD).
Target-distractor competition modulates saccade trajectories in space and object-space
Authors: Giuricich Caroline , Green Robert J. , Jordan Heather , Fallah Mazyar
Published: November 2022

Saccade planning and execution can be affected by a multitude of factors present in a target selection task. Recent studies have shown that the similarity between a target and nearby distractors affects the curvature of saccade trajectories, due to target-distractor competition. To further understand the nature of this competition, we varied the distance between and the similarity of complex target and distractor objects in a delayed match-to-sample task to examine their effects on saccade trajectories and better understand the underlying neural circuitry. For trials with short saccadic reaction times (SRTs) when target-distractor competition is still active, we found a robust effect of distance consistent with saccade vector averaging, whereas the effect of similarity suggested the existence of an object-based suppressive surround. At longer SRTs there was sufficient time for competition between the objects to complete and the distractor to be inhibited, which resulted in saccade trajectory deviations exhibiting the effects of a spatial suppressive surround. In terms of similarity, as the target-distractor similarity decreased, the initial saccade angle shifted towards the target, reflecting stronger distractor inhibition. There were no interactions between distance and similarity at any point in the time-course of target-distractor competition. Taken together, saccade trajectories reflect target-distractor competition that is affected independently by both spatial and object-space suppressive surrounds. The differences in saccade trajectories at short and long SRTs distinguish between active and completed decision-making processes. Thus, saccade responses are more beneficial than manual responses in studies of decision-making models.

Significance Statement

This is the first study to determine that the distance and similarity between visual objects independently affect saccade trajectories driven by the target-distractor competition process. Thus, spatiotemporal and object identity factors separately feed into saccade planning and execution, resulting in modulations of saccade trajectory metrics which are based on spatial and object-space suppressive surround mechanisms. Furthermore, this modulation of trajectory metrics distinguishes between active and complete decision-making processes. The findings are important for understanding the dynamic networks guiding target selection and are relevant for further development of decision-making models, as well as eye-tracking applications in health and disease.
gMCStool: automated network-based tool to search for metabolic vulnerabilities in cancer
Authors: Valcárcel Luis V. , José-Enériz Edurne San , Ordoñez Raquel , Apaolaza Iñigo , Valcárcel Ana , Garate Leire , San Miguel Jesús , Pineda-Lucena Antonio , Agirre Xabier , Prósper Felipe , Planes Francisco J.
Published: November 2022

The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we presentgMCStool, a freely accessible and online tool that allows us to carry out this task in a simple, efficient and intuitive environment.gMCStoolexploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of thousands of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. Based on RNA-seq data,gMCStoolextends and improves our previously developed algorithms to predict, visualize and analyze metabolic essential genes in cancer, demonstrating a superior performance than competing algorithms in both accuracy and computational performance. A detailed illustration ofgMCStoolis presented for multiple myeloma (MM), an incurable hematological malignancy. gMCStool could identify a synthetic lethal that explains the dependency on CTP Synthase 1 (CTPS1) in a sub-group of MM patients. We providein vitroexperimental evidence that supports this hypothesis, which opens a new research area to treat MM.