bluuebunny/crossref_metadata_2025 huggingface dataset:
Interim FDG-PET analysis to identify patients with aggressive non-Hodgkin lymphoma who benefit from treatment intensification: a post-hoc analysis of the PETAL trial
Authors: Seifert Robert , Kersting David , Rischpler Christoph , Sandach Patrick , Ferdinandus Justin , Fendler Wolfgang P. , Rahbar Kambiz , Weckesser Matthias , Umutlu Lale , Hanoun Christine , Hüttmann Andreas , Reinhardt Hans Christian , von Tresckow Bastian , Herrmann Ken , Dührsen Ulrich , Schäfers Michael
Published: October 2022

The randomized PETAL trial failed to demonstrate a benefit of interim FDG-PET (iPET)-based treatment intensification over continued standard therapy with CHOP (plus rituximab (R) in CD20-positive lymphomas). We hypothesized that PET analysis of all lymphoma manifestations may identify patients who benefitted from treatment intensification. A previously developed neural network was employed for iPET analysis to identify the highest pathological FDG uptake (max-SUVAI) and the mean FDG uptake of all lymphoma manifestations (mean-SUVAI). High mean-SUVAI uptake was determined separately for iPET-positive and iPET-negative patients. The endpoint was time-to-progression (TTP). There was a significant interaction of additional rituximab and mean-SUVAI in the iPET-negative group (HR = 0.6, p < 0.05). Patients with high mean-SUVAI had significantly prolonged TTP when treated with 6xR-CHOP + 2 R (not reached versus 52 months, p < 0.05), whereas max-SUVmanual failed to show an impact of additional rituximab. In the iPET-positive group, patients with high mean-SUVAI had a significantly longer TTP with (R-)CHOP than with the Burkitt protocol (14 versus 4 months, p < 0.01). Comprehensive iPET evaluation may provide new prognosticators in aggressive lymphoma. Additional application of rituximab was associated with prolonged TTP in iPET-negative patients with high mean-SUVAI. Comprehensive iPET interpretation could identify high-risk patients who benefit from study-specific interventions.
Electrically pumped quantum-dot lasers grown on 300 mm patterned Si photonic wafers
Authors: Shang Chen , Feng Kaiyin , Hughes Eamonn T. , Clark Andrew , Debnath Mukul , Koscica Rosalyn , Leake Gerald , Herman Joshua , Harame David , Ludewig Peter , Wan Yating , Bowers John E.
Published: October 2022

Monolithic integration of quantum dot (QD) gain materials onto Si photonic platforms via direct epitaxial growth is a promising solution for on-chip light sources. Recent developments have demonstrated superior device reliability in blanket hetero-epitaxy of III–V devices on Si at elevated temperatures. Yet, thick, defect management epi designs prevent vertical light coupling from the gain region to the Si-on-Insulator waveguides. Here, we demonstrate the first electrically pumped QD lasers grown by molecular beam epitaxy on a 300 mm patterned (001) Si wafer with a butt-coupled configuration. Unique growth and fabrication challenges imposed by the template architecture have been resolved, contributing to continuous wave lasing to 60 °C and a maximum double-side output power of 126.6 mW at 20 °C with a double-side wall-plug efficiency of 8.6%. The potential for robust on-chip laser operation and efficient low-loss light coupling to Si photonic circuits makes this heteroepitaxial integration platform on Si promising for scalable and low-cost mass production.
Electrodynamics of MnBi2Te4 intrinsic magnetic topological insulators
Authors: Tomarchio Luca , Mosesso Lorenzo , Macis Salvatore , Grilli Antonio , Romani Martina , Guidi Mariangela Cestelli , Zhu Kejing , Feng Xiao , Zacchigna Michele , Petrarca Massimo , He Ke , Lupi Stefano
Published: October 2022

We report on the electrodynamics of MnBi2Te4 thin films, an intrinsic magnetic topological material. We study its optical conductivity from terahertz (THz) to ultraviolet (UV) frequencies as a function of the film thickness, highlighting the presence of surface topological states superimposed on the bulk electrodynamics response. For the thinnest film, where the charge transport is dominated by Dirac surface states, we investigate the effect of the phase transition from the high-temperature topological protected state to the low-temperature magnetic (time-reversal broken) state by measuring the optical conductivity across the Néel temperature. At low temperatures, the breaking of the time reversal symmetry affects the optical conductivity, indicating that a magnetic-induced gap opens below TN.
Tuning the light emission of a Si micropillar quantum dot light-emitting device array with the strain coupling effect
Authors: Mo Yepei , Feng Xiaolong , Zhang Li , Han Renhou , Bao Rongrong , Pan Caofeng
Published: October 2022

Using an optical signal to realize sensing of a strain signal is a promising application for tactile sensors. However, most research is now focused on piezophototronic LED arrays, which are difficult to incorporate into the Si-based semiconductor industry. Due to the poor photoelectric performance of Si-based devices caused by the indirect band gap of Si, it has always been challenging to construct high density light-emitting devices with Si. Here, a Si-based quantum dot light-emitting device (QLED) array composed of p-Si micropillars is designed and fabricated, and the mechanism for modulation of the strain coupling effect in Si on the electroluminescence performance of Si-based QLEDs is studied. The introduction of QDs easily provides efficient and adjustable light emission and meets the requirements of different practical applications. The emission intensity of the QLED depends on the injected current density, and the transportation processes of the carriers can be modulated by the strain coupling effect. The combination of Si-based photonic devices with pressure sensing may have a significant impact on the fields of electronic skin and human‒machine interfaces. More importantly, this technology is fully compatible with the dominant Si-based semiconductor industry. Therefore, it shows promise in realizing the integration of large-scale Si-based photonic devices and expanding their application fields.
Retinal arterial tortuosity in Ehlers–Danlos syndromes
Authors: Ghoraba Hashem H. , Moshfeghi Darius M.
Published: October 2022

Purpose

To report a novel finding of retinal arterial tortuosity (RAT) associated with Ehlers–Danlos syndromes (EDS).

Methods

We queried the STAnford Research Repository (STARR) database to identify patients diagnosed with EDS. We included patients with a confirmed diagnosis of any subtype of EDS who had any form of readable retinal imaging including colour fundus photos, autofluorescence, red-free photos, red-free optical coherence tomography photos and fluorescein angiography. Patients who had no retinal imaging and those with no confirmed EDS diagnosis were excluded. Retinal images were reviewed for RAT and were graded into no, possible and definite RAT. Eyes with definite RAT were further graded into mild, moderate and severe. Eyes with definite RAT were again subclassified according to the type of involved vessels into first-order arteriolar, macular and arteriovenous.

Results

A total of 307 patients were identified using the STARR tool and 142 patients were included. Mean age was 40.9 ± 18.1 years and 87% were female. Underlying EDS subtypes were hypermobile EDS (69.7%), classical EDS (2.8%), vascular EDS (2.1%), myopathic EDS (0.7%) and not specified (24.6%). We graded 37.3% of patients with definite RAT, 10.6% with possible RAT and 52.1% with no RAT. In patients with definite RAT, we graded 39.2% of eyes with mild RAT, 40.2% with moderate RAT and 20.6% with severe RAT. In all, 84.9% showed involvement of first-order retinal arterioles, 35.8% showed involvement of macular arterioles and 1.9% showed arteriovenous involvement.

Conclusions

Variable degrees of RAT are associated with EDS.
Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system
Authors: Weigert Andreas , Zheng Xiang , Nenzel Alina , Turkowski Kati , Günther Stefan , Strack Elisabeth , Sirait-Fischer Evelyn , Elwakeel Eiman , Kur Ivan M. , Nikam Vandana S. , Valasarajan Chanil , Winter Hauke , Wissgott Alexander , Voswinkel Robert , Grimminger Friedrich , Brüne Bernhard , Seeger Werner , Pullamsetti Soni Savai , Savai Rajkumar
Published: October 2022

Fibrocytes are bone marrow–derived monocytic cells implicated in wound healing. Here, we identify their role in lung cancer progression/ metastasis. Selective manipulation of fibrocytes in mouse lung tumor models documents the central role of fibrocytes in boosting niche features and enhancing metastasis. Importantly, lung cancer patients show increased number of circulating fibrocytes and marked fibrocyte accumulation in the cancer niche. Using double and triple co-culture systems with human lung cancer cells, fibrocytes, macrophages and endothelial cells, we substantiate the central features of cancer-supporting niche: enhanced cancer cell proliferation and migration, macrophage activation, augmented endothelial cell sprouting and fibrocyte maturation. Upregulation of endothelin and its receptors are noted, and dual endothelin receptor blockade suppresses all cancer-supportive phenotypic alterations via acting on fibrocyte interaction with the cancer niche. We thus provide evidence for a crucial role of fibrocytes in lung cancer progression and metastasis, suggesting targets for treatment strategies.
Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy
Authors: Isser Ariel , Silver Aliyah B. , Pruitt Hawley C. , Mass Michal , Elias Emma H. , Aihara Gohta , Kang Si-Sim , Bachmann Niklas , Chen Ying-Yu , Leonard Elissa K. , Bieler Joan G. , Chaisawangwong Worarat , Choy Joseph , Shannon Sydney R. , Gerecht Sharon , Weber Jeffrey S. , Spangler Jamie B. , Schneck Jonathan P.
Published: October 2022

Helper (CD4+) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8+) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4+T cells hinders consistency and scalability of CD4+ T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4+ T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules. When combined with soluble co-stimulation signals, MHC II artificial APCs (aAPCs) expand cognate murine CD4+T cells, including rare endogenous subsets, to induce potent effector functions in vitro and in vivo. Moreover, MHC II aAPCs provide help signals that enhance antitumor function of aAPC-activated CD8+T cells in a mouse tumor model. Lastly, human leukocyte antigen class II-based aAPCs expand rare subsets of functional, antigen-specific human CD4+T cells. Overall, MHC II aAPCs provide a promising approach for harnessing targeted CD4+ T cell responses.
Ion transfer mechanisms in Mrp-type antiporters from high resolution cryoEM and molecular dynamics simulations
Authors: Lee Yongchan , Haapanen Outi , Altmeyer Anton , Kühlbrandt Werner , Sharma Vivek , Zickermann Volker
Published: October 2022

Multiple resistance and pH adaptation (Mrp) cation/proton antiporters are essential for growth of a variety of halophilic and alkaliphilic bacteria under stress conditions. Mrp-type antiporters are closely related to the membrane domain of respiratory complex I. We determined the structure of the Mrp antiporter from Bacillus pseudofirmus by electron cryo-microscopy at 2.2 Å resolution. The structure resolves more than 99% of the sidechains of the seven membrane subunits MrpA to MrpG plus 360 water molecules, including ~70 in putative ion translocation pathways. Molecular dynamics simulations based on the high-resolution structure revealed details of the antiport mechanism. We find that switching the position of a histidine residue between three hydrated pathways in the MrpA subunit is critical for proton transfer that drives gated trans-membrane sodium translocation. Several lines of evidence indicate that the same histidine-switch mechanism operates in respiratory complex I.
DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia
Authors: Nickels Eric M. , Li Shaobo , Myint Swe Swe , Arroyo Katti , Feng Qianxi , Siegmund Kimberly D. , de Smith Adam J. , Wiemels Joseph L.
Published: October 2022

Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown. Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence. Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia. We identify a significant negative coefficient bias, indicating DNA hypomethylation in cases, across the array and enhanced in open sea, shelf/shore, and gene body regions compared to promoter and CpG island regions. Here, we show an association between global DNA hypomethylation and future development of pediatric acute lymphoblastic leukemia across disease-discordant genetically identical twins, implying DNA hypomethylation may contribute more generally to leukemia risk.
Attenuating metal-substrate conjugation in atomically dispersed nickel catalysts for electroreduction of CO2 to CO
Authors: Wang Qiyou , Liu Kang , Hu Kangman , Cai Chao , Li Huangjingwei , Li Hongmei , Herran Matias , Lu Ying-Rui , Chan Ting-Shan , Ma Chao , Fu Junwei , Zhang Shiguo , Liang Ying , Cortés Emiliano , Liu Min
Published: October 2022

Atomically dispersed transition metals on carbon-based aromatic substrates are an emerging class of electrocatalysts for the electroreduction of CO2. However, electron delocalization of the metal site with the carbon support via d-π conjugation strongly hinders CO2activation at the active metal centers. Herein, we introduce a strategy to attenuate the d-π conjugation at single Ni atomic sites by functionalizing the support with cyano moieties. In situ attenuated total reflection infrared spectroscopy and theoretical calculations demonstrate that this strategy increases the electron density around the metal centers and facilitates CO2activation. As a result, for the electroreduction of CO2to CO in aqueous KHCO3electrolyte, the cyano-modified catalyst exhibits a turnover frequency of ~22,000 per hour at −1.178 V versus the reversible hydrogen electrode (RHE) and maintains a Faradaic efficiency (FE) above 90% even with a CO2concentration of only 30% in an H-type cell. In a flow cell under pure CO2at −0.93 V versus RHE the cyano-modified catalyst enables a current density of −300 mA/cm2with a FE above 90%.
Structure of the core human NADPH oxidase NOX2
Authors: Noreng Sigrid , Ota Naruhisa , Sun Yonglian , Ho Hoangdung , Johnson Matthew , Arthur Christopher P. , Schneider Kellen , Lehoux Isabelle , Davies Christopher W. , Mortara Kyle , Wong Kit , Seshasayee Dhaya , Masureel Matthieu , Payandeh Jian , Yi Tangsheng , Koerber James T.
Published: October 2022

NOX2 is the prototypical member of the NADPH oxidase NOX superfamily and produces superoxide (O2•−), a key reactive oxygen species (ROS) that is essential in innate and adaptive immunity. Mutations that lead to deficiency in NOX2 activity correlate with increased susceptibility to bacterial and fungal infections, resulting in chronic granulomatous disease. The core of NOX2 is formed by a heterodimeric transmembrane complex composed of NOX2 (formerly gp91) and p22, but a detailed description of its structural architecture is lacking. Here, we present the structure of the human NOX2 core complex bound to a selective anti-NOX2 antibody fragment. The core complex reveals an intricate extracellular topology of NOX2, a four-transmembrane fold of the p22 subunit, and an extensive transmembrane interface which provides insights into NOX2 assembly and activation. Functional assays uncover an inhibitory activity of the 7G5 antibody mediated by internalization-dependent and internalization-independent mechanisms. Overall, our results provide insights into the NOX2 core complex architecture, disease-causing mutations, and potential avenues for selective NOX2 pharmacological modulation.
Opposing functions of circadian protein DBP and atypical E2F family E2F8 in anti-tumor Th9 cell differentiation
Authors: Park Sang-A , Lim Yun-Ji , Ku Wai Lim , Zhang Dunfang , Cui Kairong , Tang Liu-Ya , Chia Cheryl , Zanvit Peter , Chen Zuojia , Jin Wenwen , Wang Dandan , Xu Junji , Liu Ousheng , Wang Fu , Cain Alexander , Guo Nancy , Nakatsukasa Hiroko , Wu Chuan , Zhang Ying E. , Zhao Keji , Chen WanJun
Published: October 2022

Interleukin-9 (IL-9)-producing CD4+T helper cells (Th9) have been implicated in allergy/asthma and anti-tumor immunity, yet molecular insights on their differentiation from activated T cells, driven by IL-4 and transforming growth factor-beta (TGF-β), is still lacking. Here we show opposing functions of two transcription factors, D-binding protein (DBP) and E2F8, in controlling Th9 differentiation. Specifically, TGF-β and IL-4 signaling induces phosphorylation of the serine 213 site in the linker region of the Smad3 (pSmad3L-Ser213) via phosphorylated p38, which is necessary and sufficient forIl9gene transcription. We identify DBP and E2F8 as an activator and repressor, respectively, forIl9transcription by pSmad3L-Ser213. Notably, Th9 cells with siRNA-mediated knockdown forDbporE2f8promote and suppress tumor growth, respectively, in mouse tumor models. Importantly, DBP and E2F8 also exhibit opposing functions in regulating human TH9 differentiation in vitro. Thus, our data uncover a molecular mechanism of Smad3 linker region-mediated, opposing functions of DBP and E2F8 in Th9 differentiation.
The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement
Authors: Brinkhaus Maximilian , Pannecoucke Erwin , van der Kooi Elvera J. , Bentlage Arthur E. H. , Derksen Ninotska I. L. , Andries Julie , Balbino Bianca , Sips Magdalena , Ulrichts Peter , Verheesen Peter , de Haard Hans , Rispens Theo , Savvides Savvas N. , Vidarsson Gestur
Published: October 2022

Binding to the neonatal Fc receptor (FcRn) extends serum half-life of IgG, and antagonizing this interaction is a promising therapeutic approach in IgG-mediated autoimmune diseases. Fc-MST-HN, designed for enhanced FcRn binding capacity, has not been evaluated in the context of a full-length antibody, and the structural properties of the attached Fab regions might affect the FcRn-mediated intracellular trafficking pathway. Here we present a comprehensive comparative analysis of the IgG salvage pathway between two full-size IgG1 variants, containing wild type and MST-HN Fc fragments, and their Fc-only counterparts. We find no evidence of Fab-regions affecting FcRn binding in cell-free assays, however, cellular assays show impaired binding of full-size IgG to FcRn, which translates into improved intracellular FcRn occupancy and intracellular accumulation of Fc-MST-HN compared to full size IgG1-MST-HN. The crystal structure of Fc-MST-HN in complex with FcRn provides a plausible explanation why the Fab disrupts the interaction only in the context of membrane-associated FcRn. Importantly, we find that Fc-MST-HN outperforms full-size IgG1-MST-HN in reducing IgG levels in cynomolgus monkeys. Collectively, our findings identify the cellular membrane context as a critical factor in FcRn biology and therapeutic targeting.
Evolution of defect structures leading to high ZT in GeTe-based thermoelectric materials
Authors: Jiang Yilin , Dong Jinfeng , Zhuang Hua-Lu , Yu Jincheng , Su Bin , Li Hezhang , Pei Jun , Sun Fu-Hua , Zhou Min , Hu Haihua , Li Jing-Wei , Han Zhanran , Zhang Bo-Ping , Mori Takao , Li Jing-Feng
Published: October 2022

GeTe is a promising mid-temperature thermoelectric compound but inevitably contains excessive Ge vacancies hindering its performance maximization. This work reveals that significant enhancement in the dimensionless figure of merit (ZT) could be realized by defect structure engineering from point defects to line and plane defects of Ge vacancies. The evolved defects including dislocations and nanodomains enhance phonon scattering to reduce lattice thermal conductivity in GeTe. The accumulation of cationic vacancies toward the formation of dislocations and planar defects weakens the scattering against electronic carriers, securing the carrier mobility and power factor. This synergistic effect on electronic and thermal transport properties remarkably increases the quality factor. As a result, a maximum ZT > 2.3 at 648 K and a record-high average ZT (300-798 K) were obtained for Bi0.07Ge0.90Te in lead-free GeTe-based compounds. This work demonstrates an important strategy for maximizing the thermoelectric performance of GeTe-based materials by engineering the defect structures, which could also be applied to other thermoelectric materials.
Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling
Authors: Sakaguchi Masaji , Okagawa Shota , Okubo Yuma , Otsuka Yuri , Fukuda Kazuki , Igata Motoyuki , Kondo Tatsuya , Sato Yoshifumi , Yoshizawa Tatsuya , Fukuda Takaichi , Yamagata Kazuya , Cai Weikang , Tseng Yu-Hua , Sakaguchi Nobuo , Kahn C. Ronald , Araki Eiichi
Published: October 2022

Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase 2A (PP2A) in insulin action/resistance in adipocytes. Unexpectedly, adipocyte-specific inactivation of α4 impairs insulin-induced Akt-mediated serine/threonine phosphorylation despite a decrease in the protein phosphatase 2A (PP2A) levels. Interestingly, loss of α4 also reduces insulin-induced insulin receptor tyrosine phosphorylation. This occurs through decreased association of α4 with Y-box protein 1, resulting in the enhancement of the tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, adipocyte-specific knockout of α4 in male mice results in impaired adipogenesis and altered mitochondrial oxidation leading to increased inflammation, systemic insulin resistance, hepatosteatosis, islet hyperplasia, and impaired thermogenesis. Thus, the α4 /Y-box protein 1(YBX1)-mediated pathway of insulin receptor signaling is involved in maintaining insulin sensitivity, normal adipose tissue homeostasis and systemic metabolism.
Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes
Authors: Polasek-Sedlackova Hana , Miller Thomas C. R. , Krejci Jana , Rask Maj-Britt , Lukas Jiri
Published: October 2022

Genome duplication is safeguarded by constantly adjusting the activity of the replicative CMG (CDC45-MCM2-7-GINS) helicase. However, minichromosome maintenance proteins (MCMs)—the structural core of the CMG helicase—have never been visualized at sites of DNA synthesis inside a cell (the so-called MCM paradox). Here, we solve this conundrum by showing that anti-MCM antibodies primarily detect inactive MCMs. Upon conversion of inactive MCMs to CMGs, factors that are required for replisome activity bind to the MCM scaffold and block MCM antibody binding sites. Tagging of endogenous MCMs by CRISPR-Cas9 bypasses this steric hindrance and enables MCM visualization at active replisomes. Thus, by defining conditions for detecting the structural core of the replicative CMG helicase, our results explain the MCM paradox, provide visual proof that MCMs are an integral part of active replisomes in vivo, and enable the investigation of replication dynamics in living cells exposed to a constantly changing environment.
Concerted expansion and contraction of immune receptor gene repertoires in plant genomes
Authors: Ngou Bruno Pok Man , Heal Robert , Wyler Michele , Schmid Marc W. , Jones Jonathan D. G.
Published: October 2022

Recent reports suggest that cell-surface and intracellular immune receptors function synergistically to activate robust defence against pathogens, but whether they co-evolve is unclear. Here we determined the numbers of cell-surface and intracellular immune receptors in 350 species. Surprisingly, the number of receptor genes that are predicted to encode cell-surface and intracellular immune receptors is strongly correlated. We suggest this is consistent with mutual potentiation of immunity initiated by cell-surface and intracellular receptors being reflected in the concerted co-evolution of the size of their repertoires across plant species.
Amplitude and frequency modulation of subthalamic beta oscillations jointly encode the dopaminergic state in Parkinson’s disease
Authors: Averna Alberto , Marceglia Sara , Priori Alberto , Foffani Guglielmo
Published: October 2022

Brain states in health and disease are classically defined by the power or the spontaneous amplitude modulation (AM) of neuronal oscillations in specific frequency bands. Conversely, the possible role of the spontaneous frequency modulation (FM) in defining pathophysiological brain states remains unclear. As a paradigmatic example of pathophysiological resting states, here we assessed the spontaneous AM and FM dynamics of subthalamic beta oscillations recorded in patients with Parkinson’s disease before and after levodopa administration. Even though AM and FM are mathematically independent, they displayed negatively correlated dynamics. First, AM decreased while FM increased with levodopa. Second, instantaneous amplitude and instantaneous frequency were negatively cross-correlated within dopaminergic states, with FM following AM by approximately one beta cycle. Third, AM and FM changes were also negatively correlated between dopaminergic states. Both the slow component of the FM and the fast component (i.e. the phase slips) increased after levodopa, but they differently contributed to the AM-FM correlations within and between states. Finally, AM and FM provided information about whether the patients were OFF vs. ON levodopa, with partial redundancy and with FM being more informative than AM. AM and FM of spontaneous beta oscillations can thus both separately and jointly encode the dopaminergic state in patients with Parkinson’s disease. These results suggest that resting brain states are defined not only by AM dynamics but also, and possibly more prominently, by FM dynamics of neuronal oscillations.
Giant Berry curvature dipole density in a ferroelectric Weyl semimetal
Authors: Zhang Cheng-Long , Liang Tian , Kaneko Yoshio , Nagaosa Naoto , Tokura Yoshinori
Published: October 2022

The nonlinear Hall effect (NLHE) reflects Berry-curvature-related properties in non-centrosymmetric but time-reversal-symmetric materials. So far, the NLHE of the investigated systems remains a tiny effect due to the lack of Weyl point as magnetic monopoles in 2D systems or to the high carrier concentration in 3D systems. Here, we report large NLHE due to gigantic Berry curvature dipole density as generated by tilted Weyl cones near the Fermi level in a model ferroelectric Weyl semimetal In-doped Pb1−xSnxTe. By systematically lowering the carrier concentration down to ~1016 cm−3, the Berry curvature dipole density reaches values around 10−21 m3, 102–107 times higher than the previously reported ones. Furthermore, NLHE exhibits a power law of carrier concentration and follows the k−2 relation of the Berry curvature expression derived from the monopole. The present study establishes giant NLHE in a ferroelectric Weyl semimetal, promising for future applications such as current rectification.
Fine-scale population spatialization data of China in 2018 based on real location-based big data
Authors: Chen Mingxing , Xian Yue , Huang Yaohuan , Zhang Xiaoping , Hu Maogui , Guo Shasha , Chen Liangkan , Liang Longwu
Published: October 2022

Accurate location-based big data has a high resolution and a direct interaction with human activities, allowing for fine-scale population spatial data to be realized. We take the average of Tencent user location big data as a measure of ambient population. The county-level statistical population data in 2018 was used as the assigned input data. The log linear spatially weighted regression model was used to establish the relationship between location data and statistical data to allocate the latter to a 0.01° grid, and the ambient population data of mainland China was obtained. Extracting street-level (lower than county-level) statistics for accuracy testing, we found that POP2018 has the best fit with the actual permanent population (R2 = 0.91), and the error is the smallest (MSEPOP2018 = 22.48 <MSEWorldPop = 37.24 <MSELandScan = 100.91). This research supplemented in the refined spatial distribution data of people between census years, as well as presenting the application technique of big data in ambient population estimation and zoning mapping.
A novel approach to measure brain-to-brain spatial and temporal alignment during positive empathy
Authors: Toppi J. , Siniatchkin M. , Vogel P. , Freitag C. M. , Astolfi L. , Ciaramidaro A.
Published: October 2022

Empathy is defined as the ability to vicariously experience others’ suffering (vicarious pain) or feeling their joy (vicarious reward). While most neuroimaging studies have focused on vicarious pain and describe similar neural responses during the observed and the personal negative affective involvement, only initial evidence has been reported for the neural responses to others’ rewards and positive empathy. Here, we propose a novel approach, based on the simultaneous recording of multi-subject EEG signals and exploiting the wavelet coherence decomposition to measure the temporal alignment between ERPs in a dyad of interacting subjects. We used the Third-Party Punishment (TPP) paradigm to elicit the personal and vicarious experiences. During a positive experience, we observed the simultaneous presence in both agents of the Late Positive Potential (LPP), an ERP component related to emotion processing, as well as the existence of an inter-subject ERPs synchronization in the related time window. Moreover, the amplitude of the LPP synchronization was modulated by the presence of a human-agent. Finally, the localized brain circuits subtending the ERP-synchronization correspond to key-regions of personal and vicarious reward. Our findings suggest that the temporal and spatial ERPs alignment might be a novel and direct proxy measure of empathy.
A rapid change in magma plumbing taps porphyry copper deposit-forming magmas
Authors: Carter Lawrence C. , Tapster Simon R. , Williamson Ben J. , Buret Yannick , Selby David , Rollinson Gavyn K. , Millar Ian , Parvaz Daniel B.
Published: October 2022

Porphyry-type deposits are a vital source of green technology metals such as copper and molybdenum. They typically form in subduction-related settings from large, long-lived magmatic systems. The most widely accepted model for their formation requires that mantle-derived magmas undergo an increase in volatiles and ore-forming constituents in mid- to lower crustal reservoirs over millions of years, however, this is mostly based on observations from shallow, sporadically exposed parts of porphyry systems. To examine this paradigm, we have evaluated the timeframe and geochemical signatures of magmatism in a ~ 8 km palaeodepth cross-section through plutonic and volcanic rocks of the classic Yerington magmatic system, Nevada. We show that the magmas in the upper parts of the system (< 8 km) underwent a major and rapid change in chemistry over a period of < 200 kyrs that is coincident with the initiation of ore formation. We attribute this change to a shift from extraction of quartz monzodiorite and quartz monzonite magmas evolving in mid-crustal reservoirs, and that had relatively poor ore-forming potential, to extraction of volatile-rich granitic magmas from greater (~ 30 km) depths. As the granites crystallised, late stage melts were intruded through the carapace as aplite dykes which contain traceable expressions of the porphyry deposit-forming fluids. The rapid nature of the shift in ore-forming potential narrows the temporal-geochemical footprint of magmas associated with porphyry mineralisation and provides new constraints for exploration models.
Two-stage variable-fidelity modeling of antennas with domain confinement
Authors: Pietrenko-Dabrowska Anna , Koziel Slawomir , Golunski Lukasz
Published: October 2022

Surrogate modeling has become the method of choice in solving an increasing number of antenna design tasks, especially those involving expensive full-wave electromagnetic (EM) simulations. Notwithstanding, the curse of dimensionality considerably affects conventional metamodeling methods, and their capability to efficiently handle nonlinear antenna characteristics over broad ranges of the system parameters is limited. Performance-driven (or constrained) modeling frameworks may be employed to mitigate these issues by considering a construction of surrogates from the standpoint of the antenna performance figures rather than directly geometry parameters. This permits a significant reduction of the model setup cost without restricting its design utility. This paper proposes a novel modeling framework, which capitalizes on the domain confinement concepts and also incorporates variable-fidelity EM simulations, both at the surrogate domain definition stage, and when rendering the final surrogate. The latter employs co-kriging as a method of blending simulation data of different fidelities. The presented approach has been validated using three microstrip antennas, and demonstrated to yield reliable models at remarkably low CPU costs, as compared to both conventional and performance-driven modeling procedures.
A novel and robust method for counting components within bio-molecular complexes using fluorescence microscopy and statistical modelling
Authors: Mersmann Sophia F. , Johns Emma , Yong Tracer , McEwan Will A. , James Leo C. , Cohen Edward A. K. , Grove Joe
Published: October 2022

Cellular biology occurs through myriad interactions between diverse molecular components, many of which assemble in to specific complexes. Various techniques can provide a qualitative survey of which components are found in a given complex. However, quantitative analysis of the absolute number of molecules within a complex (known as stoichiometry) remains challenging. Here we provide a novel method that combines fluorescence microscopy and statistical modelling to derive accurate molecular counts. We have devised a system in which batches of a given biomolecule are differentially labelled with spectrally distinct fluorescent dyes (label A or B), and mixed such that B-labelled molecules are vastly outnumbered by those with label A. Complexes, containing this component, are then simply scored as either being positive or negative for label B. The frequency of positive complexes is directly related to the stoichiometry of interaction and molecular counts can be inferred by statistical modelling. We demonstrate this method using complexes of Adenovirus particles and monoclonal antibodies, achieving counts that are in excellent agreement with previous estimates. Beyond virology, this approach is readily transferable to other experimental systems and, therefore, provides a powerful tool for quantitative molecular biology.
Investigation of radiomics based intra-patient inter-tumor heterogeneity and the impact of tumor subsampling strategies
Authors: Henry T. , Sun R. , Lerousseau M. , Estienne T. , Robert C. , Besse B. , Robert C. , Paragios N. , Deutsch E.
Published: October 2022

While radiomics analysis has been applied for localized cancer disease, its application to the metastatic setting involves a non-exhaustive lesion subsampling strategy which may sidestep the intrapatient tumoral heterogeneity, hindering the reproducibility and the therapeutic response performance. Our aim was to evaluate if radiomics features can capture intertumoral intrapatient heterogeneity, and the impact of tumor subsampling on the computed heterogeneity. To this end, We delineated and extracted radiomics features of all visible tumors from single acquisition pre-treatment computed tomography of patients with metastatic lung cancer (cohort L) and confirmed our results on a larger cohort of patients with metastatic melanoma (cohort M). To quantify the captured heterogeneity, the absolute coefficient of variation (CV) of each radiomics index was calculated at the patient-level and a sensitivity analysis was performed using only a subset of all extracted features robust to the segmentation step. The extent of information loss by six commonly used tumor sampling strategies was then assessed. A total of 602 lesions were segmented from 43 patients (median age 57, 4.9% female). All robust radiomics indexes exhibited at least 20% of variation with significant heterogeneity both in heavily and oligo metastasized patients, and also at the organ level. None of the segmentation subsampling strategies were able to recover the true tumoral heterogeneity obtained by exhaustive tumor sampling. Image-based inter-tumor intra-patient heterogeneity can be successfully grasped by radiomics analyses. Failing to take into account this kind of heterogeneity will lead to inconsistent predictive algorithms. Guidelines to standardize the tumor sampling step and/or AI-driven tools to alleviate the segmentation effort are required.
Brief overview of dietary intake, some types of gut microbiota, metabolic markers and research opportunities in sample of Egyptian women
Authors: Hassan Nayera E. , El Shebini Salwa M. , El-Masry Sahar A. , Ahmed Nihad H. , Kamal Ayat N. , Ismail Ahmed S. , Alian Khadija M. , Mostafa Mohammed I. , Selim Mohamed , Afify Mahmoud A. S.
Published: October 2022

Metabolic syndrome (MetS) is a phenotype caused by the interaction of host intrinsic factors such as genetics and gut microbiome, and extrinsic factors such as diet and lifestyle. To demonstrate the interplay of intestinal microbiota with obesity, MetS markers, and some dietary ingredients among samples of Egyptian women. This study was a cross-sectional one that included 115 Egyptian women; 82 were obese (59 without MetS and 23 with MetS) and 33 were normal weight. All participants were subjected to anthropometric assessment, 24 h dietary recall, laboratory evaluation of liver enzymes (AST and ALT), leptin, short chain fatty acids (SCFA), C-reactive protein, fasting blood glucose, insulin, and lipid profile, in addition to fecal microbiota analysis for Lactobacillus, Bifidobacteria, Firmicutes, and Bacteroid. Data showed that the obese women with MetS had the highest significant values of the anthropometric and the biochemical parameters. Obese MetS women consumed a diet high in calories, protein, fat, and carbohydrate, and low in fiber and micronutrients. The Bacteroidetes and Firmicutes were the abundant bacteria among the different gut microbiota, with low Firmicutes/Bacteroidetes ratio, and insignificant differences between the obese with and without MetS and normal weight women were reported. Firmicutes/Bacteroidetes ratio significantly correlated positively with total cholesterol and LDL-C and negatively with SCFA among obese women with MetS. Findings of this study revealed that dietary factors, dysbiosis, and the metabolic product short chain fatty acids have been implicated in causing metabolic defects.
KIR-HLA gene diversities and susceptibility to lung cancer
Authors: Hematian Larki Marjan , Ashouri Elham , Barani Shaghik , Ghayumi Seiyed Mohammad Ali , Ghaderi Abbas , Rajalingam Raja
Published: October 2022

Killer-cell immunoglobulin-like receptors (KIR) are essential for acquiring natural killer (NK) cell effector function, which is modulated by a balance between the net input of signals derived from inhibitory and activating receptors through engagement by human leukocyte antigen (HLA) class I ligands. KIR and HLA loci are polygenic and polymorphic and exhibit substantial variation between individuals and populations. We attempted to investigate the contribution ofKIRcomplex andHLA class Iligands to the genetic predisposition to lung cancer in the native population of southern Iran. We genotyped 16KIRgenes for a total of 232 patients with lung cancer and 448 healthy controls (HC), among which 85 patients and 178 HCs were taken into account for evaluating combinedKIR-HLAassociations.KIR2DL2and2DS2were increased significantly in patients than in controls, individually (OR 1.63, and OR 1.42, respectively) and in combination withHLA-C1ligands (OR 1.99, and OR 1.93, respectively).KIR3DS1(OR 0.67) and2DS1(OR 0.69) were more likely presented in controls in the absence of their relative ligands. The incidence of CxTx subset was increased in lung cancer patients (OR 1.83), and disease risk strikingly increased by more than fivefold among genotype ID19 carriers (a CxTx genotype that carries2DL2in the absence of2DS2, OR 5.92). We found that genotypes withiKIRs > aKIRs(OR 1.67) were more frequently presented in lung cancer patients. Additionally, patients with lung cancer were more likely to carry the combination of CxTx/2DS2compared to controls (OR 2.04), andiKIRs > aKIRsgenotypes in the presence of2DL2(OR 2.05) increased the likelihood of lung cancer development. Here we report new susceptibility factors and the contribution ofKIRandHLA-Iencoding genes to lung cancer risk, highlighting an array of genetic effects and disease setting which regulates NK cell responsiveness. Our results suggest that inheritedKIRgenes andHLA-Iligands specifying the educational state of NK cells can modify lung cancer risk.
Methods and reference data for middle ear transfer functions
Authors: Koch M. , Eßinger T. M. , Maier H. , Sim J. H. , Ren L. , Greene N. T. , Zahnert T. , Neudert M. , Bornitz M.
Published: October 2022

Human temporal bone specimens are used in experiments measuring the sound transfer of the middle ear, which is the standard method used in the development of active and passive middle ear implants. Statistical analyses of these experiments usually require that the TB samples are representative of the population of non-pathological middle ears. Specifically, this means that the specimens must be mechanically well-characterized. We present an in-depth statistical analysis of 478 data sets of middle ear transfer functions (METFs) from different laboratories. The data sets are preprocessed and various contributions to the variance of the data are evaluated. We then derive a statistical range as a reference against which individual METF measurements may be validated. The range is calculated as the two-sided 95% tolerance interval at audiological frequencies. In addition, the mean and 95% confidence interval of the mean are given as references for assessing the validity of a sample group. Finally, we provide a suggested procedure for measuring METFs using the methods described herein.
Rapid adsorption of selenium removal using iron manganese-based micro adsorbent
Authors: Qureshi Sundus Saeed , Memon Sheeraz Ahmed , Rafi-ul-Zaman  , Ram Nanik , Saeed Sumbul , Mubarak Nabisab Mujawar , Karri Rama Rao
Published: October 2022

Selenium in wastewater is of particular concern due to its increasing concentration, high mobility in water, and toxicity to organisms; therefore, this study was carried out to determine the removal efficiency of selenium using iron and manganese-based bimetallic micro-composite adsorbents. The bimetallic micro-composite adsorbent was synthesized by using the chemical reduction method. Micro-particles were characterized by using energy-dispersive X-ray spectroscopy for elemental analysis after adsorption, which confirms the adsorption of selenium on the surface of the micro-composite adsorbent, scanning electron microscopy, which shows particles are circular in shape and irregular in size, Brunauer–Emmett–Teller which results from the total surface area of particles were 59.345m2/g, Zeta particle size, which results from average particles size were 39.8 nm. Then it was applied to remove selenium ions in an aqueous system. The data revealed that the optimum conditions for the highest removal (95.6%) of selenium were observed at pH 8.5, adsorbent dosage of 25 mg, and contact time of 60 min, respectively, with the initial concentration of 1 ppm. The Langmuir and Freundlich isotherm models match the experimental data very well. The results proved that bimetallic micro-composite could be used as an effective selenium adsorbent due to the high adsorption capacity and the short adsorption time needed to achieve equilibrium. Regarding the reusability of bimetallic absorbent, the adsorption and desorption percentages decreased from 50 to 45% and from 56 to 53%, respectively, from the 1st to the 3rd cycle.
Diagnostic performance of convolutional neural networks for dental sexual dimorphism
Authors: Franco Ademir , Porto Lucas , Heng Dennis , Murray Jared , Lygate Anna , Franco Raquel , Bueno Juliano , Sobania Marilia , Costa Márcio M. , Paranhos Luiz R. , Manica Scheila , Abade André
Published: October 2022

Convolutional neural networks (CNN) led to important solutions in the field of Computer Vision. More recently, forensic sciences benefited from the resources of artificial intelligence, especially in procedures that normally require operator-dependent steps. Forensic tools for sexual dimorphism based on morphological dental traits are available but have limited performance. This study aimed to test the application of a machine learning setup to distinguish females and males using dentomaxillofacial features from a radiographic dataset. The sample consisted of panoramic radiographs (n = 4003) of individuals in the age interval of 6 and 22.9 years. Image annotation was performed with V7 software (V7labs, London, UK). From Scratch (FS) and Transfer Learning (TL) CNN architectures were compared, and diagnostic accuracy tests were used. TL (82%) performed better than FS (71%). The correct classifications of females and males aged ≥ 15 years were 87% and 84%, respectively. For females and males < 15 years, the correct classifications were 80% and 83%, respectively. The Area Under the Curve (AUC) from Receiver-operating Characteristic (ROC) curves showed high classification accuracy between 0.87 and 0.91. The radio-diagnostic use of CNN for sexual dimorphism showed positive outcomes and promising forensic applications to the field of dental human identification.