bluuebunny/crossref_metadata_2025 huggingface dataset:
Choosing Women in Postwar Elections: Exposure to War Violence, Ideology, and Voters’ Gender Bias
Authors: Glaurdić Josip , Lesschaeve Christophe
Published: February 2023

The level of women’s parliamentary representation often increases after armed conflict, but do voters in postwar societies actually prefer female electoral candidates? We answer this question by analyzing a unique data set containing information on nearly 7,000 candidates running in three elections with preferential voting in postwar Croatia. Our analysis demonstrates that voters’ gender bias is conditional on the local electorate’s ideology and exposure to war violence, with voters of right-wing parties and voters in areas more affected by war violence being more biased against female candidates. These effects of ideology and exposure to war violence also exhibit a strong interactive relationship, suggesting that bias against women is strongest among right-wing voters in areas exposed to war violence and reversed among left-wing voters in areas exposed to war violence. Our findings highlight the need to better understand the relationship between gender, ideology, and violence in postconflict societies.
Land and the Language of Race: State Colonization and the Privatization of Indigenous Lands in Araucanía, Chile (1871–1916)
Authors: Rioja Romina Green
Published: February 2023

This article explores the vision, process, and reaction to the privatization of Mapuche lands in Araucanía, Chile, from 1871 to 1916. It shows how politicians developed a racial vision for Araucanía between 1871 and 1882 during the final battle with independent Mapuche forces. Chilean government officials and elite societies created land policies that targeted the removal of indigenous populations from fertile lands to expand industrial agriculture by favoring large Chilean-owned estates and partitioning small to medium-sized plots to European settler-farmers. From 1883 to 1896, the Chilean government put its vision into practice, investing in the recruitment of European farmers and reconsidering new laws regarding colonization, land rights, and indigenous settlements. However, after the 1891 civil war, the government retreated from expensive state-building projects. From 1896 to 1916, Chilean small farmers intensified land grabs and, in response, indigenous communities formed organizations to defend their lands. At the core of the conflict were the issues of land and racialized policies that defined land access. By examining laws, government reports, missionary chronicles, and indigenous writings, this article demonstrates the progression of a racialized language that excluded indigenous peoples from their lands, founded in the desire to privatize native lands and accelerate the making of a modern Europeanized nation.
Immigrants’ Dual Identity and the Hostile Media Effect in the Context of Sports Broadcasts
Authors: Kim Hyunjung
Published: February 2023

Abstract: We explored how immigrants’ dual (ethno-national) identity affects the hostile media effect in the context of broadcast news of international sporting events. A mixed-methods approach to collecting data was used comprising an online experiment and in-person focus group interviews with Korean Chinese immigrants residing in South Korea. The results demonstrate that hostile media perception in favor of the out-group was greater for out-group broadcast news than for in-group broadcast news. The hostile media perception was linked to support for in-group players only for immigrants with a strong dual identity. The results of the focus group interviews suggest that the dual-identity participants reinforce their national identity and increase their support for the in-group players to deal with the threat to their self-esteem when collective self-esteem connected to their national identity is threatened by what they considered broadcast news biased against Chinese players.
A Large‐Scale Magnetospheric Line Radiation Event in the Upper Ionosphere Recorded by the China‐Seismo‐Electromagnetic Satellite
Authors: Hu Yunpeng , Zhima Zeren , Fu Huishan , Cao Jinbin , Piersanti Mirko , Wang Tieyan , Yang Dehe , Sun Xiaoying , Lv Fangxian , Lu Chao , Wang Qiao , Wang Yalu , Shen Xuhui
Published: February 2023

This paper reports a large‐scale magnetospheric line radiation (MLR) event during a moderate geomagnetic storm on 11 September 2018, which was well recorded by the China‐Seismo‐Electromagnetic Satellite (CSES) in the upper ionosphere. The event shows a symmetrical propagation feature at the conjugated locations between the two hemispheres, exhibiting a large spatial extension roughly from the latitudes 54°N to 53°S. The parallel structures are visible both in the electric and magnetic fields at a frequency band ranging from the local proton cyclotron frequency to ∼1.6 kHz. The wave intensity of parallel spectral lines was primarily enhanced in high latitude regions, gradually weakening at mid‐low latitudes, and then got absorbed in the equatorial region, presenting a distinct V‐shaped structure. The frequency spacings between neighboring spectral lines roughly vary from ∼80 to 110 Hz at the high latitudes and ∼80–130 Hz at the low latitudes, suggesting a slight variation feature with latitude. The parallel spectral structures of MLR drift between ∼0.39 and 0.57 Hz/s at high latitudes and ∼0.18–0.19 Hz/s at low latitudes. The wave vector analysis shows that the MLR waves are right‐hand polarized, obliquely propagating toward the Earth and in the azimuthal direction, where the Poynting flux is primarily oriented perpendicular to the ambient magnetic field. The other large‐scale MLR events all exhibit similar parallel structures and polarization characteristics, suggesting the universality of such a phenomenon. However, the azimuthal angles differ among different events, showing complex features.
The natural history of a delayed detectable PSA after radical prostatectomy
Authors: Szymaniak Julie A. , Washington Samuel L. , Cowan Janet E. , Cooperberg Matthew R. , Lonergan Peter E. , Nguyen Hao G. , Meng Maxwell V. , Carroll Peter R.
Published: February 2023

Introduction

Men with a detectable PSA after radical prostatectomy (RP) are often offered salvage therapy while those with an undetectable PSA are monitored. We aim to better characterize the natural history of men with an initially undetectable PSA who subsequently developed a detectable PSA > 6 months after RP.

Methods

Retrospective analysis of men who underwent RP for clinically localized prostate cancer at the University of California, San Francisco from 2000 to 2022. The primary outcome was biochemical recurrence, defined as 2 consecutive PSA > = 0.03 ng/mL starting 6 months after surgery. Secondary outcomes were salvage treatment, post-salvage treatment, metastasis free survival (MFS), prostate cancer specific mortality (PCSM), and all-cause mortality (ACM). This cohort was compared to a previously described cohort who had an immediately detectable post-operative PSA.

Results

From our cohort of 3348 patients, we identified 2868 men who had an undetectable post-op PSA. Subsequently, 642 men had a delayed detectable PSA at a median of 25 months (IQR 15, 43) with median follow-up of 72 months after RP. PSA at time of failure was <0.10 ng/mL for 65.7% of men. Of those with a delayed detectable PSA, 46% underwent salvage treatment within 10 years after RP at a median PSA of 0.08 ng/mL (IQR 0.05, 0.14). High CAPRA-S score (HR 1.09, CI 1.02–1.17, p = 0.02) and PSA doubling time (PSA-DT) of <6 months (HR 7.58, CI 5.42–10.6, p < 0.01) were associated with receiving salvage treatment. After salvage treatment, 62% of men had recurrent PSA failure within 10 years. Overall, MFS was 92%, PCSM 3%, and ACM 6% at 10 years. For those who received tertiary treatment for recurrent PSA failure, MFS was 54%, PCSM 23% and ACM 23% at 10 years’ time.

Conclusions

Men who develop a detectable PSA > 6 months post-operatively may have excellent long-term outcomes, even in the absence of salvage therapy.
Preclinical models in head and neck squamous cell carcinoma
Authors: Chaves Patricia , Garrido María , Oliver Javier , Pérez-Ruiz Elisabeth , Barragan Isabel , Rueda-Domínguez Antonio
Published: February 2023

Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based on cell lines and murine models. In this review, we will go over the most frequently used preclinical models, from immortalised-cell and primary tumour cultures in monolayer or 3D, to the currently available animal models. We will scrutinise their efficiency in mimicking the molecular and cellular complexity of head and neck squamous cell carcinoma. Finally, the challenges and the opportunities of other envisaged putative approaches, as well as the potential of the preclinical models to further develop personalised therapies will be discussed.
Clinical trials of self-replicating RNA-based cancer vaccines
Authors: Morse Michael A. , Crosby Erika J. , Force Jeremy , Osada Takuya , Hobeika Amy C. , Hartman Zachary C. , Berglund Peter , Smith Jonathan , Lyerly H. Kim
Published: February 2023

Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. To enhance the immunogenicity of mRNA-delivered epitopes, self-replicating RNAs (srRNA) that markedly increase epitope expression have been developed. These vectors are derived from positive-strand RNA viruses in which the structural protein genes have been replaced with heterologous genes of interest, and the structural proteins are provided in trans to create single cycle viral replicon particles (VRPs). Clinical stage srRNA vectors have been derived from alphaviruses, including Venezuelan Equine Encephalitis (VEE), Sindbis, and Semliki Forest virus (SFV) and have encoded the tumor antigens carcinoembryonic antigen (CEA), human epidermal growth factor receptor 2 (HER2), prostate specific membrane antigen (PSMA), and human papilloma virus (HPV) antigens E6 and E7. Adverse events have mainly been grade 1 toxicities and minimal injection site reactions. We review here the clinical experience with these vaccines and our recent safety data from a study combining a VRP encoding HER2 plus an anti-PD1 monoclonal antibody (pembrolizumab). This experience with VRP-based srRNA supports recent development of fully synthetic srRNA technologies, where the viral structural proteins are replaced with protective lipid nanoparticles (LNP), cationic nanoemulsions or polymers.
Regulatory T cells (Tregs) in liver fibrosis
Authors: Wu Ke-jia , Qian Qu-fei , Zhou Jin-ren , Sun Dong-lin , Duan Yun-fei , Zhu Xi , Sartorius Kurt , Lu Yun-jie
Published: February 2023

The ability of the human liver to both synthesize extracellular matrix(ECM), as well as regulate fibrogenesis, are integral functions to maintaining homoeostasis. Chronic liver injury stimulates fibrogenesis in response to the imbalance between ECM accumulation and fibrosis resolution. Liver disease that induces fibrogenesis is associated with multiple risk factors like hepatitis infection, schistosomiasis, alcohol, certain drugs, toxicants and emerging aetiology like diabetes and obesity. The activation of hepatic stellate cells (HSCs), whose function is to generate and accumulate ECM, is a pivotal event in liver fibrosis. Simultaneously, HSCs selectively promote regulatory T-cells (Tregs) in an interleukin-2–dependent pattern that displays a dual relationship. On the one hand, Tregs can protect HSCs from NK cell attack, while on the other hand, they demonstrate an inhibitory effect on HSCs. This paper reviews the dual role of Tregs in liver fibrogenesis which includes its promotion of immunosuppression, as well as its activation of fibrosis. In particular, the balance between Tregs and the Th17 cell population, which produce interleukin (IL)-17 and IL-22, is explored to demonstrate their key role in maintaining homoeostasis and immunoregulation. The contradictory roles of Tregs in liver fibrosis in different immune microenvironments and molecular pathways need to be better understood if they are to be deployed to manage this disease.
Repositioning linifanib as a potent anti-necroptosis agent for sepsis
Authors: Yu Liang , Yang Kai , He Xiaoyan , Li Min , Gao Lin , Zha Yunhong
Published: February 2023

Sepsis is a systemic inflammatory syndrome (SIRS) caused by acute microbial infection, and it has an extremely high mortality rate. Tumor necrosis factor-α (TNF-α)-induced necroptosis contributes to the pathophysiology of sepsis, so inhibiting necroptosis might be expected to improve clinical outcomes in septic patients. Here we predicted candidate drugs for treating sepsis in silico by combining genes differentially expressed in septic patients and controls combined with interrogation of the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 perturbation database. Sixteen candidate drugs were screened out through bioinformatics analysis, and the top candidate linifanib was validated in cellular and mouse models of TNF-α-induced necroptosis. Cell viability was measured using a luminescent ATP assay, while the effects of linifanib on necroptosis were investigated by western blotting, immunoprecipitation, and RIPK1 kinase assays. Linifanib effectively protected cells from necroptosis and rescued SIRS mice from TNF-α-induced shock and death. In vitro, linifanib directly suppressed RIPK1 kinase activity. In vivo, linifanib effectively reduced overexpressed IL-6, a marker of sepsis severity, in the lungs of SIRS mice. Our preclinical evidence using an integrated in silico and experimental drug repositioning approach supports the potential clinical utility of linifanib in septic patients. Further clinical validation is now warranted.
Plasma GFAP in Parkinson’s disease with cognitive impairment and its potential to predict conversion to dementia
Authors: Tang Yilin , Han Linlin , Li Shiyu , Hu Tianyu , Xu Zhiheng , Fan Yun , Liang Xiaoniu , Yu Huan , Wu Jianjun , Wang Jian
Published: February 2023

Glial fibrillary acidic protein (GFAP) has been suggested as a biomarker for reactive astrogliosis. We measured the levels of plasma GFAP by Simoa in 60 patients with PD with normal cognition, 63 with mild cognitive impairment (PD-MCI), 24 with dementia (PDD) and 15 healthy controls. A subgroup of patients with PD-MCI (n = 31) was followed up for 4.1 ± 2.3 years. Compared with healthy controls, plasma GFAP levels were elevated in patients with PDD (adjusted P < 0.001) and PD-MCI (adjusted P = 0.013) and were negatively correlated with the Mini Mental State Examination (MMSE) score in PD participants. Plasma GFAP predicted MCI-to-dementia conversion with an AUC of 0.90, higher than NfL, Tau and pTau181. Our results support that plasma GFAP has potential value for distinguishing patients with PDD, and predicting MCI-to-dementia conversion in PD.
Integrated cardio-behavioral responses to threat define defensive states
Authors: Signoret-Genest Jérémy , Schukraft Nina , L. Reis Sara , Segebarth Dennis , Deisseroth Karl , Tovote Philip
Published: February 2023

Fear and anxiety are brain states that evolved to mediate defensive responses to threats. The defense reaction includes multiple interacting behavioral, autonomic and endocrine adjustments, but their integrative nature is poorly understood. In particular, although threat has been associated with various cardiac changes, there is no clear consensus regarding the relevance of these changes for the integrated defense reaction. Here we identify rapid microstates that are associated with specific behaviors and heart rate dynamics, which are affected by long-lasting macrostates and reflect context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioral responses—freezing as measured by immobility—is part of an integrated cardio-behavioral microstate mediated by Chx10+ neurons in the periaqueductal gray. Our framework for systematic integration of cardiac and behavioral readouts presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.
Open multi-session and multi-task EEG cognitive Dataset for passive brain-computer Interface Applications
Authors: Hinss Marcel F. , Jahanpour Emilie S. , Somon Bertille , Pluchon Lou , Dehais Frédéric , Roy Raphaëlle N.
Published: February 2023

Brain-Computer Interfaces and especially passive Brain-Computer interfaces (pBCI), with their ability to estimate and monitor user mental states, are receiving increasing attention from both the fundamental research and the applied research and development communities. Testing new pipelines and benchmarking classifiers and feature extraction algorithms is central to further research within this domain. Unfortunately, data sharing in pBCI research is still scarce. The COG-BCI database encompasses the recordings of 29 participants over 3 separate sessions with 4 different tasks (MATB, N-Back, PVT, Flanker) designed to elicit different mental states, for a total of over 100 hours of open EEG data. This dataset was validated on a subjective, behavioral and physiological level, to ensure its usefulness to the pBCI community. Furthermore, a proof of concept is given with an example of mental workload estimation pipeline and results, to ensure that the data can be used for the design and evaluation of pBCI pipelines. This body of work presents a large effort to promote the use of pBCIs in an open science framework.
A subnational reproductive, maternal, newborn, child, and adolescent health and development atlas of India
Authors: Pezzulo Carla , Tejedor-Garavito Natalia , Chan Ho Man Theophilus , Dreoni Ilda , Kerr David , Ghosh Samik , Bonnie Amy , Bondarenko Maksym , Salasibew Mihretab , Tatem Andrew J.
Published: February 2023

Understanding the fine scale and subnational spatial distribution of reproductive, maternal, newborn, child, and adolescent health and development indicators is crucial for targeting and increasing the efficiency of resources for public health and development planning. National governments are committed to improve the lives of their people, lift the population out of poverty and to achieve the Sustainable Development Goals. We created an open access collection of high resolution gridded and district level health and development datasets of India using mainly the 2015–16 National Family Health Survey (NFHS-4) data, and provide estimates at higher granularity than what is available in NFHS-4, to support policies with spatially detailed data. Bayesian methods for the construction of 5 km × 5 km high resolution maps were applied for a set of indicators where the data allowed (36 datasets), while for some other indicators, only district level data were produced. All data were summarised using the India district administrative boundaries. In total, 138 high resolution and district level datasets for 28 indicators were produced and made openly available.
Regression analysis on forward modeling of diffuse optical tomography system for carcinoma cell detection
Authors: Maheswari K. Uma , Thilak M. , SenthilKumar N. , Nagaprasad N. , Jule Leta Tesfaye , Seenivasan Venkatesh , Ramaswamy Krishnaraj
Published: February 2023

The forward model design was employed in the Diffuse Optical Tomography (DOT) system to determine the optimal photonic flux in soft tissues like the brain and breast. Absorption coefficient (mua), reduced scattering coefficient (mus), and photonic flux (phi) were the parameters subjected to optimization. The Box–Behnken Design (BBD) method of the Response Surface Methodology (RSM) was applied to enhance the Diffuse Optical Tomography experimental system. The DC modulation voltages applied to different laser diodes of 850 nm and 780 nm wavelengths and spacing between the source and detector are the two factors operating on three optimization parameters that predicted the result through two-dimensional tissue image contours. The analysis of the Variance (ANOVA) model developed was substantial (R2 =  > 0.954). The experimental results indicate that spacing and wavelength were more influential factors for rebuilding image contour. The position of the tumor in soft tissues is inspired by parameters like absorption coefficient and scattering coefficient, which depend on DC voltages applied to the Laser diode. This regression method predicted the values throughout the studied parameter space and was suitable for enhancement learning of diffuse optical tomography systems. The range of residual error percentage evaluated between experimental and predicted values for mua, mus, and phi was 0.301%, 0.287%, and 0.1%, respectively.
Electrically evoked mismatch negativity responses to loudness and pitch cues in cochlear implant users
Authors: Wagner Luise , Ladek Anna S. , Plontke Stefan K. , Rahne Torsten
Published: February 2023

Objective measurements could improve cochlear implant (CI) fitting, especially for CI users who have difficulty assessing their hearing impressions. In this study, we investigated the electrically evoked mismatch negativity (eMMN) brain potential as a mainly preattentive response to pitch and loudness changes. In an electrophysiological exploratory study with 21 CI users, pitch and loudness cues were presented in controlled oddball paradigms that directly electrically stimulated the CI via software. Out of them 17 valid data sets were analyzed. A pitch cue was produced by changing the stimulating CI electrodes (pairs of adjacent electrodes). A loudness cue originated from changing the stimulation amplitude on one CI electrode. MMN responses were measured unsing clinical electroencephalography recording according to a standard recording protocol. At the group level, significant eMMN responses were elicited for loudness cues and for pitch cues at basal electrode pairs but not at apical electrode pairs. The effect of deviance direction was not significant and no stimulus artifacts were observed. Recording an electrically evoked MMN in response to loudness changes in CI users is generally feasible, and is, therefore, promising to support CI fitting procedures in the future. Detection of pitch cues would require a greater electrode distance between selected electrodes for standard and deviant stimuli, especially in apical regions. A routine clinical setup can be used to measure eMMN.
Regulation of pseurotin A biosynthesis by GliZ and zinc in Aspergillus fumigatus
Authors: Seo Hyewon , Kang Suzie , Lee Dongho , Yun Cheol-Won
Published: February 2023

Recently, we reported that zinc regulates gliotoxin biosynthesis via ZafA, which is a zinc-responsive transcriptional activator. From an HPLC analysis of culture media of Aspergillus fumigatus, we found a trend of decreasing gliotoxin production but increasing pseurotin A and fumagillin production in proportion to the zinc concentration. The expression of the genes involved in pseurotin A biosynthesis was upregulated under high zinc concentrations. Furthermore, upregulated expression of pseurotin A biosynthetic genes and higher production of pseurotin A were observed in the zafA deletion strain. Interestingly, the deletion of gliZ, a transcriptional activator of gliotoxin biosynthesis genes, resulted in upregulated expression of pseurotin A biosynthetic genes and increased production of pseurotin A. We detected upregulation of fumR expression in the gliZ and zafA deletion mutants. The overexpression of gliZ observed in the zafA deletion mutant resulted in the failure of the mutant to increase pseurotin A production, which is a phenotype of the zafA deletion mutant. These results suggest that ZafA sequentially regulates pseurotin A biosynthesis through GliZ. Finally, we found through a murine virulence test that the gliZ and fumR double-deletion mutants showed a delayed death rate compared with the single-deletion mutants of either gliZ or fumR. Taken together, these results suggested that the biosynthesis of gliotoxin and pseurotin A are regulated in opposite ways by zinc utilization and that each secondary metabolite is synthesized when the synthesis of another secondary metabolite fails to protect it against the defense system of the host.
Evidence from ClinicalTrials.gov on the growth of Digital Health Technologies in neurology trials
Authors: Masanneck Lars , Gieseler Pauline , Gordon William J. , Meuth Sven G. , Stern Ariel D.
Published: February 2023

Digital Health Technologies (DHTs) such as connected sensors offer particular promise for improving data collection and patient empowerment in neurology research and care. This study analyzed the recent evolution of the use of DHTs in trials registered on ClinicalTrials.gov for four chronic neurological disorders: epilepsy, multiple sclerosis, Alzheimer’s, and Parkinson’s disease. We document growth in the collection of both more established digital measures (e.g., motor function) and more novel digital measures (e.g., speech) over recent years, highlighting contexts of use and key trends.
Oxygen transfer reaction of haloalkyl amides catalyzed by phenylboronic acid
Authors: Sen Abhijit , Muranaka Atsuya , Ohno Aya , Yamada Yoichi M. A.
Published: February 2023

Nitrile derivatives are important building blocks in organic synthesis. Herein, we report the serendipitous discovery of an oxygen transfer reaction that produces hydroxyalkyl nitriles from the sequential dehydration and hydrolysis of haloalkyl amides. Product yields of up to 91% were achieved, and the phenylboronic acid was recovered as triphenylboroxine. The triphenylboroxine was reused as a catalyst without any loss of catalytic activity. A probable catalytic pathway was proposed based on control experiments and DFT calculations.
Multi-responsive chitosan-based hydrogels for controlled release of vincristine
Authors: Farasati Far Bahareh , Omrani Mohsen , Naimi Jamal Mohammad Reza , Javanshir Shahrzad
Published: February 2023

As medical research progresses, the derivation and development of biological materials such as hydrogels have steadily gained more interest. The biocompatibility and non-toxicity of chitosan make chitosan hydrogels potential carriers for drug delivery. This work aims to develop two multi-reactive, safe, and highly swellable bio-hydrogels consisting of chitosan-graft-glycerol (CS-g-gly) and carboxymethyl chitosan-graft-glycerol (CMCS-g-gly), for sustained and controlled drug release, improved bioavailability along with entrapment in nanocarriers, which reduces side effects of vincristine sulphate. CS-g-gly and CMCS-g-gly are successfully prepared and fully characterized using analytical techniques. Under various conditions, the prepared hydrogels exhibit a high swelling ratio. Vincristine-loaded CS-g-gly (VCR/CS-g-gly), and CMCS-g-gly (VCR/CMCS-g-gly) show high encapsulation efficiency between 72.28-89.97%, and 56.97-71.91%, respectively. VCR/CS-g-gly show a sustained release behavior, and the maximum release of VCR from hydrogels reached 82% after 120 h of incubation. MCF-7 (breast cancer cell line) and MCF-10 (normal breast cell line) are evaluated for cell viability and apoptosis induction. The in-vitro anti-tumor efficacy is investigated using flow cytometry. The tetrazolium-based MTT assay of hydrogels shows no evidence of significant cytotoxicity in MCF-7 and MCF-10 cells. According to these findings, these hydrogels can effectively deliver drugs to MCF-7 and other breast cancer cells.
A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAFV600E colorectal tumors
Authors: Ruiz-Saenz Ana , Atreya Chloe E. , Wang Changjun , Pan Bo , Dreyer Courtney A. , Brunen Diede , Prahallad Anirudh , Muñoz Denise P. , Ramms Dana J. , Burghi Valeria , Spassov Danislav S. , Fewings Eleanor , Hwang Yeonjoo C. , Cowdrey Cynthia , Moelders Christina , Schwarzer Cecilia , Wolf Denise M. , Hann Byron , VandenBerg Scott R. , Shokat Kevan , Moasser Mark M. , Bernards René , Gutkind J. Silvio , van ‘t Veer Laura J. , Coppé Jean-Philippe
Published: February 2023

BRAFV600E mutation confers a poor prognosis in metastatic colorectal cancer (CRC) despite combinatorial targeted therapies based on the latest understanding of signaling circuitry. To identify parallel resistance mechanisms induced by BRAF–MEK–EGFR co-targeting, we used a high-throughput kinase activity mapping platform. Here we show that SRC kinases are systematically activated in BRAFV600E CRC following targeted inhibition of BRAF ± EGFR and that coordinated targeting of SRC with BRAF ± EGFR increases treatment efficacy in vitro and in vivo. SRC drives resistance to BRAF ± EGFR targeted therapy independently of ERK signaling by inducing transcriptional reprogramming through β-catenin (CTNNB1). The EGFR-independent compensatory activation of SRC kinases is mediated by an autocrine prostaglandin E2 loop that can be blocked with cyclooxygenase-2 (COX2) inhibitors. Co-targeting of COX2 with BRAF + EGFR promotes durable suppression of tumor growth in patient-derived tumor xenograft models. COX2 inhibition represents a drug-repurposing strategy to overcome therapeutic resistance in BRAFV600E CRC.
Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
Authors: Waziry R. , Ryan C. P. , Corcoran D. L. , Huffman K. M. , Kobor M. S. , Kothari M. , Graf G. H. , Kraus V. B. , Kraus W. E. , Lin D. T. S. , Pieper C. F. , Ramaker M. E. , Bhapkar M. , Das S. K. , Ferrucci L. , Hastings W. J. , Kebbe M. , Parker D. C. , Racette S. B. , Shalev I. , Schilling B. , Belsky D. W.
Published: February 2023

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1–3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5–7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11–13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14–16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18–20.
DNA methylation age acceleration is associated with risk of diabetes complications
Authors: Vetter Valentin Max , Spieker Johanne , Sommerer Yasmine , Buchmann Nikolaus , Kalies Christian Humberto , Regitz-Zagrosek Vera , Bertram Lars , Demuth Ilja
Published: February 2023

Background

Patients with Type 2 diabetes mellitus (T2D) are at risk for micro- and macrovascular complications. Implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The epigenetic clock estimates an individual’s biological age using DNA methylation profiles.

Methods

In this study, we examined older adults of the Berlin Aging Study II that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. DNA methylation age (DNAmA) and its deviation from chronological age DNAmA acceleration (DNAmAA) were calculated with the 7-CpG clock (available at both timepoints,n = 1,071), Horvath’s clock, Hannum’s clock, PhenoAge and GrimAge (available at follow-up only,n = 1,067). T2D associated complications were assessed with the Diabetes Complications Severity Index (DCSI).

Results

We report on a statistically significant association between oral glucose tolerance test results and Hannum and PhenoAge DNAmAA. PhenoAge was also associated with fasting glucose. In contrast, we found no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of T2D. However, longitudinal analyses showed that every additional year of 7-CpG DNAmAA at baseline increased the odds for developing one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with T2D. This association persisted after covariate adjustment (OR = 1.11,p = 0.045,n = 56).

Conclusion

Although our results remain to be independently validated, this study shows promising evidence of utility of the 7-CpG clock in identifying patients with diabetes who are at high risk for developing complications.
Portable detection of multiple mycotoxins based on a sonic toothbrush, microfluidic chip and smartphone
Authors: Zhou Yuan , Ma Longping , Luo Lei , Xiang Dongliu , Wang Qing , Luan Yanan , Huang Jin , Liu Jianbo , Yang Xiaohai , Wang Kemin
Published: February 2023

A portable method for mycotoxin detection was developed based on a sonic toothbrush, microfluidic chip and smartphone, without any sophisticated instruments.
Computational determination of a graphene-like TiB4 monolayer for metal-ion batteries and a nitrogen reduction electrocatalyst
Authors: Li Yameng , Yang Weihua , Yu Fangqi , Huang Rao , Wen Yuhua
Published: February 2023

The electrochemical performances of a graphene-like TiB4 monolayer as a high-efficiency anode material for Li/Na/K-ion batteries and a NRR electrocatalyst were investigated by using first-principles calculations.
Towards higher scientific validity and regulatory acceptance of predictive models for PFAS
Authors: Sosnowska Anita , Bulawska Natalia , Kowalska Dominika , Puzyn Tomasz
Published: February 2023

This study aims at the evaluation of the available QSAR/QSPR models for PFAS and highlights the gaps and defines further challenges related to applying computational methods for predicting the activity and properties of PFAS.
Research advancement in molten salt-mediated thermochemical upcycling of biomass waste
Authors: Shen Yafei , Yuan Xiangzhou
Published: February 2023

This paper discusses the research development and future challenges in molten salt-mediated thermochemical conversion of biomass waste into chemicals, fuels and advanced carbon materials.
The 2D microfluidics cookbook – modeling convection and diffusion in plane flow devices
Authors: Boulais Etienne , Gervais Thomas
Published: February 2023

A step-by-step guide for the design and analysis of 2D microfluidic technologies.
Dimeric polyphenols to pave the way for new antimalarial drugs
Authors: Degotte Gilles , Pendeville Hélène , Di Chio Carla , Ettari Roberta , Pirotte Bernard , Frédérich Michel , Francotte Pierre
Published: February 2023

A polyphenolic scaffold to develop novel orally active antimalarials against resistant Plasmodium falciparum.
Facile synthesis of porous LiMn2O4 nano-cubes for ultra-stable lithium-ion battery cathodes
Authors: Cheng Haiyun , Ma Caiyu , Li Wenyao
Published: February 2023

Spinel LiMn2O4 nano-cubes exhibited excellent electrochemical performance with 90.91% capacity retention after 500 cycles.
A poly-pseudorotaxane constructed by threading pillar[5]arene onto an ion-pair recognition-based calix[4]pyrrole supramolecular polymer
Authors: Bektas Necla , Aydogan Abdullah
Published: February 2023

The ion-pair recognition ability of octamethylcalix[4]pyrrole is used to construct supramolecular multicomponent single and polymeric assemblies that can form pseudorotaxanes with pillar[5]arene.
Regioselective synthesis of enantiopure 1,2- and 1,3-dispirooxindoles along with a DFT study
Authors: Asmari Bardazard Kamal , Shahrestani Naeimeh , Zamani Amirhosein , Eskandari Mehdi , Jadidi Khosrow , Hamzehloueian Mahshid , Notash Behrouz
Published: February 2023

The regio- and diastereoselective synthesis of rigid framework dispirooxindole [indolizidine, pyrrolizidine, and pyrrolidine] derivatives as enantiopure products in 1,2 and 1,3-dispiro regioisomeric forms is reported.
The interplay between chemo-phoretic interactions and crowding in active colloids
Authors: Fadda Federico , Matoz-Fernandez Daniel A. , van Roij René , Jabbari-Farouji Sara
Published: February 2023

Competition between long-range attractive chemophoretic interactions and self-propulsion in active colloids leads to a new kind of phase separation at moderate activities and low densities that we call chemo-motility induced phase separation.
Nanomaterials as multimodal photothermal agents (PTAs) against ‘Superbugs’
Authors: Roy Shubham , Roy Jhilik , Guo Bing
Published: February 2023

This study demonstrates the recent advancements of multimodal photothermal applications in order to ablate superbugs by using functional nanomaterials.
Correction: Controlling CO2 hydrogenation selectivity by Rh-based catalysts with different crystalline phases of TiO2
Authors: Cao Fenghai , Gong Nana , Ma Zixuan , Wang Xiaoxing , Tan Minghui , Wu Yingquan , Tan Yisheng
Published: February 2023

Correction for ‘Controlling CO2 hydrogenation selectivity by Rh-based catalysts with different crystalline phases of TiO2’ by Fenghai Cao et al., Chem. Commun., 2022, 58, 4219–4222, https://doi.org/10.1039/D2CC00472K.
Iridium-catalyzed selective amination of B(4)–H for the synthesis ofo-carborane-fused indolines
Authors: Zhang Cai-Yan , Cao Ke , Liu Dechun , Yang Han-Bo , Teng Chao-Chao , Li Bo , Yang Junxiao
Published: February 2023

An iridium-catalyzed selective amination of B(4)–Hviadehydrogenative cross-coupling of B–H/N–H bonds for the synthesis ofo-carborane-fused indolines has been developed for the first time.
CuCoO2 nanocrystals derived from an isopropanol-modified Cu-BTC using alkaline water oxidation
Authors: Ma Shiyu , Yang Miao , Han Na , Shi Lifen , Wang Liang , Bai Jilin , Xiong Dehua
Published: February 2023

The IPA species can affect the morphology and composition of CCO nanocrystals by tailoring the structure of Cu-BTC precursors, resulting in Cu-BTC-IPA-derived CCO2 catalysts exhibiting better OER performance.
“Breaking bud”: the effect of direct chemical modifications of phytocannabinoids on their bioavailability, physiological effects, and therapeutic potential
Authors: Banerjee Abhinandan , Hayward John J. , Trant John F.
Published: February 2023

The derivatization of THC and CBD for improved bioactivity is reviewed, demonstrating the pharmacophoric versatility, and the limitations of chemical modification, of the cannabinoids. Regulatory and scientific challenges are highlighted.
Efficient thermally activated delayed fluorescence emitters with regioisomeric effects for red/near-infrared organic light-emitting diodes
Authors: Wang Hongbo , Wang Jianghui , Zou Peng , Xu Jingwen , Li Jinshi , Shi Heping , Zhao Zujin , Tang Ben Zhong
Published: February 2023

The regioisomeric effect of cyano substituents on the photoluminescence and electroluminescence properties of thermally activated delayed fluorescence molecules is studied.
Flexible TiN/Ge photodetectors with enhanced responsivity via localized surface plasmon resonance and strain modulation
Authors: Kim You Jin , An Shu , Liao Yikai , Huang Po-Rei , Son Bongkwon , Tan Chuan Seng , Chang Guo-En , Kim Munho
Published: February 2023

Near infrared (NIR) photodetectors (PDs) have attracted great attention for their applications in the field of optical telecommunication.
Targeting NRF2 to promote epithelial repair
Authors: Hiebert Paul , Werner Sabine
Published: February 2023

The transcription factor NRF2 is well known as a master regulator of the cellular stress response. As such, activation of NRF2 has gained widespread attention for its potential to prevent tissue injury, but also as a possible therapeutic approach to promote repair processes. While NRF2 activation affects most or even all cell types, its effect on epithelial cells during repair processes has been particularly well studied. In response to tissue injury, these cells proliferate, migrate and/or spread to effectively repair the damage. In this review, we discuss how NRF2 governs repair of epithelial tissues, and we highlight the increasing number of NRF2 targets with diverse roles in regulating epithelial repair.
Infrared object detection via patch‐tensor model and image denoising based on weighted truncated Schatten‐p norm minimization
Authors: Zhu Yun , Gong Chengjian , Liu Shuwen , Yu Zhiyue , Shao Hanzeng , Yu Gaohang
Published: February 2023

The nuclear norm minimization (NNM) is a special non‐convex rank minimization convex relaxation scheme for image denoising and object detection that requires denoising and background subtraction. Considering excessive shrinkage of rank components and equal treatment of different rank components, NNM is extended to the weighted Schatten‐p norm minimization (WSNM) with weights assigned to different singular values. In this paper, a multi‐channel weighted truncated WSNM model based on the WSNM optimization framework is proposed for RGB colour image denoising. On the basis of different noise intensities and non‐local self‐similar patches of each channel of the colour image itself, the proposed model is improved significantly by the optimization methods of superposition and truncation. Meanwhile, it can be generalized to the tensor space and employed to the infrared imaging target detection based on the spatial‐temporal tensor model for the first time. And the efficient alternating direction multiplier‐based algorithms are developed to solve the proposed model and the accuracy of the algorithm is effectively improved by choosing an adaptive threshold. Extensive experiments on real infrared data verified the proposed method state‐of‐the‐arts and effectiveness.
Interaction of solar jets with filaments: Triggering of large-amplitude filament oscillations
Authors: Joshi Reetika , Luna Manuel , Schmieder Brigitte , Moreno-Insertis Fernando , Chandra Ramesh
Published: February 2023

Context. Large-amplitude oscillations (LAOs) are often detected in filaments. Using multi-wavelength observations, their origin can be traced back to the interaction with eruptions and jets.

Aims. We present two different case studies as observational evidence in support of 2.5D numerical magnetohydrodynamics (MHD) experiments that show that the LAOs in the filament channels can be initiated by solar jets.

Methods. We use longitudinal magnetic field observations using the Helioseismic Magnetic Imager to study the evolution of the filament channels. The LAOs in the filaments are analysed using two techniques. The first is time-distance diagnostics with extreme-ultraviolet (EUV) and Hα datasets. In the second method, the oscillations in different parts of the filaments are examined using Fourier analysis of the brightness variations of all pixels in Hα observations.

Results. In the two studied events, we can identify a quadrupolar configuration with an X-point at the top of the parasitic region suggestive of a classical null-point. The X-point evolves into a flat structure suggestive of a breakout current sheet. A reconnection flow emanates from this structure, leading to a jet that propagates along the filament channel. In both cases, we can identify the quiescent and eruptive phases of the jet. The triggered LAOs have periods of around 70–80 min and are damped after a few oscillations. The minimum magnetic field intensity inferred with seismology for the filament turns out to be around 30 Gauss.

Conclusions. We conclude that the two case studies are consistent with a recently published numerical model in which the LAOs are initiated by jets. The relationship between the onset of the jet and filament oscillations is straightforward for the first case but is less clear for the second case. In the second event, although there is some evidence for a relationship, we cannot rule out other possibilities such as activity unrelated to the null-point or changes in the magnetic structure of the filament. Both jets are associated with very weak flares that did not launch any EUV waves. Therefore, a role of EUV waves in triggering the filament oscillations can be eliminated for these two cases.
A review on Quantum Dots (QDs) and their biomedical applications
Authors: Panja Avirup , Patra Prasun
Published: February 2023

Quantum dots (QDs) are nanoscale semiconductor crystals that possess special characteristics, and they are used in various fields. The crystals are composed of elements that usually lie within the groups II-VI or III–V respectively. The diameter of these crystals is usually smaller than the Bohr excitation radius. These crystals have unique photochemical and photo-physical properties. There are several methods for synthesizing QDs, in which the high temperature co-ordinated solvents-based synthesis is one of the most important. The various synthesis procedures affect the size of these QDs, which determine their characteristics and consequently their applications. QDs are widely used in the fields of bio-imaging, photovoltaic, catalysis, light-emitting diodes, photoconductors, and photodetectors, respectively. The major factors which influence the use of QDs in the field of bio-imaging are their high luminescence, and narrow emission properties. In this review, we discuss various methods of QDs synthesis and their applications in different fields, specifically in today’s world of modern biology.