bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the relationship between perceived worry and self-efficacy in NSW department of education school counsellors
Authors: Donald Sara L. , Walter Emma E.
Published: November 2022

This study investigated the relationship between perceived worry and self-efficacy, with particular attention to job role in Australian school counsellors working in the New South Wales (NSW) Department of Education. Ninety-eight school counsellors ( N = 98, M age = 44.97, SD age = 10.89; 92% female) comprised the sample group, stratified across three job roles: Senior Psychologist Education, School Counsellor, and School Counselling in Training. Data collection tools were the Penn State Worry Questionnaire and the Psychologist and Counsellor Self-Efficacy Scale. Data were analysed using the Pearson product-moment correlation and a multivariate analysis of variance (MANOVA). We found a weak negative association between perceived worry and self-efficacy of significance ( p = .018). Findings demonstrated a significant effect ( p < .001) of job role on the combined dependent variables although the effect was small. Examination of the between-subjects effects demonstrated that role had a significant effect for self-efficacy, but not for worry. Post-hoc analyses showed that individuals in roles of seniority reported higher self-efficacy and lower perceived worry when compared with counsellors in training. Future studies would likely benefit from a more comprehensive consideration of demographic data to ascertain other variables that may be contributing to levels of worry and self-efficacy.
The Death Penalty in Black and White: Execution Coverage in Two Southern Newspapers, 1877–1936
Authors: LaChance Daniel
Published: November 2022

In the immediate aftermath of Reconstruction, coverage of executions in the Atlanta Constitution and the New Orleans (Times-)Picayune occasionally portrayed African Americans executed by the state as legally, politically, and spiritually similar to their white counterparts. But as radical white supremacy took hold across the South, the coverage changed. Through an analysis of 667 newspaper articles covering the executions of Black and white men in Georgia and Louisiana from 1877 to 1936, I found that as lynching became the principal form of lethal punishment in the South, accounts of Black men’s legal executions shrank in length and journalists increasingly portrayed them as ciphers, nonentities that the state was dispatching with little fanfare. In contrast, accounts of white men’s executions continued to showcase their individuality and their membership in social, political, and religious communities. A significant gap between the material reality and the cultural representation of capital punishment emerged. Legal executions in Georgia and Louisiana overwhelmingly targeted Black men. But on the pages of each state’s most prominent newspaper, the executions of white men received the most attention. As a result, capital punishment was increasingly represented as a high-status punishment that respected the “whiteness” of those who suffered it.
Who Dislikes Whom? Affective Polarization between Pairs of Parties in Western Democracies
Authors: Gidron Noam , Adams James , Horne Will
Published: November 2022

While dislike of opposing parties, that is, affective polarization, is a defining feature of contemporary politics, research on this topic largely centers on the United States. We introduce an approach that analyzes affective polarization between pairs of parties, bridging the US two-party system and multiparty systems in other democracies. Analyzing survey data from twenty Western democracies since the mid-1990s, first, we show that partisans' dislike of out-parties is linked to elite policy disagreements on economic issues and, increasingly over time, also to cultural issues. Secondly, we argue and empirically demonstrate that governing coalition partners in parliamentary democracies display much warmer feelings toward each other than we would expect based on elite policy (dis)agreements. Third, we show that radical right parties are disliked much more intensely than we would expect based on policy disputes and coalition arrangements. These findings highlight the policy-based and institutional underpinnings of affective polarization.
Interfaith Dialogue and Mystical Consciousness
Authors: Portilla Isaac
Published: November 2022

This article focuses on the meeting of faith traditions—interfaith dialogue—from the perspective of mystical consciousness. In doing so, it aims to understand the dynamics and potentialities of interfaith mysticism. The contribution of this article to religious studies, in combination with theological inquiry, is threefold: first, it illuminates how the Trinity is directly experienced in interfaith contexts; second, it provides an interfaith framework that accounts for the possibilities, complexity, and challenges of interfaith encounters; third, it shows how Gavin Flood’s three orders of discourse—traditions’ experience and texts, interpretation within traditions, and academic inquiry—can be applied to the study of interfaith mysticism, employing a phenomenological emphasis on hermeneutics. The inquiry is located within the context of representatives of Hindu mystical consciousness (Sri Ramana Maharshi, Sri Aurobindo) and the Christian interfaith tradition (Henri Le Saux, Bede Griffiths, David Steindl-Rast), in conversation with Raimon Panikkar’s and Francis X. Clooney’s approaches to interreligious studies.
The Difficult Airway Redefined
Authors: Burgess Matthew B. , Schauer Steven G. , Hood R. Lyle , De Lorenzo Robert A.
Published: November 2022

There is no all-encompassing or universally accepted definition of the difficult airway, and it has traditionally been approached as a problem chiefly rooted in anesthesiology. However, with airway obstruction reported as the second leading cause of mortality on the battlefield and first-pass success (FPS) rates for out-of-hospital endotracheal intubation (ETI) as low as 46.4%, the need to better understand the difficult airway in the context of the prehospital setting is clear. In this review, we seek to redefine the concept of the “difficult airway” so that future research can target solutions better tailored for prehospital, and more specifically, combat casualty care. Contrasting the most common definitions, which narrow the scope of practice to physicians and a handful of interventions, we propose that the difficult airway is simply one that cannot be quickly obtained. This implies that it is a situation arrived at through a multitude of factors, namely the Patient, Operator, Setting, and Technology (POST), but also more importantly, the interplay between these elements. Using this amended definition and approach to the difficult to manage airway, we outline a target-specific approach to new research questions rooted in this system-based approach to better address the difficult airway in the prehospital and combat casualty care settings.
Stunde Null: Naming and Re-naming
Authors: Erik Larsen Svend
Published: November 2022

Stunde Null – this expression is used to indicate the end of the German Nazi regime in 1945 and the beginning of a new Germany. This historical turning point was marked by the re-naming of the former Germany in both East and West, and Nazi symbols, institutions, values and paraphernalia were taken to the tip. Naming and re-naming were part of this iconoclastic attempt to undo a recent past by turning the memory of it into a negative memory soon to disappear out of sight. However, Vergangenheitsbewältigung is a cumbersome process in which iconoclasm acts both as a singular event and as a moment in an ongoing historical process. The iconoclastic destruction in 1562 of the cathedral in Lyon opens a discussion of the interdependence of event and process in iconoclasm as an intervention in collective memory. Using re-naming to exemplify this cultural dynamic, the motto of the French Revolution, Liberté, Égalité, Fraternité, serves as a brief illustration of how revolutionary iconoclasms were exploited later to redesign French history. To finish, post-colonial India sets the scene for a demonstration of the ambiguities embedded in iconoclastic processes in the short story ‘Lawley Road’ (1956) by R.K. Narayan, an ironic account of a back-and-forth process of re-naming of streets and places in the aftermath of Indian independence.
‘For You Will (Still) Be Here Tomorrow’: The Many Lives of Intergenerational Equity
Authors: Bertram Daniel
Published: November 2022

This article traces the various legal incarnations of the intergenerational equity principle. Despite its silent proliferation in international and constitutional laws over the past five decades, the principle dwelled mostly at the margins of inquiry and practice. Recent efforts to counteract global warming have allowed intergenerational claims to gain new traction. Building on a comparison of ten climate-related lawsuits, I analyze the latest advances in the representation, conceptualization, and remediation of future generations’ interests. Against the backdrop of growing willingness to engage with intergenerational disputes, legal decision makers will need to confront two thorny challenges going forward. Firstly, evolving doctrines of extraterritoriality and legal subjecthood increasingly require the protective scope of the principle to extend to foreign citizens and non-human persons. Secondly, awareness of dispersed and interlocked long-term risks may trigger the application of intergenerational doctrines beyond a narrow environmental frame. Grappling with these challenges implicates larger reflections about the role of law in contriving our collective future.
Development and Validation of a German Interpersonal Sensitivities	Circumplex (ISC-G)
Authors: Müller Sascha , Wendt Leon P. , Schicktanz Paula , Hopwood Christopher J. , Zimmermann Johannes
Published: November 2022

Abstract: The Interpersonal Sensitivities Circumplex (ISC) assesses individual differences in sensitivities to aversive interpersonal behaviors. In this research (total N = 1,519), we developed and validated a German adaptation of the ISC (ISC-G) and extended the nomological net of interpersonal sensitivity as a construct. Using the structural summary method, we investigated associations with self- and informant reports of adaptive (interpersonal) personality traits as well as self-reported personality functioning, maladaptive personality traits, childhood trauma, and hypersensitivity. Replicating and extending previous findings with the ISC, the present research sheds light on the interplay between different personality traits and the perception of others’ interpersonal behavior. Results suggested that individuals report experiencing interpersonal behavior opposite to their own self-description in terms of agency and communion as aversive. This oppositional pattern was most pronounced for antagonistic vs. agreeable traits/behaviors. We discuss these results in the context of research on personality pathology.
Hough Mode Extensions (HMEs) and Solar Tide Behavior in the Dissipative Thermosphere
Authors: Forbes Jeffrey M. , Zhang Xiaoli
Published: November 2022

This paper quantifies and interprets how thermosphere dissipation in the form of molecular viscosity, molecular thermal conductivity and collisions with ions (“ion drag”) determines the height versus latitude structures of a variety of migrating and non‐migrating solar thermal tides, pole‐to‐pole up to 400 km altitude. This is done through computation of thermosphere Hough Mode Extensions (HMEs); that is, solutions to the linearized momentum, thermal energy, continuity, state and hydrostatic balance equations wherein the horizontal structure of troposphere forcing for each HME corresponds to the eigenfunction (Hough function) of Laplace's tidal equation for a particular tidal mode, and the background state and thermosphere dissipation are specified for nominal solar minimum, average and maximum activity conditions. The broad features revealed, different for each HME, include changes in vertical(horizontal) structure with latitude(height), degree of vertical penetration to the middle and upper thermosphere, changes in vertical wavelength (λz) with height due to the transition in background thermal gradient around the mesopause, and insights into role of ion drag in determining tidal amplitudes and their solar cycle variability. The HMEs are particularly useful for fitting measurements of tides, and for estimating tidal fields beyond those dependent variables actually fit and including those outside the fitting domain. The HMEs reported here were created as part of the Ionospheric CONnection (ICON) mission to serve as observation‐based lower boundary conditions for Thermosphere Ionosphere Mesosphere General Circulation Model‐ICON. Access to the full set of HMEs in tabular and graphical form is provided.
Patterns and Drivers of Dissolved Gas Concentrations and Fluxes Along a Low Gradient Stream
Authors: Carter Alice M. , DelVecchia Amanda G. , Bernhardt Emily S.
Published: November 2022

Freshwater ecosystems are globally significant sources of greenhouse gases (GHGs) to the atmosphere. Previous work has indicated that GHG flux in headwater streams is dominated by terrestrially derived gases, with in situ production limited by short organic matter residence times and high dissolved oxygen concentrations due to turbulent reaeration. However, low‐gradient headwater streams that contain pool structures with longer residence times may be conducive to the in situ production of GHG. These streams, and the longitudinal heterogeneity therein, are seldom studied. We measured continuous ecosystem metabolism alongside concentrations and fluxes of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in a low‐gradient third order stream in the North Carolina Piedmont. From autumn to the following spring, we characterized spatial and temporal patterns of GHG along an 8 km segment in the context of channel geomorphology, hydrology, and ecosystem metabolic rates using linear mixed effects models. We found that stream metabolism was responsible for most of the CO2 flux over this period, and that in‐channel aerobic metabolism was a primary predictor of both CH4 and N2O fluxes as well. Long water residence times, limited reaeration, and substantial organic matter from terrestrial inputs foster conditions conducive to the in‐stream accumulation of CO2 and CH4 from microbial respiration. Streams like this one are common in landscapes with low topographic relief, making it likely that the high contribution of instream metabolism to GHG fluxes that we observed is a widespread yet understudied behavior of many small streams.
Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma
Authors: Li Xi-Ya , Wu Ji-Chuan , Liu Ping , Li Zi-Juan , Wang Yong , Chen Bing-Yi , Hu Cheng-Long , Fei Ming-Yue , Yu Peng-Cheng , Jiang Yi-Lun , Xu Chun-Hui , Chang Bin-He , Chen Xin-Chi , Zong Li-Juan , Zhang Jia-Ying , Fang Ying , Sun Xiao-Jian , Xue Kai , Wang Li , Chen Shu-Bei , Jiang Shi-Yu , Gui Ai-ling , Yang Ling , Gu Juan J. , Yu Bao-Hua , Zhang Qun-ling , Wang Lan
Published: November 2022

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.
Beyond fundamental resonance mode: high-order multi-band ALN PMUT for in vivo photoacoustic imaging
Authors: Cai Junxiang , Wang Yiyun , Jiang Daohuai , Zhang Songsong , Gu Yuandong Alex , Lou Liang , Gao Fei , Wu Tao
Published: November 2022

This paper reports on an aluminum nitride (AlN) piezoelectric micromachined ultrasound transducer (PMUT) array for photoacoustic (PA) imaging, where the high-order resonance modes of the PMUT are utilized to improve imaging resolution. A flexural vibration mode (FVM) PMUT is fabricated and applied in a photoacoustic imaging (PAI) system. Specifically, the microelectromechanical system (MEMS)-based PMUT is suitable for PA endoscopic imaging of blood vessels and bronchi due to its miniature size and high sensitivity. More importantly, AlN is a nontoxic material, which makes it harmless for biomedical applications. In the PAI system, the AlN PMUT array is used to detect PA signals, and the acousto–mechanical response is designed and optimized at the PMUT’s fundamental resonance. In this work, we focus on the high-order resonance performance of the PMUT PAI beyond the fundamental resonance. The acoustic and electrical responses of the PMUT’s high-order resonance modes are characterized and analyzed. The fundamental and three high-order resonance bandwidths are 2.2, 8.8, 18.5, and 48.2 kHz. Compared with the resolution at the fundamental resonance mode, the resolutions at third- and fourth-order resonance modes increase by 38.7% and 76.9% in a phantom experiment. The high-order resonance modes of the AlN PMUT sensor array provide higher central frequency and wider bandwidth for PA signal detection, which increase the resolution of PAI compared to the PMUT working at the fundamental resonance mode.
The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy
Authors: Lima Keli , Pereira-Martins Diego Antonio , de Miranda Lívia Bassani Lins , Coelho-Silva Juan Luiz , Leandro Giovana da Silva , Weinhäuser Isabel , Cavaglieri Rita de Cássia , Leal Aline de Medeiros , da Silva Wellington Fernandes , Lange Ana Paula Alencar de Lima , Velloso Elvira Deolinda Rodrigues Pereira , Griessinger Emmanuel , Hilberink Jacobien R. , Ammatuna Emanuele , Huls Gerwin , Schuringa Jan Jacob , Rego Eduardo Magalhães , Machado-Neto João Agostinho
Published: November 2022

The treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates treatment. Genetic models of phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated the relevance of these enzymes in mitochondrial homeostasis and autophagic flux. Here, we uncovered the cellular and molecular effects of THZ-P1-2, a pan-inhibitor of PIP4K2s, in acute leukemia cells. THZ-P1-2 reduced cell viability and induced DNA damage, apoptosis, loss of mitochondrial membrane potential, and the accumulation of acidic vesicular organelles. Protein expression analysis revealed that THZ-P1-2 impaired autophagic flux. In addition, THZ-P1-2 induced cell differentiation and showed synergistic effects with venetoclax. In primary leukemia cells, LC-MS/MS-based proteome analysis revealed that sensitivity to THZ-P1-2 is associated with mitochondrial metabolism, cell cycle, cell-of-origin (hematopoietic stem cell and myeloid progenitor), and the TP53 pathway. The minimal effects of THZ-P1-2 observed in healthy CD34+cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia.
Immune-mediated competition benefits protective microbes over pathogens in a novel host species
Authors: Ford Suzanne A. , Drew Georgia C. , King Kayla C.
Published: November 2022

Microbes that protect against infection inhabit hosts across the tree of life. It is unclear whether and how the host immune system may affect the formation of new protective symbioses. We investigated the transcriptomic response ofCaenorhabditis elegansfollowing novel interactions with a protective microbe (Enterococcus faecalis) able to defend against infection by pathogenicStaphylococcus aureus. We have previously shown thatE. faecaliscan directly limit pathogen growth within hosts. In this study, we show that colonisation by protectiveE. faecaliscaused the differential expression of 1,557 genes in pathogen infected hosts, including the upregulation of immune genes such as lysozymes and C-type lectins. The most significantly upregulated host lysozyme gene,lys-7,impacted the competitive abilities ofE. faecalisandS. aureuswhen knocked out.E. faecalishas an increased ability to resist lysozyme activity compared toS. aureus, suggesting that the protective microbe could gain a competitive advantage from this host response. Our finding that protective microbes can benefit from immune-mediated competition after introduction opens up new possibilities for biocontrol design and our understanding of symbiosis evolution. Crosstalk between the host immune response and microbe-mediated protection should favour the continued investment in host immunity and avoid the potentially risky evolution of host dependence.
Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study
Authors: Etter Manina M. , Martins Tomás A. , Kulsvehagen Laila , Pössnecker Elisabeth , Duchemin Wandrille , Hogan Sabrina , Sanabria-Diaz Gretel , Müller Jannis , Chiappini Alessio , Rychen Jonathan , Eberhard Noëmi , Guzman Raphael , Mariani Luigi , Melie-Garcia Lester , Keller Emanuela , Jelcic Ilijas , Pargger Hans , Siegemund Martin , Kuhle Jens , Oechtering Johanna , Eich Caroline , Tzankov Alexandar , Matter Matthias S. , Uzun Sarp , Yaldizli Özgür , Lieb Johanna M. , Psychogios Marios-Nikos , Leuzinger Karoline , Hirsch Hans H. , Granziera Cristina , Pröbstel Anne-Katrin , Hutter Gregor
Published: November 2022

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.
Photothermal modulated dielectric elastomer actuator for resilient soft robots
Authors: Tan Matthew Wei Ming , Bark Hyunwoo , Thangavel Gurunathan , Gong Xuefei , Lee Pooi See
Published: November 2022

Soft robots need to be resilient to extend their operation under unpredictable environments. While utilizing elastomers that are tough and healable is promising to achieve this, mechanical enhancements often lead to higher stiffness that deteriorates actuation strains. This work introduces liquid metal nanoparticles into carboxyl polyurethane elastomer to sensitize a dielectric elastomer actuator (DEA) with responsiveness to electric fields and NIR light. The nanocomposite can be healed under NIR illumination to retain high toughness (55 MJ m−3) and can be recycled at lower temperatures and shorter durations due to nanoparticle-elastomer interactions that minimize energy barriers. During co-stimulation, photothermal effects modulate the elastomer moduli to lower driving electric fields of DEAs. Bilayer configurations display synergistic actuation under co-stimulation to improve energy densities, and enable a DEA crawler to achieve longer strides. This work paves the way for a generation of soft robots that achieves both resilience and high actuation performance.
Neighborhood Emission Mapping Operation (NEMO): A 1-km anthropogenic emission dataset in the United States
Authors: Ma Siqi , Tong Daniel Q.
Published: November 2022

We present an unprecedented effort to map anthropogenic emissions of air pollutants at 1 km spatial resolution in the contiguous United States (CONUS). This new dataset, Neighborhood Emission Mapping Operation (NEMO), is produced at hourly intervals based on the United States Environmental Protection Agency (US EPA) National Emission Inventories 2017. Fine-scale spatial allocation was achieved through distributing the emission sources using 108 spatial surrogates, factors representing the portion of a source in each 1 km grid. Gaseous and particulate pollutants are speciated into model species for the Carbon Bond 6 chemical mechanism. All sources are grouped in 9 sectors and stored in NetCDF format for air quality models, and in shapefile format for GIS users and air quality managers. This dataset shows good consistency with the USEPA benchmark dataset, with a monthly difference in emissions less than 0.03% for any sector. NEMO provides the first 1 km mapping of air pollution over the CONUS, enabling new applications such as fine-scale air quality modeling, air pollution exposure assessment, and environmental justice studies.
Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia
Authors: Chen Hao , Aneman Ingrid , Nikolic Valentina , Karadzov Orlic Natasa , Mikovic Zeljko , Stefanovic Milan , Cakic Zoran , Jovanovic Hristina , Town Stephanie E. L. , Padula Matthew P. , McClements Lana
Published: November 2022

Preeclampsia is still the leading cause of morbidity and mortality in pregnancy without a cure. There are two phenotypes of preeclampsia, early-onset (EOPE) and late-onset (LOPE) with poorly defined pathogenic differences. This study aimed to facilitate better understanding of the mechanisms of pathophysiology of EOPE and LOPE, and identify specific biomarkers or therapeutic targets. In this study, we conducted an untargeted, label-free quantitative proteomic analyses of plasma samples from pregnant women with EOPE (n = 17) and LOPE (n = 11), and age, BMI-matched normotensive controls (n = 18). Targeted proteomics approach was also employed to validate a subset of proteins (n = 17). In total, there were 26 and 20 differentially abundant proteins between EOPE or LOPE, and normotensive controls, respectively. A series of angiogenic and inflammatory proteins, including insulin-like growth factor-binding protein 4 (IGFBP4; EOPE: FDR = 0.0030 and LOPE: FDR = 0.00396) and inter-alpha-trypsin inhibitor heavy chain H2-4 (ITIH2-4), were significantly altered in abundance in both phenotypes. Through validation we confirmed that ITIH2 was perturbed only in LOPE (p = 0.005) whereas ITIH3 and ITIH4 were perturbed in both phenotypes (p < 0.05). Overall, lipid metabolism/transport proteins associated with atherosclerosis were highly abundant in LOPE, however, ECM proteins had a more pronounced role in EOPE. The complement cascade and binding and uptake of ligands by scavenger receptors, pathways, were associated with both EOPE and LOPE.
Pilot study in human healthy volunteers on the use of magnetohydrodynamics in needle-free continuous glucose monitoring
Authors: Hakala Tuuli A. , Zschaechner Laura K. , Vänskä Risto T. , Nurminen Teemu A. , Wardale Melissa , Morina Jonathan , Boeva Zhanna A. , Saukkonen Reeta , Alakoskela Juha-Matti , Pettersson-Fernholm Kim , Hæggström Edward , Bobacka Johan , García Pérez Alejandro
Published: November 2022

The benefits of continuous glucose monitoring (CGM) in diabetes management are extensively documented. Yet, the broader adoption of CGM systems is limited by their cost and invasiveness. Current CGM devices, requiring implantation or the use of hypodermic needles, fail to offer a convenient solution. We have demonstrated that magnetohydrodynamics (MHD) is effective at extracting dermal interstitial fluid (ISF) containing glucose, without the use of needles. Here we present the first study of ISF sampling with MHD for glucose monitoring in humans. We conducted 10 glucose tolerance tests on 5 healthy volunteers and obtained a significant correlation between the concentration of glucose in ISF samples extracted with MHD and capillary blood glucose samples. Upon calibration and time lag removal, the data indicate a Mean Absolute Relative Difference (MARD) of 12.9% and Precision Absolute Relative Difference of 13.1%. In view of these results, we discuss the potential value and limitations of MHD in needle-free glucose monitoring.
A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination
Authors: Suryadevara Naveenchandra , Kumar Amrendra , Ye Xiang , Rogers Meredith , Williams John V. , Wilson John T. , Karijolich John , Joyce Sebastian
Published: November 2022

Natural infection as well as vaccination with live or attenuated viruses elicit tissue resident, CD8+ memory T cell (Trm) response. Trm cells so elicited act quickly upon reencounter with the priming agent to protect the host. These Trm cells express a unique molecular signature driven by the master regulators—Runx3 and Hobit. We previously reported that intranasal instillation of a subunit vaccine in a prime boost vaccination regimen installed quick-acting, CD8+ Trm cells in the lungs that protected against lethal vaccinia virus challenge. It remains unexplored whether CD8+ Trm responses so elicited are driven by a similar molecular signature as those elicited by microbes in a real infection or by live, attenuated pathogens in conventional vaccination. We found that distinct molecular signatures distinguished subunit vaccine-elicited lung interstitial CD8+ Trm cells from subunit vaccine-elicited CD8+ effector memory and splenic memory T cells. Nonetheless, the transcriptome signature of subunit vaccine elicited CD8+ Trm resembled those elicited by virus infection or vaccination. Clues to the basis of tissue residence and function of vaccine specific CD8+ Trm cells were found in transcripts that code for chemokines and chemokine receptors, purinergic receptors, and adhesins when compared to CD8+ effector and splenic memory T cells. Our findings inform the utility of protein-based subunit vaccination for installing CD8+ Trm cells in the lungs to protect against respiratory infectious diseases that plague humankind.
Machine learning-based detection of label-free cancer stem-like cell fate
Authors: Chambost Alexis J. , Berabez Nabila , Cochet-Escartin Olivier , Ducray François , Gabut Mathieu , Isaac Caroline , Martel Sylvie , Idbaih Ahmed , Rousseau David , Meyronet David , Monnier Sylvain
Published: November 2022

The detection of cancer stem-like cells (CSCs) is mainly based on molecular markers or functional tests giving a posteriori results. Therefore label-free and real-time detection of single CSCs remains a difficult challenge. The recent development of microfluidics has made it possible to perform high-throughput single cell imaging under controlled conditions and geometries. Such a throughput requires adapted image analysis pipelines while providing the necessary amount of data for the development of machine-learning algorithms. In this paper, we provide a data-driven study to assess the complexity of brightfield time-lapses to monitor the fate of isolated cancer stem-like cells in non-adherent conditions. We combined for the first time individual cell fate and cell state temporality analysis in a unique algorithm. We show that with our experimental system and on two different primary cell lines our optimized deep learning based algorithm outperforms classical computer vision and shallow learning-based algorithms in terms of accuracy while being faster than cutting-edge convolutional neural network (CNNs). With this study, we show that tailoring our deep learning-based algorithm to the image analysis problem yields better results than pre-trained models. As a result, such a rapid and accurate CNN is compatible with the rise of high-throughput data generation and opens the door to on-the-fly CSC fate analysis.
Coupled mechanical creep and bio-compression and residual settlement in a multi-stage municipal solid waste landfill, Korea
Authors: Young-Seok Jo , Wan-Kyu Yoo , Sung-Phil Hwang , Chang-Yong Kim
Published: November 2022

Based on a field monitored dataset measured at landfill #1 over 21 years, the characteristics of settlement coupling mechanical creep and biodegradation and the residual settlement were analyzed. Since landfill #1 is a multi-stage municipal solid waste (MSW) landfill where dykes are constructed after landfilling for subsequent waste fills, the waste decomposition between the lower and upper lifts was quite different and it is difficult to discern between the mechanical creep and bio-compression on the settlement curves. The compression ratio coupled with mechanical creep and bio-compression and the residual compression ratio were determined as 0.233 and 0.068, respectively. This implies that biodegradation was gradually and significantly reduced in the MSW settlement behavior after the residual settlement began. The starting date of residual settlement was distributed between 3821 and 5402 days from the initial date of landfilling. The settlement coupling mechanical creep and biodegradation (SMB) was 2.9 times larger than the residual settlement (SRS), and the duration of SMB is determined to be 0.3 times that of SRS. In addition, the remnant methane gas content existed in the landfill gas, and low-level biodegradation was still generated in the waste buried for more than 10 years after the residual settlement began.
Parametric analysis of an efficient boundary condition to control outlet flow rates in large arterial networks
Authors: Lo Sharp C. Y. , McCullough Jon W. S. , Coveney Peter V.
Published: November 2022

Substantial effort is being invested in the creation of a virtual human—a model which will improve our understanding of human physiology and diseases and assist clinicians in the design of personalised medical treatments. A central challenge of achieving blood flow simulations at full-human scale is the development of an efficient and accurate approach to imposing boundary conditions on many outlets. A previous study proposed an efficient method for implementing the two-element Windkessel model to control the flow rate ratios at outlets. Here we clarify the general role of the resistance and capacitance in this approach and conduct a parametric sweep to examine how to choose their values for complex geometries. We show that the error of the flow rate ratios decreases exponentially as the resistance increases. The errors fall below 4% in a simple five-outlets model and 7% in a human artery model comprising ten outlets. Moreover, the flow rate ratios converge faster and suffer from weaker fluctuations as the capacitance decreases. Our findings also establish constraints on the parameters controlling the numerical stability of the simulations. The findings from this work are directly applicable to larger and more complex vascular domains encountered at full-human scale.
Determinants of timely initiation of complementary feeding among children aged 6–23 months in Ethiopia
Authors: Gilano Girma , Sako Sewunet , Gilano Kasarto
Published: November 2022

Introducing complementary feeding either early or later than 6 months is associated with future negative health outcomes. However, many women in Ethiopia do not follow WHO standard time to feed their children, which might be due to various demographic, economic, access, and availability of services. Thus, we aimed to identify factors attributing to the problems to assist future interventions. We used cross-sectional EMDHS 2019 for this analysis. We cleaned the data and 4061 women with under 2 years children were identified. We applied multilevel binary logistic regression in Stata v.15. Model comparison was based on log-likelihood ratio, deviance, and other criteria. We presented data using mean, percent, 95% CI, and adjusted odds ratio (AOR). The timely complementary feeding was 36.44% (34.93–37.92%). Factors like preceding birth intervals (AOR = 1.97 95% CI 1.62–1.39), primary education (AOR = 2.26 95% CI 1.40–3.62), secondary above education (AOR = 1.62 95% CI 1.10–2.38), and rich wealth index (AOR = 1.25 95% CI 1.03–1.52) were some of the associated factors. The magnitude of timely initiation of complementary feeding was diminutive. Authors suggest that interventions considering maternal education, empowering mothers economically, equity access to health services, and birth planning a good remedy.
Identification and validation of core genes as promising diagnostic signature in hepatocellular carcinoma based on integrated bioinformatics approach
Authors: Kumar Pradeep , Singh Amit Kumar , Tiwari Kavindra Nath , Mishra Sunil Kumar , Rajput Vishnu D. , Minkina Tatiana , Cavalu Simona , Pop Ovidiu
Published: November 2022

The primary objective of this investigation was to determine the hub genes of hepatocellular carcinoma (HCC) through an in silico approach. In the current context of the increased incidence of liver cancers, this approach could be a useful prognostic biomarker and HCC prevention target. This study aimed to examine hub genes for immune cell infiltration and their good prognostic characteristics for HCC research. Human genes selected from databases (Gene Cards and DisGeNET) were used to identify the HCC markers. Further, classification of the hub genes from communicating genes was performed using data derived from the targets' protein–protein interaction (PPI) platform. The expression as well as survival studies of all these selected genes were validated by utilizing databases such as GEPIA2, HPA, and immune cell infiltration. Based on the studies, five hub genes (TP53, ESR1, AKT1, CASP3, and JUN) were identified, which have been linked to HCC. They may be an important prognostic biomarker and preventative target of HCC. In silico analysis revealed that out of five hub genes, the TP53 and ESR1 hub genes potentially act as key targets for HCC prevention and treatment.
Temporal visual representation elicits early auditory-like responses in hearing but not in deaf individuals
Authors: Gori Monica , Amadeo Maria Bianca , Pavani Francesco , Valzolgher Chiara , Campus Claudio
Published: November 2022

It is evident that the brain is capable of large-scale reorganization following sensory deprivation, but the extent of such reorganization is to date, not clear. The auditory modality is the most accurate to represent temporal information, and deafness is an ideal clinical condition to study the reorganization of temporal representation when the audio signal is not available. Here we show that hearing, but not deaf individuals, show a strong ERP response to visual stimuli in temporal areas during a time-bisection task. This ERP response appears 50–90 ms after the flash and recalls some aspects of the N1 ERP component usually elicited by auditory stimuli. The same ERP is not evident for a visual space-bisection task, suggesting that the early recruitment of temporal cortex is specific for building a highly resolved temporal representation within the visual modality. These findings provide evidence that the lack of auditory input can interfere with typical development of complex visual temporal representations.
AQbD based green UPLC method to determine mycophenolate mofetil impurities and Identification of degradation products by QToF LCMS
Authors: Muchakayala Siva Krishna , Katari Naresh Kumar , Saripella Kalyan Kumar , Schaaf Henele , Marisetti Vishnu Murthy , Kowtharapu Leela Prasad , Jonnalagadda Sreekantha Babu
Published: November 2022

We report an ideal method for quantifying impurities in mycophenolate mofetil drug substances and their oral suspension preparations. We developed a systematic and eco-friendly analytical approach utilizing quality by design (QbD) and green chemistry principles. Initially, the critical method parameters (CMPs) were screened using a D-optimal design. The robust final method conditions were optimized using a systematic central composite design (CCD). Through graphical and numerical optimization, the protocol conditions were augmented. The pH of mobile phase buffer (25 mM KH2PO4) (MP-A), initial gradient composition (% MP-A), flow rate (mL min−1), and column oven temperatures (°C) are 4.05, 87, 0.4, and 30, respectively. The best possible separation between the critical pairs was achieved while using the Waters Acquity UPLC BEH C18 (100 × 2.1) mm, 1.7 µm analytical column. A mixture of water and acetonitrile in the ratio of 30:70 (v/v) was used as mobile phase-B for the gradient elution. The analytical method was validated in agreement with ICH and USP guidelines. The specificity results revealed that no peaks interfered with the impurities and MPM. The mean recovery of the impurities ranged between 96.2 and 102.7%, and the linearity results r > 0.999 across the range of LOQ – 150%. The precision results (%RSD) ranged between 0.8 and 4.5%. The degradation products formed during the base-induced degradation were identified as isomers of mycophenolic acid and sorbitol esters using Q-ToF LC–MS and their molecular and fragment ion peaks. The developed method eco-friendliness and greenness were assessed using analytical greenness (AGREE), green analytical procedure index (GAPI), and analytical eco score, and found it is green.
Multiacquisition with variable resonance image combination T2 (MAVRIC SL T2) for postoperative cervical spine with artificial disc replacement
Authors: Lee Ro Woon , Kim Yeo Ju , Yoon Daehyun , Lee Seunghun , Ryu Jeongah
Published: November 2022

Anterior cervical discectomy with artificial disc replacement (ADR) is an effective treatment of cervical degenerative disc disease. However, postoperative MRI due to recurrent neck/radicular pain is limited due to severe metallic artifacts of artificial disc instrument. Multiacquisition with variable resonance image combination selective T2 (MAVRIC SL T2) has been developed as an MRI technique for metal artifact reduction but has not been evaluated for the postoperative cervical spine with ADR. In our study, we compared MAVRIC SL T2 with the fast spin echo (FSE) T2-weighted sequence (T2WI), which was an essential MR sequence for evaluation of the cervical neural structure, for metallic artifact reduction in the post-operative cervical spine with ADR. Our study revealed MAVRIC SL T2 showed smaller signal void areas, less distortion and signal pile-up, and was more clinically useful than T2WI (p < 0.05). The spinal cord, vertebral bodies, both neural foramina, and anterior paravertebral soft tissue were significantly more visible with MAVRIC SL T2 than with T2WI (p < 0.05). MAVRIC SL T2 might be a useful technique for the evaluation of postoperative cervical spine with ADR and complements T2WI in the evaluation of the spinal cord and nerve roots which were important structures for post-operative recurrent neck/radicular pain.
Effect of out-of-village working activities on recent malaria exposure in the Peruvian Amazon using parametric g-formula
Authors: Carrasco-Escobar Gabriel , Rosado Jason , Nolasco Oscar , White Michael T. , Mueller Ivo , Castro Marcia C. , Rodriguez-Ferruci Hugo , Gamboa Dionicia , Llanos-Cuentas Alejandro , Vinetz Joseph M. , Benmarhnia Tarik
Published: November 2022

In the Amazon Region of Peru, occupational activities are important drivers of human mobility and may increase the individual risk of being infected while contributing to increasing malaria community-level transmission. Even though out-of-village working activities and other mobility patterns have been identified as determinants of malaria transmission, no studies have quantified the effect of out-of-village working activities on recent malaria exposure and proposed plausible intervention scenarios. Using two population-based cross-sectional studies in the Loreto Department in Peru, and the parametric g-formula method, we simulated various hypothetical scenarios intervening in out-of-village working activities to reflect their potential health benefits. This study estimated that the standardized mean outcome (malaria seroprevalence) in the unexposed population (no out-of-village workers) was 44.6% (95% CI: 41.7%–47.5%) and 66.7% (95% CI: 61.6%–71.8%) in the exposed population resulting in a risk difference of 22.1% (95% CI: 16.3%–27.9%). However, heterogeneous patterns in the effects of interest were observed between peri-urban and rural areas (Cochran’s Q test = 15.5, p < 0.001). Heterogeneous patterns were also observed in scenarios of increased prevalence of out-of-village working activities and restriction scenarios by gender (male vs. female) and age (18 and under vs. 19 and older) that inform possible occupational interventions targetting population subgroups. The findings of this study support the hypothesis that targeting out-of-village workers will considerably benefit current malaria elimination strategies in the Amazon Region. Particularly, males and adult populations that carried out out-of-village working activities in rural areas contribute the most to the malaria seropositivity (recent exposure to the parasite) in the Peruvian Amazon.
Genotyping-by-sequencing reveals range expansion of Adonis vernalis (Ranunculaceae) from Southeastern Europe into the zonal Euro-Siberian steppe
Authors: Seidl Anna , Tremetsberger Karin , Pfanzelt Simon , Lindhuber Lisa , Kropf Matthias , Neuffer Barbara , Blattner Frank R. , Király Gergely , Smirnov Sergey V. , Friesen Nikolai , Shmakov Alexander I. , Plenk Kristina , Batlai Oyuntsetseg , Hurka Herbert , Bernhardt Karl-Georg
Published: November 2022

The Euro-Siberian steppe flora consists of warm- and cold-adapted species, which may have responded differently to Pleistocene glacials and interglacials. Genotyping-by-sequencing individuals from across the distribution range of the pheasant’s eye (Adonis vernalis), we aimed to gain insight into steppe florogenesis based on the species’ evolutionary history. Although the primary area of origin of the species group comprising A. vernalis, A. villosa and A. volgensis is in Asia, our results indicate that recent populations of A. vernalis are not of Asian origin but evolved in the southern part of Europe during the Pleistocene, with Spanish populations clearly genetically distinct from the Southeastern European populations. We inferred that A. vernalis migrated eastwards from the sub-Mediterranean forest-steppes of Southeastern Europe into the continental forest-steppe zone. Eastern European populations had the highest private allelic richness, indicating long-term large population sizes in this region. As a thermophilic species, A. vernalis seems unlikely to have survived in the cold deserts of the Last Glacial Maximum in Western Siberia, so this region was likely (re)colonized postglacially. Overall, our results reinforce the importance of identifying the area of origin and the corresponding ecological requirements of steppe plants in order to understand the composition of today’s steppe flora.