bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivationale Handlungskonflikte zwischen Sport, Schule und Freizeit
Authors: Grassinger Robert , Weiß Kathrin , Daumiller Martin
Published: April 2023

Zusammenfassung: Die Theorie motivationaler Handlungskonflikte beschreibt das Erleben von Schule-Freizeit-Handlungskonflikten und der motivationalen Interferenz als Folge hiervon. Mit Blick auf sportlich aktive Kinder und Jugendliche wird erstmalig argumentiert, dass diese neben Schule-Freizeit- auch Schule-Sport- und Sport-Freizeit-Handlungskonflikte erleben und sich dies belastend auf die Ausführung der gewählten Handlungsoption auswirkt. Diese Annahme prüften wir mit 125 Schüler_innen (durchschnittliches Alter: 14.19, SD = 2.40, Jahre; 72 % weiblich), die wöchentlich durchschnittlich 5.50 Stunden ( SD = 2.36) trainierten. Die Befunde verweisen darauf, dass Schule-Sport- sowie Sport-Freizeit-Handlungskonflikte eigens zu betrachten sind. Hierbei erlebten die befragten Schüler_innen Schule-Freizeit- und Sport-Freizeit-Handlungskonflikte in ähnlichem Ausmaß, Schule-Sport-Handlungskonflikte hingegen signifikant seltener. Je mehr Zeit die Schüler_innen für ihre Sportart wöchentlich trainierten, desto ausgeprägter waren Schule-Sport-Handlungskonflikte sowie Sport-Freizeit-Handlungskonflikte. Schule-Sport-Handlungskonflikte waren assoziiert mit Belastungserleben bei schulischen Tätigkeiten, nicht hingegen mit Belastungserleben beim Sport. Explorativ zeigte sich, dass Schüler_innen mit höheren Wohlbefindenswerten sich bei motivationalen Konflikten eher für die sportliche Aktivität entscheiden.
The Meaning of School Grades and Self-Concept for General Self-Esteem in Secondary School Students
Authors: Henning Lena , Tietjens Maike , Dreiskämper Dennis
Published: April 2023

Abstract: This cross-sectional study with 825 students from fifth to ninth grade ( Mage = 13.01, SD = 1.30) investigated how self-concept domains (physical fitness and verbal) are associated with general self-esteem. Extending the internal/external frame of reference model, school grades in physical education and German (as a subject) were considered as correlates of the verbal and physical fitness self-concept domains. In addition, considering the well-established empirical evidence on gender differences in the different subdomains, measurement and structural invariance were tested across female and male students. Grades, self-concept, and self-esteem were assessed via questionnaires. Structural equation modeling revealed positive relations between grades and the corresponding self-concept subdomains. Physical self-concept had a stronger association with general self-esteem compared with verbal self-concept. Gender stereotypical differences were found only in the mean values of self-concept subdomains and general self-esteem. The results indicate that school grades and the corresponding self-concepts are strongly associated and that physical self-concept might be a salient and meaningful source of general self-esteem in adolescents.
Kiasu (Fear of Losing Out)
Authors: Cheng Chi-Ying , Wee Sheila X. R.
Published: April 2023

Abstract: “Kiasu,” a Hokkien term, which directly translates as the “fear of losing out” is synonymous with the Singapore identity. Yet, there has been little empirical research investigating this indigenous psychological construct in Singapore. This paper first delves into Singapore’s Kiasu culture and existing research of Kiasu, which diverges on the operationalization and measurement of Kiasu as a psychological construct. While early research conceptualized Kiasu as a behavioral tendency, more recent investigations have begun to construe Kiasu as a mindset. Next, we review Kiasu-related outcomes in four domains: academic performance, learning strategies, well-being, and creativity. Finally, we propose a new theoretical framework integrating current research to guide future research directions. Specifically, the proposed integrated model is composed of Kiasu antecedents, individual Kiasu mindset, Kiasu behaviors, and Kiasu outcomes with moderators of normative Kiasu mindset and incentive system in the context. We believe that this proposed integrated model will help us better understand the prevalent Kiasu mindset and behavior in Singapore.
Felt Reports Could Shake Up Earthquake Response
Authors: Sidik Saima
Published: April 2023

Firsthand accounts of earthquake impacts could aid in identifying people who require help as well as increasing safety in some areas.
PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability
Authors: Martínez Natalia , Gragera Teresa , de Lucas María Pilar , Cámara Ana Belén , Ballester Alicia , Anta Berta , Fernández-Medarde Alberto , López-Briones Tania , Ortega Judith , Peña-Jiménez Daniel , Barbáchano Antonio , Montero-Calle Ana , Cordero Víctor , Barderas Rodrigo , Iglesias Teresa , Yunta Mónica , Oliva José Luís , Muñoz Alberto , Santos Eugenio , Zarich Natasha , Rojas-Cabañeros José M.
Published: April 2023

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.
Mutation-induced infections of phage-plasmids
Authors: Shan Xiaoyu , Szabo Rachel E. , Cordero Otto X.
Published: April 2023

Phage-plasmids are extra-chromosomal elements that act both as plasmids and as phages, whose eco-evolutionary dynamics remain poorly constrained. Here, we show that segregational drift and loss-of-function mutations play key roles in the infection dynamics of a cosmopolitan phage-plasmid, allowing it to create continuous productive infections in a population of marine Roseobacter. Recurrent loss-of-function mutations in the phage repressor that controls prophage induction leads to constitutively lytic phage-plasmids that spread rapidly throughout the population. The entire phage-plasmid genome is packaged into virions, which were horizontally transferred by re-infecting lysogenized cells, leading to an increase in phage-plasmid copy number and to heterozygosity in a phage repressor locus in re-infected cells. However, the uneven distribution of phage-plasmids after cell division (i.e., segregational drift) leads to the production of offspring carrying only the constitutively lytic phage-plasmid, thus restarting the lysis-reinfection-segregation life cycle. Mathematical models and experiments show that these dynamics lead to a continuous productive infection of the bacterial population, in which lytic and lysogenic phage-plasmids coexist. Furthermore, analyses of marine bacterial genome sequences indicate that the plasmid backbone here can carry different phages and disseminates trans-continentally. Our study highlights how the interplay between phage infection and plasmid genetics provides a unique eco-evolutionary strategy for phage-plasmids.
Unintended cation crossover influences CO2 reduction selectivity in Cu-based zero-gap electrolysers
Authors: El-Nagar Gumaa A. , Haun Flora , Gupta Siddharth , Stojkovikj Sasho , Mayer Matthew T.
Published: April 2023

Membrane electrode assemblies enable CO2electrolysis at industrially relevant rates, yet their operational stability is often limited by formation of solid precipitates in the cathode pores, triggered by cation crossover from the anolyte due to imperfect ion exclusion by anion exchange membranes. Here we show that anolyte concentration affects the degree of cation movement through the membranes, and this substantially influences the behaviors of copper catalysts in catholyte-free CO2electrolysers. Systematic variation of the anolyte (KOH or KHCO3) ionic strength produced a distinct switch in selectivity between either predominantly CO or C2+products (mainly C2H4) which closely correlated with the quantity of alkali metal cation (K+) crossover, suggesting cations play a key role in C-C coupling reaction pathways even in cells without discrete liquid catholytes. Operando X-ray absorption and quasi in situ X-ray photoelectron spectroscopy revealed that the Cu surface speciation showed a strong dependence on the anolyte concentration, wherein dilute anolytes resulted in a mixture of Cu+and Cu0surface species, while concentrated anolytes led to exclusively Cu0under similar testing conditions. These results show that even in catholyte-free cells, cation effects (including unintentional ones) significantly influence reaction pathways, important to consider in future development of catalysts and devices.
The impact of land use on non-native species incidence and number in local assemblages worldwide
Authors: Liu Daijun , Semenchuk Philipp , Essl Franz , Lenzner Bernd , Moser Dietmar , Blackburn Tim M. , Cassey Phillip , Biancolini Dino , Capinha César , Dawson Wayne , Dyer Ellie E. , Guénard Benoit , Economo Evan P. , Kreft Holger , Pergl Jan , Pyšek Petr , van Kleunen Mark , Nentwig Wolfgang , Rondinini Carlo , Seebens Hanno , Weigelt Patrick , Winter Marten , Purvis Andy , Dullinger Stefan
Published: April 2023

While the regional distribution of non-native species is increasingly well documented for some taxa, global analyses of non-native species in local assemblages are still missing. Here, we use a worldwide collection of assemblages from five taxa - ants, birds, mammals, spiders and vascular plants - to assess whether the incidence, frequency and proportions of naturalised non-native species depend on type and intensity of land use. In plants, assemblages of primary vegetation are least invaded. In the other taxa, primary vegetation is among the least invaded land-use types, but one or several other types have equally low levels of occurrence, frequency and proportions of non-native species. High land use intensity is associated with higher non-native incidence and frequency in primary vegetation, while intensity effects are inconsistent for other land-use types. These findings highlight the potential dual role of unused primary vegetation in preserving native biodiversity and in conferring resistance against biological invasions.
Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla
Authors: Lucas Beth , White Andrea J. , Klein Fabian , Veiga-Villauriz Clara , Handel Adam , Bacon Andrea , Cosway Emilie J. , James Kieran D. , Parnell Sonia M. , Ohigashi Izumi , Takahama Yousuke , Jenkinson William E. , Hollander Georg A. , Lu Wei-Yu , Anderson Graham
Published: April 2023

The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.
Seismic magnitude clustering is prevalent in field and laboratory catalogs
Authors: Xiong Q. , Brudzinski M. R. , Gossett D. , Lin Q. , Hampton J. C.
Published: April 2023

Clustering of earthquake magnitudes is still actively debated, compared to well-established spatial and temporal clustering. Magnitude clustering is not currently implemented in earthquake forecasting but would be important if larger magnitude events are more likely to be followed by similar sized events. Here we show statistically significant magnitude clustering present in many different field and laboratory catalogs at a wide range of spatial scales (mm to 1000 km). It is universal in field catalogs across fault types and tectonic/induced settings, while laboratory results are unaffected by loading protocol or rock types and show temporal stability. The absence of clustering can be imposed by a global tensile stress, although clustering still occurs when isolating to triggered event pairs or spatial patches where shear stress dominates. Magnitude clustering is most prominent at short time and distance scales and modeling indicates >20% repeating magnitudes in some cases, implying it can help to narrow physical mechanisms for seismogenesis.
Widespread global disparities between modelled and observed mid-depth ocean currents
Authors: Su Fenzhen , Fan Rong , Yan Fengqin , Meadows Michael , Lyne Vincent , Hu Po , Song Xiangzhou , Zhang Tianyu , Liu Zenghong , Zhou Chenghu , Pei Tao , Yang Xiaomei , Du Yunyan , Wei Zexun , Wang Fan , Qi Yiquan , Chai Fei
Published: April 2023

The mid-depth ocean circulation is critically linked to actual changes in the long-term global climate system. However, in the past few decades, predictions based on ocean circulation models highlight the lack of data, knowledge, and long-term implications in climate change assessment. Here, using 842,421 observations produced by Argo floats from 2001-2020, and Lagrangian simulations, we show that only 3.8% of the mid-depth oceans, including part of the equatorial Pacific Ocean and the Antarctic Circumpolar Current, can be regarded as accurately modelled, while other regions exhibit significant underestimations in mean current velocity. Knowledge of ocean circulation is generally more complete in the low-latitude oceans but is especially poor in high latitude regions. Accordingly, we propose improvements in forecasting, model representation of stochasticity, and enhancement of observations of ocean currents. The study demonstrates that knowledge and model representations of global circulation are substantially compromised by inaccuracies of significant magnitude and direction, with important implications for modelled predictions of currents, temperature, carbon dioxide sequestration, and sea-level rise trends.
Stretchable array electromyography sensor with graph neural network for static and dynamic gestures recognition system
Authors: Lee Hyeyun , Lee Soyoung , Kim Jaeseong , Jung Heesoo , Yoon Kyung Jae , Gandla Srinivas , Park Hogun , Kim Sunkook
Published: April 2023

With advances in artificial intelligence (AI)-based algorithms, gesture recognition accuracy from sEMG signals has continued to increase. Spatiotemporal multichannel-sEMG signals substantially increase the quantity and reliability of the data for any type of study. Here, we report an array of bipolar stretchable sEMG electrodes with a self-attention-based graph neural network to recognize gestures with high accuracy. The array is designed to spatially cover the skeletal muscles to acquire the regional sampling data of EMG activity from 18 different gestures. The system can differentiate individual static and dynamic gestures with ~97% accuracy when training a single trial per gesture. Moreover, a sticky patchwork of holes adhered to an array sensor enables skin-like attributes such as stretchability and water vapor permeability and aids in delivering stable EMG signals. In addition, the recognition accuracy (~95%) remained unchanged even after long-term testing for over 72 h and being reused more than 10 times.
OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans
Authors: Viviani Viola , Fantoni Adele , Tomei Sara , Marchi Sara , Luzzi Enrico , Bodini Margherita , Muzzi Alessandro , Giuliani Marzia M. , Maione Domenico , Derrick Jeremy P. , Delany Isabel , Pizza Mariagrazia , Biolchi Alessia , Bartolini Erika
Published: April 2023

The ability ofNeisseria meningitidisOuter Membrane Vesicles (OMV) to induce protective responses in humans is well established and mainly attributed to Porin A (PorA). However, the contribution of additional protein antigens to protection remains to be elucidated. In this study we dissected the immunogenicity of antigens originating from the OMV component of the 4CMenB vaccine in mice and humans. We collected functional data on a panel of strains for which bactericidal responses to 4CMenB in infants was attributable to the OMV component and evaluated the role of 30 OMV-specific protein antigens in cross-coverage. By using tailor-made protein microarrays, the immunosignature of OMV antigens was determined. Three of these proteins, OpcA, NspA, and PorB, triggered mouse antibodies that were bactericidal against severalN. meningitidisstrains. Finally, by genetic deletion and/or serum depletion studies, we demonstrated the ability of OpcA and PorB to induce functional immune responses in infant sera after vaccination. In conclusion, while confirming the role of PorA in eliciting protective immunity, we identified two OMV antigens playing a key role in protection of infants vaccinated with the 4CMenB vaccine against differentN. meningitidisserogroup B strains.
Dynamic synchronization between hippocampal representations and stepping
Authors: Joshi Abhilasha , Denovellis Eric L. , Mankili Abhijith , Meneksedag Yagiz , Davidson Thomas J. , Gillespie Anna K. , Guidera Jennifer A. , Roumis Demetris , Frank Loren M.
Published: April 2023

The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4–7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8–11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground (‘plant’ times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory–motor circuits.
Extrachromosomal DNA in the cancerous transformation of Barrett’s oesophagus
Authors: Luebeck Jens , Ng Alvin Wei Tian , Galipeau Patricia C. , Li Xiaohong , Sanchez Carissa A. , Katz-Summercorn Annalise C. , Kim Hoon , Jammula Sriganesh , He Yudou , Lippman Scott M. , Verhaak Roel G. W. , Maley Carlo C. , Alexandrov Ludmil B. , Reid Brian J. , Fitzgerald Rebecca C. , Paulson Thomas G. , Chang Howard Y. , Wu Sihan , Bafna Vineet , Mischel Paul S.
Published: April 2023

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1–6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett’s oesophagus. These data included 206 biopsies in Barrett’s oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case–control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett’s-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.
MicroRNA-142-3p promotes renal cell carcinoma progression by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways
Authors: Zhang Yijing , Ma Sha , Zhang Jun , Lou Lu , Liu Wanqi , Gao Chao , Miao Long , Sun Fanghao , Chen Wei , Cao Xiliang , Wei Jin
Published: April 2023

MicroRNAs play a critical regulatory role in different cancers, but their functions in renal cell carcinoma (RCC) have not been elucidated. Reportedly, miR-142-3p is involved in the tumorigenesis and the development of RCC in vitro and is clinically correlated with the poor prognosis of RCC patients. However, the molecular target of miR-142-3p and the underlying mechanism are unclear. In this study, we found that miR-142-3p was upregulated in RCC tumor tissues and downregulated in exosomes compared to normal tissues. The expression of miR-142-3p was inversely associated with the survival of patients with kidney renal clear cell carcinoma (KIRC). RhoBTB3 was reduced in RCC, and miR-142-3p plays an inverse function with RhoBTB3 in KIRC. The direct interaction between RhoBTB3 and miR-142-3p was demonstrated by a dual luciferase reporter assay. miR-142-3p promoted metastasis in the xenograft model, and the suppression of miR-142-3p upregulated RhoBTB3 protein expression and inhibited the mRNAs and proteins of HIF1A, VEGFA, and GGT1. Also, the miR-142-3p overexpression upregulated the mRNA of HIF1A, VEGFA, and GGT1. In conclusion, miR-142-3p functions as an oncogene in RCC, especially in KIRC, by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways, which needs further exploration.
Facial emotion recognition in patients with depression compared to healthy controls when using human avatars
Authors: Monferrer Marta , García Arturo S. , Ricarte Jorge J. , Montes María J. , Fernández-Caballero Antonio , Fernández-Sotos Patricia
Published: April 2023

The negative, mood-congruent cognitive bias described in depression, as well as excessive rumination, have been found to interfere with emotional processing. This study focuses on the assessment of facial recognition of emotions in patients with depression through a new set of dynamic virtual faces (DVFs). The sample consisted of 54 stable patients compared to 54 healthy controls. The experiment consisted in an emotion recognition task using non-immersive virtual reality (VR) with DVFs of six basic emotions and neutral expression. Patients with depression showed a worst performance in facial affect recognition compared to healthy controls. Age of onset was negatively correlated with emotion recognition and no correlation was observed for duration of illness or number of lifetime hospitalizations. There was no correlation for the depression group between emotion recognition and degree of psychopathology, excessive rumination, degree of functioning, or quality of life. Hence, it is important to improve and validate VR tools for emotion recognition to achieve greater methodological homogeneity of studies and to be able to establish more conclusive results.
Outpatient clinic specific for end-stage renal disease improves patient survival rate after initiating dialysis
Authors: Fukuzaki Haruna , Nakata Junichiro , Nojiri Shuko , Shimizu Yuki , Shirotani Yuka , Maeda Takuya , Kano Toshiki , Mishiro Maiko , Nohara Nao , Io Hiroaki , Suzuki Yusuke
Published: April 2023

The importance of a shared decision-making (SDM) approach is widely recognized worldwide. In Japan, hospital accreditation involves the promotion of SDM for patients with end-stage renal disease (ESRD) when considering renal replacement therapy (RRT). This study aimed to clarify the effectiveness and long-term medical benefits of SDM in RRT. Patients with ESRD who underwent dialysis therapy were retrospectively divided into those who visited outpatient clinics specific for ESRD (ESRD clinic) supporting RRT selection with an SDM approach (visited group) and those who did not visit the ESRD clinic (non-visited group). Data of 250 patients (129 in the non-visited group and 121 in the visited group) were analyzed. Mortality was significantly higher in the non-visited group than in the visited group. Not seeing an ESRD specialist was associated with emergent initiation of dialysis and subsequent 1 year mortality. The number of patients who chose peritoneal dialysis as a modality of RRT was significantly larger in the visited group. These findings demonstrate the association between the ESRD clinic, 1 year survival in patients with ESRD after initiating dialysis, and the different RRT modalities. This specific approach in the ESRD clinic may improve the management of patients with ESRD.
Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer
Authors: Hatcher Charlie , Richenberg George , Waterson Samuel , Nguyen Long H. , Joshi Amit D. , Carreras-Torres Robert , Moreno Victor , Chan Andrew T. , Gunter Marc , Lin Yi , Qu Conghui , Song Mingyang , Casey Graham , Figueiredo Jane C. , Gruber Stephen B. , Hampe Jochen , Hampel Heather , Jenkins Mark A. , Keku Temitope O. , Peters Ulrike , Tangen Catherine M. , Wu Anna H. , Hughes David A. , Rühlemann Malte C. , Raes Jeroen , Timpson Nicholas J. , Wade Kaitlin H.
Published: April 2023

The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
Association between soluble angiotensin-converting enzyme 2 in saliva and SARS-CoV-2 infection: a cross-sectional study
Authors: Bru Samuel , Brotons Pedro , Jordan Iolanda , Alsina Laia , Henares Desiree , Carballar Reyes , de Sevilla Mariona Fernandez , Barrabeig Irene , Fumado Victoria , Baro Bàrbara , Martínez-Láinez Joan Marc , Garcia-Garcia Juan J. , Bassat Quique , Balaguer Albert , Clotet Josep , Launes Cristian , Muñoz-Almagro Carmen
Published: April 2023

This study aimed to investigate the association between saliva soluble angiotensin-converting enzyme 2 (sACE2) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adults. We selected a convenience sample of adults with post-acute SARS-CoV-2 infection and their household children living in quarantined family households of the metropolitan Barcelona region (Spain) during the spring 2020 pandemic national lockdown. Participants were tested for saliva sACE2 quantification by western blot and nasopharyngeal SARS-CoV-2 RT-PCR detection. A total of 161 saliva samples [82 (50.9%) from children; 79 (49.1%) from females] yielded valid western blot and RT-PCR results. Saliva sACE2 was detected in 79 (96.3%) children and 76 (96.2%) convalescent adults. Twenty (24.4%) children and 20 (25.3%) convalescent adults were positive for SARS-CoV-2 in nasopharynx by RT-PCR. SARS-CoV-2 RT-PCR-negative children had a significantly higher mean proportional level of saliva sACE2 (0.540 × 10–3%) than RT-PCR-positive children (0.192 × 10–3%, p < 0.001) and convalescent adults (0.173 × 10–3%, p < 0.001). In conclusion, children negative for nasopharyngeal SARS-CoV-2 RT-PCR appear to exhibit a higher concentration of saliva sACE2 than SARS-CoV-2 RT-PCR-positive children and convalescent adults. Release of adequate levels of sACE2 in saliva could play a protective role against SARS-CoV-2.
Factors hindering coverage of targeted mass treatment with primaquine in a malarious township of northern Myanmar in 2019–2020
Authors: Aung Pyae Linn , Soe Myat Thu , Soe Than Naing , Oo Thit Lwin , Win Kyawt Mon , Cui Liwang , Kyaw Myat Phone , Sattabongkot Jetsumon , Okanurak Kamolnetr , Parker Daniel M.
Published: April 2023

Targeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation.
Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury
Authors: Jo Seongmoon , Baek Ahreum , Cho Yoonhee , Kim Sung Hoon , Baek Dawoon , Hwang Jihye , Cho Sung-Rae , Kim Hyun Jung
Published: April 2023

Polydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.
Rapid multi-criterial design of microwave components with robustness analysis by means of knowledge-based surrogates
Authors: Koziel Slawomir , Pietrenko-Dabrowska Anna
Published: April 2023

Manufacturing tolerances and uncertainties concerning material parameters, e.g., operating conditions or substrate permittivity are detrimental to characteristics of microwave components. The knowledge of relations between acceptable parameter deviations (not leading to violation of design specifications) and the nominal performance (not considering uncertainties), and is therefore indispensable. This paper proposes a multi-objective optimization technique of microwave components with tolerance analysis. The goal is to identify a set of trade-off designs: nominal performance versus robustness (quantified by the maximum input tolerance values that allow for achieving 100-percent fabrication yield). Our approach exploits knowledge-driven regression predictors rendered using characteristic points (features) of the component’s response for a rapid evaluation of statistical performance figures, along with trust-region algorithm to enable low execution cost as well as convergence. The proposed methodology is verified with the use of three microstrip circuits, a broadband filter, and two branch-line couplers (a single- and a dual-band one). It is demonstrated that a Pareto set w.r.t. nominal performance and robustness objectives can be produced using only 40 to 60 EM simulations of the respective structure (per design). Reliability of the proposed algorithm is corroborated with the use of EM-based Monte Carlo simulation.
Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats
Authors: Abd-Elhakim Yasmina M. , Behairy Amany , Hashem Mohamed M. M. , Abo-EL-Sooud Khaled , El-Metwally Abeer E. , Hassan Bayan A. , Ali Haytham A.
Published: April 2023

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production.
Transgene-induced cell death following dengue-2 virus infection in Aedes aegypti
Authors: Carvalho Danilo O. , Costa-da-Silva Andre L. , Petersen Vivian , de Souza Micael Santana , Ioshino Rafaella S. , Marques Isabel C. S. , Franz Alexander W. E. , Olson Ken E. , James Anthony A. , Capurro Margareth L.
Published: April 2023

Dengue viruses (DENVs) are mosquito-borne flaviviruses causing millions of human infections each year and pose a challenge for public health systems worldwide.Aedes aegyptiis the principal vector species transmitting DENVs to humans. ControllingAe. aegyptiis difficult due to the abundance of breeding sites and increasing insecticide resistance in the vector populations. Developing new vector control strategies is critical for decreasing the disease burden. One potential approach is genetically replacingAe. aegyptipopulations with vector populations highly resistant to DENV transmission. Here, we focus on an alternative strategy for generating dengue 2 virus (DENV-2) resistance in genetically-modifiedAe. aegyptiin which the mosquitoes express an inactive form of Michelob_x (Mx), an antagonist of the Inhibitor of Apoptosis (IAP), to induce apoptosis in those cells in which actively replicating DENV-2 is present. The inactive form of Mx was flanked by the RRRRSAG cleavage motif, which was recognized by the NS2B/NS3 protease of the infecting DENV-2 thereby releasing and activating Mx which then induced apoptosis. Our transgenic strain exhibited a significantly higher mortality rate than the non-transgenic control when infected with DENV-2. We also transfected a DNA construct containing inactive Mx fused to eGFP into C6/36 mosquito cells and indirectly observed Mx activation on days 3 and 6 post-DENV-2 infections. There were clear signs that the viral NS2B/NS3 protease cleaved the transgene, thereby releasing Mx protein into the cytoplasm, as was confirmed by the detection of eGFP expression in infected cells. The present study represents proof of the concept that virus infection can be used to induce apoptosis in infected mosquito cells.
Association between social jetlag and chronic kidney disease among the Korean working population
Authors: Cho Seong-Sik , Chung Byung Ha , Lee Hye-Eun , Kang Mo-Yeol
Published: April 2023

Social jetlag refers to the discrepancy between social time and the body’s internal rhythm, which can lead to unfavorable health outcomes. However, no study has directly explored the relation between social jetlag and chronic kidney disease (CKD). This study aims to investigate the relationship between social jetlag and CKD in a representative population of South Korea. This study included 8259 currently economically active Korean population in the Korea National Health and Nutrition Examination Survey. Social jetlag was calculated as the difference between the midpoint of sleep time on weekdays and free days. The estimated glomerular filtration rate (eGFR) was calculated the by using the serum creatinine value according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Participants with an eGFR less than 60 ml/min/1.73 m2 were defined as CKD cases. The estimated glomerular filtration rate decreased as social jetlag increased. Multiple logistic regression analysis showed that the adjusted odds ratio (95% confidence interval) of CKD for 1–2 h of social jetlag was 0.926 (0.660–1.299), while the odds ratio for more than 2 h was 2.042 (1.328–3.139) when less than 1 h was used as reference. This study found that social jetlag and risk of CKD were significantly related in the Korean working population.
Stronger functional connectivity during reading contextually predictable words in slow readers
Authors: Weiss Kim-Lara , Hawelka Stefan , Hutzler Florian , Schuster Sarah
Published: April 2023

The effect of word predictability is well-documented in terms of local brain activation, but less is known about the functional connectivity among those regions associated with processing predictable words. Evidence from eye movement studies showed that the effect is much more pronounced in slow than in fast readers, suggesting that speed-impaired readers rely more on sentence context to compensate for their difficulties with visual word recognition. The present study aimed to investigate differences in functional connectivity of fast and slow readers within core regions associated with processing predictable words. We hypothesize a stronger synchronization between higher-order language areas, such as the left middle temporal (MTG) and inferior frontal gyrus (IFG), and the left occipito-temporal cortex (OTC) in slow readers. Our results show that slow readers exhibit more functional correlations among these connections; especially between the left IFG and OTC. We interpret our results in terms of the lexical quality hypothesis which postulates a stronger involvement of semantics on orthographic processing in (speed-)impaired readers.
Explainable artificial intelligence incorporated with domain knowledge diagnosing early gastric neoplasms under white light endoscopy
Authors: Dong Zehua , Wang Junxiao , Li Yanxia , Deng Yunchao , Zhou Wei , Zeng Xiaoquan , Gong Dexin , Liu Jun , Pan Jie , Shang Renduo , Xu Youming , Xu Ming , Zhang Lihui , Zhang Mengjiao , Tao Xiao , Zhu Yijie , Du Hongliu , Lu Zihua , Yao Liwen , Wu Lianlian , Yu Honggang
Published: April 2023

White light endoscopy is the most pivotal tool for detecting early gastric neoplasms. Previous artificial intelligence (AI) systems were primarily unexplainable, affecting their clinical credibility and acceptability. We aimed to develop an explainable AI named ENDOANGEL-ED (explainable diagnosis) to solve this problem. A total of 4482 images and 296 videos with focal lesions from 3279 patients from eight hospitals were used for training, validating, and testing ENDOANGEL-ED. A traditional sole deep learning (DL) model was trained using the same dataset. The performance of ENDOANGEL-ED and sole DL was evaluated on six levels: internal and external images, internal and external videos, consecutive videos, and man–machine comparison with 77 endoscopists in videos. Furthermore, a multi-reader, multi-case study was conducted to evaluate the ENDOANGEL-ED’s effectiveness. A scale was used to compare the overall acceptance of endoscopists to traditional and explainable AI systems. The ENDOANGEL-ED showed high performance in the image and video tests. In man–machine comparison, the accuracy of ENDOANGEL-ED was significantly higher than that of all endoscopists in internal (81.10% vs. 70.61%, p < 0.001) and external videos (88.24% vs. 78.49%, p < 0.001). With ENDOANGEL-ED’s assistance, the accuracy of endoscopists significantly improved (70.61% vs. 79.63%, p < 0.001). Compared with the traditional AI, the explainable AI increased the endoscopists’ trust and acceptance (4.42 vs. 3.74, p < 0.001; 4.52 vs. 4.00, p < 0.001). In conclusion, we developed a real-time explainable AI that showed high performance, higher clinical credibility, and acceptance than traditional DL models and greatly improved the diagnostic ability of endoscopists.
No apparent trade-offs associated with heat tolerance in a reef-building coral
Authors: Lachs Liam , Humanes Adriana , Pygas Daniel R. , Bythell John C. , Mumby Peter J. , Ferrari Renata , Figueira Will F. , Beauchamp Elizabeth , East Holly K. , Edwards Alasdair J. , Golbuu Yimnang , Martinez Helios M. , Sommer Brigitte , van der Steeg Eveline , Guest James R.
Published: April 2023

As marine species adapt to climate change, their heat tolerance will likely be under strong selection. Yet trade-offs between heat tolerance and other life history traits could compromise natural adaptation or assisted evolution. This is particularly important for ecosystem engineers, such as reef-building corals, which support biodiversity yet are vulnerable to heatwave-induced mass bleaching and mortality. Here, we exposed 70 colonies of the reef-building coral Acropora digitifera to a long-term marine heatwave emulation experiment. We tested for trade-offs between heat tolerance and three traits measured from the colonies in situ – colony growth, fecundity, and symbiont community composition. Despite observing remarkable within-population variability in heat tolerance, all colonies were dominated by Cladocopium C40 symbionts. We found no evidence for trade-offs between heat tolerance and fecundity or growth. Contrary to expectations, positive associations emerged with growth, such that faster-growing colonies tended to bleach and die at higher levels of heat stress. Collectively, our results suggest that these corals exist on an energetic continuum where some high-performing individuals excel across multiple traits. Within populations, trade-offs between heat tolerance and growth or fecundity may not be major barriers to natural adaptation or the success of assisted evolution interventions.