bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of inoculation methods for the assessment of bacterial halo blight in coffee seedlings
Authors: Oliveira J. M. , Pozza E. A. , Belan L. L. , Freitas M. L. O. , Tedardi V. M.
Published: June 2024

Bacterial halo blight (BHB), caused byPseudomonas coronafacienspv.garcae(Pcg), is one of the most significant diseases affecting coffee trees worldwide, resulting in considerable damage and notable losses within coffee production systems. Further research into the epidemiology and aetiology of BHB in coffee plants is essential for developing effective management strategies. Understanding the efficiency of each inoculation methodology in inducing symptoms is crucial for advancing this research. Therefore, this study aimed to assess the efficiency of seven Pcg inoculation methods using five concentrations to enhance the highest BHB intensity. The experimental design was a complete randomized block design in a factorial (7 × 5) variance analysis with four replications. The first three pairs of leaves of coffee seedlings of the cultivar Catuaí Vermelho IAC‐99 were inoculated and evaluated for the incidence and severity of BHB. The inoculation methods of Pcg by injury provided higher BHB AUDPCI and AUDPCS values. Among these, the inoculum injection and multi‐needle wounding at inoculum concentrations of 1.6 × 109 CFU mL−1demonstrated higher disease intensity.
Facial Mimicry in Unstructured Dyadic Interactions: A Cross‐Cultural Study
Authors: Chuang Yi‐Chun , Fujiwara Ken
Published: June 2024

Facial mimicry, known as the tendency to imitate other individuals' facial muscular movements, is key to establishing successful interpersonal relationships. Studies on various cultures have confirmed this tendency, suggesting that facial mimicry is a universal behavioral pattern in interpersonal communication. However, its cross‐cultural variability is expected because of the influence of cultural norms regarding facial expressions. By focusing on unstructured dyadic interactions, we addressed the unexplored cross‐cultural variability of facial mimicry through a secondary analysis of video data obtained in Japan and Spain and a further analysis of newly collected videos in Taiwan. We also explored the association between the Big Five personality traits and facial mimicry cross‐culturally. To measure facial mimicry, the intensity of each facial action unit movement was quantified using OpenFace, which underwent multidimensional dynamic time warping. First, employing the pseudo‐synchrony paradigm of random data shuffling, we confirmed that interactants displayed facial mimicry beyond chance during their conversation. Second, we found that the extent of mimicry was significantly different among the three cultures; that is, interactants from East Asian cultures (Taiwan, Japan) showed a greater extent of mimicry than those from Western cultures (Spain) even after controlling for unbalanced gender composition in the data. Third, conscientiousness was significantly associated with the degree of mimicry. However, the association between personality traits and mimicry was not consistent across cultures. Overall, this study discusses the importance of cross‐cultural research in facial mimicry, as in the study of facial expressions.
The Effects of Adding Emojis to Text Messages on Emotional Impressions and Recollection of Textual Content
Authors: Suzuki Momoka , Ujiie Yuta , Takahashi Kohske
Published: June 2024

Emojis or emoticons are commonly used to convey emotional status to others in text‐based, online communication. While several studies have investigated the influence of emojis on emotional processing, the influence of emojis on the recognition of messages is less understood. In the present study, we investigated the effects of emojis accompanying a short text message on the emotional impressions and memory of the messages. The results suggested that emojis modulated the emotional processing of the messages; the emotional arousal of the messages increased by adding emojis, and the emotional valence of messages was biased towards the valence of emojis. Furthermore, we found that the memory of the text messages was modulated by emojis; the recognition performance of the positive text messages was improved when they appeared with negative emojis. These results implied that emojis would have an impact on cognitive processing, as well as the emotional processing of text messages.
Do the Three Modern Social Conditions—High Existential Security, Education, and Urbanicity—Really Make People Less Religious? A Worldwide Analysis, 1989–2020
Authors: Roberts Louisa L.
Published: June 2024

Some versions of secularization theory propose that existential security, education, and urbanicity exert directly measurable negative effects on religiosity cross‐culturally. However, few studies have tested this using longitudinal data. Nor have researchers adequately examined how much the relationship between these modern social conditions (MSCs) and religiosity varies society‐to‐society. This study addresses these limitations in a series of new analyses, using 1989–2020 World/European Values Survey data from approximately 100 countries. Results suggest that the three MSCs do not exert independent, negative effects on religiosity in general, at least not in the short or medium term. Indeed, national‐average increases in these MSCs were not found to predict decreased religiosity. And, interestingly and unexpectedly, the direction of individual‐level relationships between each MSC and religiosity varied greatly between countries and world regions. These findings suggest scholars should probably look elsewhere to explain why average religiosity has decreased in some world locations over recent decades.
Far‐red light increases maize volatile emissions in response to volatile cues from neighbouring plants
Authors: Escobar‐Bravo Rocío , Schimmel Bernardus C. J. , Zhang Yaqin , Wang Lei , Robert Christelle A. M. , Glauser Gaétan , Ballaré Carlos L. , Erb Matthias
Published: June 2024

Plants perceive the presence and defence status of their neighbours through light and volatile cues, but how plants integrate both stimuli is poorly understood. We investigated if and how low Red to Far red light (R:FR) ratios, indicative of shading or canopy closure, affect maize (Zea mays) responses to herbivore‐induced plant volatiles (HIPVs), including the green leaf volatile (Z)−3‐hexenyl acetate. We modulated light signalling and perception by using FR supplementation and a phyB1phyB2 mutant, and we determined volatile release as a response readout. To gain mechanistic insights, we examined expression of volatile biosynthesis genes, hormone accumulation, and photosynthesis. Exposure to a full blend of HIPVs or (Z)−3‐hexenyl acetate induced maize volatile release. Short‐term FR supplementation increased this response. In contrast, prolonged FR supplementation or constitutive phytochrome B inactivation in phyB1phyB2 plants showed the opposite response. Short‐term FR supplementation enhanced photosynthesis and stomatal conductance and (Z)−3‐hexenyl acetate‐induced JA‐Ile levels. We conclude that a FR‐enriched light environment can prompt maize plants to respond more strongly to HIPVs emitted by neighbours, which might be explained by changes in photosynthetic processes and phytochrome B signalling. Our findings reveal interactive responses to light and volatile cues with potentially important consequences for plant‐plant and plant‐herbivore interactions.
Acoustic communication in bark beetles (Scolytinae): 150 years of research
Authors: Arjomandi Elham , Turchen Leonardo M. , Connolly Amanda A. , Léveillée Michelle B. , Yack Jayne E.
Published: June 2024

For over a century, the role of acoustic communication in the sensory ecology of bark beetles (Scolytinae) has been recognized. However, their ‘world of sound’ remains largely unexplored. Here, we review 153 years of bark beetle bioacoustics publications to summarize current knowledge, identify gaps and suggest future research directions. Our survey identified 117 publications covering 170 species. Morphological reports revealed five stridulatory organs across 125 species, with elytro‐tergal, gular‐prosternal and vertex‐pronotum mechanisms being the most prevalent for sound production. However, confirmed sound recordings exist for only 40 species. Acoustic signalling in adults is proposed to function in avoiding enemies, pair formation, sexual selection and spacing, while in juveniles, vibratory communication is proposed for gallery spacing. However, experimental evidence supporting these functions is lacking. Acoustic sensory organs remain unidentified, and comprehension of signal transmission—whether through airborne sounds or solid‐borne vibrations (or both)—is limited. Bioacoustic technologies have emerged as tools for potential management practices and are also discussed. Based on these findings, we recommend three directions for future research: (1) characterize acoustic morphology and behaviours in more species, particularly unrepresented taxa, with recordings in various contexts, preferably under natural conditions; (2) test hypotheses to explain the functions of acoustic communication through experimental and comparative phylogenetic methods and (3) investigate how sounds or vibrations are transmitted and received through behavioural and neurophysiological experiments. Advancements in bark beetle acoustic sensing and communication research will enhance our understanding of their sensory ecology and facilitate potential control measures of these fascinating insects.
Overcoming (vegan) burnout: Mass gatherings can provide respite and rekindle shared identity and social action efforts in moralized minority groups
Authors: Prosser Annayah M. B. , O'Neill Saffron , Whitmarsh Lorraine , Bolderdijk Jan Willem , Kurz Tim , Blackwood Leda
Published: June 2024

Moralized minority actors can play important roles in social change processes by rejecting majority social norms and modeling alternative societal pathways. However, being a minority actor can be difficult, often resulting in stigma, derogation, and hostility from the majority group. For actions intrinsically linked with daily life (e.g., eating), such social obstacles might become so great that individuals acting alone experience activist burnout' and social isolation, and may stop pursuing social change altogether. Event‐based interventions are a promising (yet currently understudied) avenue for ameliorating these negative consequences and maintaining minority‐driven social change. Through on‐site field interviews (N = 20), we explore how attending an identity‐centering mass gathering (“The Vegan Campout”) acts to validate and empower a minority group (vegans) seeking social change. We show how the event functioned as a space where vegan identity, food, and action were centered and celebrated, in stark contrast to vegans' experiences of a majority meat‐eating society, where they often experienced negativity. Experiencing a 'temporary social majority' context provided important respite for vegans to gain strength, rekindle their vegan identities, and (re)affirm their commitment to activism. Our findings provide insight into the benefits of identity‐centering events for sustaining social change efforts among moralized minority groups.
Persistence in the benefits of foreign ownership: Evidence from divestment
Authors: Ho Chun‐Yu , Sung Ji Hee , Sung Won
Published: June 2024

In this paper, we examine the persistence of benefits from foreign ownership, which informs the proper FDI policies. We exploit the divestment of foreign affiliates in South Korea from 2007 to 2019 as a quasi‐experiment to estimate such persistence of benefits. Our empirical analysis at firm‐level based on the propensity score reweighted difference‐in‐differences model leads to several conclusions. First, on average, the productivity benefit from foreign ownership does not persist after the divestment. Second, the productivity benefit of foreign ownership is persistent in firms with a higher absorptive capacity, measured by R&D intensity, intangible assets, and skilled workers. Such persistence is strengthened if the former foreign affiliate has a longer duration of ownership before the divestment. It suggests that absorptive capacity and time input are helpful for foreign affiliates to persistently absorb knowledge from their owners. Finally, we find that the productivity benefits of foreign ownership are less persistent at former foreign affiliates relying more on external trade.
A short simulated nature experience as an effective way to promote restoration from work‐related stress
Authors: Koivisto Mika , Koskinen Juho , Jokiaho Samu , Vahanne Tero , Pohjola Mikko , Kontio Elina
Published: June 2024

Spending time in nature, and even watching images or videos of nature, has positive effects on one's mental state. However, cognitively stressful work is often performed indoors, in offices that lack easy access to nature during breaks. In this study, we investigated whether watching a 5‐min audiovisual video that describes a first‐person perspective walk on a forest path could help to restore one's mental state after cognitive stress. Participants were asked to perform cognitive stressor tasks, after which they were shown either a nature walk video or a control video. Subjective restoration was measured using self‐reports before and after the videos, while electrodermal activity (EDA) and electroencephalography (EEG) were measured during the video‐watching session. The results showed that experiencing the nature walk video enhanced subjective restoration more than watching the control video. Arousal of the autonomic nervous system, measured using EDA, decreased more during the nature walk video than during the control video. Additionally, activity in the EEG's upper theta band (6–8 Hz) and lower alpha band (8–10 Hz) increased during the nature walk video, suggesting that it induced a relaxed state of mind. Interestingly, the participants' connection with nature moderated the effects of the nature video. The subjective and physiological measures both suggest that watching a short, simulated nature walk may be beneficial in relaxing the mind and restoring one's mental state after cognitive stress.
Functional characterization of polyphenol oxidase OfPPO2 supports its involvement in parallel biosynthetic pathways of acteoside
Authors: Liu Yating , Han Xiaoyang , Zhao Mengya , Liu Lan , Deng Zixin , Zhao Qiu , Yu Yi
Published: June 2024

Acteoside is a bioactive phenylethanoid glycoside widely distributed throughout the plant kingdom. Because of its two catechol moieties, acteoside displays a variety of beneficial activities. The biosynthetic pathway of acteoside has been largely elucidated, but the assembly logic of two catechol moieties in acteoside remains unclear. Here, we identified a novel polyphenol oxidase OfPPO2 from Osmanthus fragrans, which could hydroxylate various monophenolic substrates, including tyrosine, tyrosol, tyramine, 4‐hydroxyphenylacetaldehyde, salidroside, and osmanthuside A, leading to the formation of corresponding catechol‐containing intermediates for acteoside biosynthesis. OfPPO2 could also convert osmanthuside B into acteoside, creating catechol moieties directly via post‐modification of the acteoside skeleton. The reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) analysis and subcellular localization assay further support the involvement of OfPPO2 in acteoside biosynthesis in planta. These findings suggest that the biosynthesis of acteoside in O. fragrans may follow “parallel routes” rather than the conventionally considered linear route. In support of this hypothesis, the glycosyltransferase OfUGT and the acyltransferase OfAT could direct the flux of diphenolic intermediates generated by OfPPO2 into acteoside. Significantly, OfPPO2 and its orthologs constitute a functionally conserved enzyme family that evolved independently from other known biosynthetic enzymes of acteoside, implying that the substrate promiscuity of this PPO family may offer acteoside‐producing plants alternative ways to synthesize acteoside. Overall, this work expands our understanding of parallel pathways plants may employ to efficiently synthesize acteoside, a strategy that may contribute to plants' adaptation to environmental challenges.
In‐depth exploration of the genomic diversity in tea varieties based on a newly constructed pangenome of Camellia sinensis
Authors: Tariq Arslan , Meng Minghui , Jiang Xiaohui , Bolger Anthony , Beier Sebastian , Buchmann Jan P. , Fernie Alisdair R. , Wen Weiwei , Usadel Björn
Published: June 2024

Tea, one of the most widely consumed beverages globally, exhibits remarkable genomic diversity in its underlying flavour and health‐related compounds. In this study, we present the construction and analysis of a tea pangenome comprising a total of 11 genomes, with a focus on three newly sequenced genomes comprising the purple‐leaved assamica cultivar “Zijuan”, the temperature‐sensitive sinensis cultivar “Anjibaicha” and the wild accession “L618” whose assemblies exhibited excellent quality scores as they profited from latest sequencing technologies. Our analysis incorporates a detailed investigation of transposon complement across the tea pangenome, revealing shared patterns of transposon distribution among the studied genomes and improved transposon resolution with long read technologies, as shown by long terminal repeat (LTR) Assembly Index analysis. Furthermore, our study encompasses a gene‐centric exploration of the pangenome, exploring the genomic landscape of the catechin pathway with our study, providing insights on copy number alterations and gene‐centric variants, especially for Anthocyanidin synthases. We constructed a gene‐centric pangenome by structurally and functionally annotating all available genomes using an identical pipeline, which both increased gene completeness and allowed for a high functional annotation rate. This improved and consistently annotated gene set will allow for a better comparison between tea genomes. We used this improved pangenome to capture the core and dispensable gene repertoire, elucidating the functional diversity present within the tea species. This pangenome resource might serve as a valuable resource for understanding the fundamental genetic basis of traits such as flavour, stress tolerance, and disease resistance, with implications for tea breeding programmes.
Cell‐free DNA kinetics in response to muscle‐damaging exercise: A drop jump study
Authors: Juškevičiūtė Ema , Neuberger Elmo , Eimantas Nerijus , Heinkel Kirsten , Simon Perikles , Brazaitis Marius
Published: June 2024

A significant increase in circulating cell‐free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle‐damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low‐frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed‐onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low‐frequency fatigue and delayed‐onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P < 0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low‐frequency fatigue (r = −0.52, P = 3.4 × 10−11) and delayed‐onset muscle soreness (r = 0.32, P = 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres.
Rapid Rail Transit (Metro) System. Implementation and Expansion Technical and Operational Challenges Review - The D.C. Metrorail Case Study
Authors: Barbosa Fábio C.
Published: June 2024

The Rapid Rail Transit (Metro) systems have been set as an important tool for world cities to supply the transit riders (users) the mobility and accessibility requirements in the high demand (highly loaded) urban corridors, which require a combination of large passenger capacity and service quality.

Given their large capacity and the associated high service level and environmental performance, the metro systems provide a high quality accessibility, which ultimately, set them as a structural tool to drive the long term urban spatial and economic development.

Metro systems are set as urban megaprojects, given their required very large outlays of capital intensive investments on long-lived assets, such as guideways, stations, rolling stock, and the associated systems (electrification and signaling). The system’s design features might strongly affect its capacity, operational flexibility, service performance, and cost, with the passenger-carrying capacity in the highest-demand sections of the network being one of the most critical design parameters, given its effect on the system’s investments.

This work presents, based on the state of the art available public technical data, a review of the rail metro technology challenges associated with their implementation and expansion initiatives. To do so, it reports the Washington D.C. (District of Columbia) Metrorail experience, at the United States (U.S.), an iconic metro system, which has been successfully planned in the sixties and implemented in the, which has revolutionized the greater Washington Metropolitan Area mobility and urban planning and that currently is set among the busiest metro systems in the U.S.

Nevertheless, despite its groundbreaking transit performance, it currently faces both refurbishment (rehabilitation) and expansion demands, whose diagnosis and proposed solutions are reported in this paper to illustrate the metro rail challenges to provide the required adequate transit service throughout its service life.
An alternative to the igneous crust fluid + sediment melt paradigm for arc lava geochemistry
Authors: Turner Stephen J. , Langmuir Charles H.
Published: June 2024

A long-standing paradigm of arc geochemistry is that the trace element compositions of arc lavas arise from two compositionally distinct slab components: an aqueous dehydration fluid from the subducting igneous ocean crust that transports “fluid-mobile” elements, such as barium (Ba), and a sediment melt that supplies thorium (Th) and the light rare earth elements. This two-component framework has been widely called upon to explain global geochemical trends as well as geochemical variations within individual arcs, such as the Marianas. Here, we show that this paradigm is inconsistent with mass balance, due to the low Ba contents of igneous ocean crust, and with experimental data, which show that aqueous fluids from the igneous oceanic crust would be too dilute to substantially affect arc compositions. Observations previously attributed to the sediment melt/igneous-crust-fluid hypothesis are better explained by diverse subducting sediment compositions coupled with ambient mantle wedge heterogeneity, both globally and for the Marianas.
Retention-aware zero-shifting technique for Tiki-Taka algorithm-based analog deep learning accelerator
Authors: Noh Kyungmi , Kwak Hyunjeong , Son Jeonghoon , Kim Seungkun , Um Minseong , Kang Minil , Kim Doyoon , Ji Wonjae , Lee Junyong , Jo HwiJeong , Woo Jiyong , Lee Hyung-Min , Kim Seyoung
Published: June 2024

We present the fabrication of 4 K-scale electrochemical random-access memory (ECRAM) cross-point arrays for analog neural network training accelerator and an electrical characteristic of an 8 × 8 ECRAM array with a 100% yield, showing excellent switching characteristics, low cycle-to-cycle, and device-to-device variations. Leveraging the advances of the ECRAM array, we showcase its efficacy in neural network training using the Tiki-Taka version 2 algorithm (TTv2) tailored for non-ideal analog memory devices. Through an experimental study using ECRAM devices, we investigate the influence of retention characteristics on the training performance of TTv2, revealing that the relative location of the retention convergence point critically determines the available weight range and, consequently, affects the training accuracy. We propose a retention-aware zero-shifting technique designed to optimize neural network training performance, particularly in scenarios involving cross-point devices with limited retention times. This technique ensures robust and efficient analog neural network training despite the practical constraints posed by analog cross-point devices.
Memory-less scattering imaging with ultrafast convolutional optical neural networks
Authors: Zhang Yuchao , Zhang Qiming , Yu Haoyi , Zhang Yinan , Luan Haitao , Gu Min
Published: June 2024

The optical memory effect in complex scattering media including turbid tissue and speckle layers has been a critical foundation for macroscopic and microscopic imaging methods. However, image reconstruction from strong scattering media without the optical memory effect has not been achieved. Here, we demonstrate image reconstruction through scattering layers where no optical memory effect exists, by developing a multistage convolutional optical neural network (ONN) integrated with multiple parallel kernels operating at the speed of light. Training this Fourier optics-based, parallel, one-step convolutional ONN with the strong scattering process for direct feature extraction, we achieve memory-less image reconstruction with a field of view enlarged by a factor up to 271. This device is dynamically reconfigurable for ultrafast multitask image reconstruction with a computational power of 1.57 peta-operations per second (POPS). Our achievement establishes an ultrafast and high energy-efficient optical machine learning platform for graphic processing.
Icosahedral supracrystal assembly from polymer-grafted nanoparticles via interplay of interfacial energy and confinement effect
Authors: Xu Meng , Kim Eun Ji , Lee Young Jun , Lee Hyunsoo , Jung Kyunghyun , Choi Jaeyoung , Kim Shin-Hyun , Kim YongJoo , Yun Hongseok , Kim Bumjoon J.
Published: June 2024

Self-assembly of nanoparticles (NPs) in drying emulsion droplets paves the way for intricate three-dimensional (3D) superstructures, given the myriad of control parameters for fine-tuning assembly conditions. With their substantial energetic dynamics that are acutely responsive to emulsion confinements, polymeric ligands incorporated into a system can enrich its structural diversity. Here, we demonstrate the assembly of soft polymer-grafted NPs into Mackay icosahedrons beyond spherical body-centered cubic (BCC) packing structures commonly observed for these soft spheres. This behavior is governed by the free energy minimization within emulsions through the interplay of the oil-water interfacial energy and confinement effect as demonstrated by the experimental observations of structural transitions between icosahedrons and BCC crystals and by corresponding free energy calculations. The anisotropic surface of the icosahedral supracrystals provides the capability of guiding the position of a secondary constituent, creating unique hybrid patchy icosahedrons with the potential to develop into multifunctional 3D clusters that combine the benefits of both polymers and conventional colloids.
ComI inhibits transformation in
Bacillus subtilis
by selectively killing competent cells
Authors: Smith Dominique R. , Kearns Daniel B. , Burton Briana M.
Published: June 2024

Many bacteria build elaborate molecular machines to import DNA via natural competence, yet this activity is often not identified until strains have been handled and domesticated in laboratory settings. For example, one of the best studied Gram-positive model organisms,
Bacillus subtilis,
has a poorly transformable ancestor. Transformation in the ancestral strain is inhibited by a transmembrane peptide, ComI, which is encoded on an extrachromosomal plasmid. Although ComI was shown to be necessary and sufficient to inhibit transformation when produced at high levels under an inducible promoter, the mechanism by which ComI inhibits transformation is unknown. Here, we examine the native regulation and mechanism of transformation inhibition by ComI. We find that under native regulation, ComI expression is restricted in the absence of the plasmid. In the presence of the plasmid, we find that ComI is expressed at higher levels in cells that are differentiating into a competent state. The subcellular localization of ComI, however, does not depend on any other competence proteins, and permeabilization activity is concentration-dependent. Time-lapse microscopy reveals that competent cells producing ComI are first permeabilized and then die. Based on these observations, we propose a new model for the mechanism of ComI in which response to competence activation leads to selective elimination of the competent subpopulation.

IMPORTANCE

Natural transformation mechanisms have been studied across several bacterial systems, but few examples of inhibition exist. This work investigates the mechanism of action of a plasmid-encoded transmembrane inhibitor of natural transformation. The data reveal that the peptide can cause cell permeabilization. Permeabilization is synergistic with entry of
Bacillus subtilis
into the “competent” state, such that cells with the ability to be transformed are preferentially killed. These findings reveal a self-preservation mechanism coupled to the physiological state of the cells that ensures that the population can maintain an unaltered plasmid and its predicted prophage.
Unraveling the cryptic functions of mitogen-activated protein kinases Cpk2 and Mpk2 in
Cryptococcus neoformans
Authors: ­Jang Yu-Byeong , Kim Jin-Young , Bahn Yong-Sun
Published: June 2024

Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete
Cryptococcus neoformans
, known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity. However, the roles of Cpk2 and Mpk2 are less understood. Our study elucidates the functional interplay between the Cpk1/Cpk2 and Mpk1/Mpk2 MAPK pathways in
C. neoformans
. We discovered that
CPK2
overexpression compensates for
cpk1
Δ mating deficiencies via the Mat2 transcription factor, revealing functional redundancy between Cpk1 and Cpk2. We also found that Mpk2 is phosphorylated in response to cell wall stress, a process regulated by the MAPK kinase (MAP2K) Mkk2 and MAP2K kinases (MAP3Ks) Ssk2 and Ste11. Overexpression of
MPK2
partially restores cell wall integrity in
mpk1
Δ by influencing key cell wall components, such as chitin and the polysaccharide capsule. Contrarily,
MPK2
overexpression cannot restore thermotolerance and cell membrane integrity in
mpk1
Δ. These results suggest that Mpk1 and Mpk2 have redundant and opposing roles in the cellular response to cell wall and membrane stresses. Most notably, the dual deletion of
MPK1
and
MPK2
restores wild-type mating efficiency in
cpk1
Δ mutants via upregulation of the mating-regulating transcription factors
MAT2
and
ZNF2
, suggesting that the Mpk1 and Mpk2 cooperate to negatively regulate the pheromone-responsive Cpk1 MAPK pathway. Our research collectively underscores a sophisticated regulatory network of cryptococcal MAPK signaling pathways that intricately govern sexual reproduction and cell wall integrity, thereby controlling fungal development and pathogenicity.

IMPORTANCE

In the realm of fungal biology, our study on
Cryptococcus neoformans
offers pivotal insights into the roles of specific proteins called mitogen-activated protein kinases (MAPKs). Here, we discovered the cryptic functions of Cpk2 and Mpk2, two MAPKs previously overshadowed by their dominant counterparts Cpk1 and Mpk1, respectively. Our findings reveal that these “underdog” proteins are not just backup players; they play crucial roles in vital processes like mating and cell wall maintenance in
C. neoformans
. Their ability to step in and compensate when their dominant counterparts are absent showcases the adaptability of
C. neoformans
. This newfound understanding not only enriches our knowledge of fungal MAPK mechanisms but also underscores the intricate balance and interplay of proteins in ensuring the organism’s survival and adaptability.
JCPyV infection of primary choroid plexus epithelial cells reduces expression of critical junctional proteins and increases expression of barrier disrupting inflammatory cytokines
Authors: Haley Sheila A. , O'Hara Bethany A. , Schorl Christoph , Atwood Walter J.
Published: June 2024

The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are immunocompromised due to underlying infections, cancer, or to immunomodulatory treatments for autoimmune disease are at risk for developing progressive multifocal leukoencephalopathy (PML) when the virus invades the CNS and infects macroglial cells in the brain parenchyma. It is not yet known how the virus enters the CNS to cause disease. The blood-choroid plexus barrier is a potential site of virus invasion as the cells that make up this barrier are known to be infected with virus both
in vivo
and
in vitro
. To understand the effects of virus infection on these cells we challenged primary human choroid plexus epithelial cells with JCPyV and profiled changes in host gene expression. We found that viral infection induced the expression of proinflammatory chemokines and downregulated junctional proteins essential for maintaining blood-CSF and blood-brain barrier function. These data contribute to our understanding of how JCPyV infection of the choroid plexus can modulate the host cell response to neuroinvasive pathogens.

IMPORTANCE

The human polyomavirus, JCPyV, causes a rapidly progressing demyelinating disease in the CNS of patients whose immune systems are compromised. JCPyV infection has been demonstrated in the choroid plexus both
in vivo
and
in vitro
and this highly vascularized organ may be important in viral invasion of brain parenchyma. Our data show that infection of primary choroid plexus epithelial cells results in increased expression of pro-inflammatory chemokines and downregulation of critical junctional proteins that maintain the blood-CSF barrier. These data have direct implications for mechanisms used by JCPyV to invade the CNS and cause neurological disease.
Single nucleotide variation catalog from clinical isolates mapped on tertiary and quaternary structures of ESX-1-related proteins reveals critical regions as putative Mtb therapeutic targets
Authors: Tzfadia Oren , Gijsbers Abril , Vujkovic Alexandra , Snobre Jihad , Vargas Roger , Dewaele Klaas , Meehan Conor J. , Farhat Maha , Hakke Sneha , Peters Peter J. , de Jong Bouke C. , Siroy Axel , Ravelli Raimond B. G.
Published: June 2024

Proteins encoded by the ESX-1 genes of interest are essential for full virulence in all
Mycobacterium tuberculosis
complex (Mtbc) lineages, the pathogens causing the highest mortality worldwide. Identifying critical regions in these ESX-1-related proteins could provide preventive or therapeutic targets for Mtb infection, the game changer needed for tuberculosis control. We analyzed a compendium of whole genome sequences of clinical Mtb isolates from all lineages from >32,000 patients and identified single nucleotide polymorphisms. When mutations corresponding to all non-synonymous single nucleotide polymorphisms were mapped on structural models of the ESX-1 proteins, fully conserved regions emerged. Some could be assigned to known quaternary structures, whereas others could be predicted to be involved in yet-to-be-discovered interactions. Some mutants had clonally expanded (found in >1% of the isolates); these mutants were mostly located at the surface of globular domains, remote from known intra- and inter-molecular protein–protein interactions. Fully conserved intrinsically disordered regions of proteins were found, suggesting that these regions are crucial for the pathogenicity of the Mtbc. Altogether, our findings highlight fully conserved regions of proteins as attractive vaccine antigens and drug targets to control Mtb virulence. Extending this approach to the whole Mtb genome as well as other microorganisms will enhance vaccine development for various pathogens.

IMPORTANCE

We mapped all non-synonymous single nucleotide polymorphisms onto each of the experimental and predicted ESX-1 proteins’ structural models and inspected their placement. Varying sizes of conserved regions were found. Next, we analyzed predicted intrinsically disordered regions within our set of proteins, finding two putative long stretches that are fully conserved, and discussed their potential essential role in immunological recognition. Combined, our findings highlight new targets for interfering with
Mycobacterium tuberculosis
complex virulence.
Neonatal adrenal haemorrhage with contralateral scrotal haematoma and inguinal ecchymosis
Authors: Ng Benjamin Wei-Liang , Lim Vichard , Aizulkamal Aiza Hazima , Ramanaidu Vengkatarao
Published: June 2024

Neonatal adrenal haemorrhage (NAH) is more frequently described in neonates due to their relatively larger size and increased vascularity. While most are asymptomatic, they can present with anaemia, jaundice, abdominal mass, scrotal haematoma or more severe complications such as shock and adrenal insufficiency. Scrotal haematoma seen with NAH may be mistaken for other more serious conditions causing acute scrotum. Prompt sonographic examination that includes the bilateral adrenal glands may help to detect NAH early and to avoid unnecessary interventions. Cases of NAH causing ipsilateral inguinal ecchymosis and scrotal haematoma have been reported, but contralateral haematomas are very rare. In this report, we present a unique case of a neonate with an antenatally acquired adrenal haematoma complicated with an acute peripartum rebleeding manifesting as a contralateral scrotal haematoma and inguinal ecchymosis. The NAH was treated conservatively and resolved on follow-up imaging.
Population-level impact of the BMJ Rapid Recommendation for colorectal cancer screening: a microsimulation analysis
Authors: van Duuren Luuk A , Bulliard Jean-Luc , Mohr Ella , van den Puttelaar Rosita , Plys Ekaterina , Brändle Karen , Corley Douglas A , Froehlich Florian , Selby Kevin , Lansdorp-Vogelaar Iris
Published: June 2024

Objective

In 2019, a BMJ Rapid Recommendation advised against colorectal cancer (CRC) screening for adults with a predicted 15-year CRC risk below 3%. Using Switzerland as a case study, we estimated the population-level impact of this recommendation.

Design

We predicted the CRC risk of all respondents to the population-based Swiss Health Survey. We derived the distribution of risk-based screening start age, assuming predicted risk was calculated every 5 years between ages 25 and 70 and screening started when this risk exceeded 3%. Next, the MISCAN-Colon microsimulation model evaluated biennial faecal immunochemical test (FIT) screening with this risk-based start age. As a comparison, we simulated screening initiation based on age and sex.

Results

Starting screening only when predicted risk exceeded 3% meant 82% of women and 90% of men would not start screening before age 65 and 60, respectively. This would require 43%–57% fewer tests, result in 8%–16% fewer CRC deaths prevented and yield 19%–33% fewer lifeyears gained compared with screening from age 50. Screening women from age 65 and men from age 60 had a similar impact as screening only when predicted risk exceeded 3%.

Conclusion

With the recommended risk prediction tool, the population impact of the BMJ Rapid Recommendation would be similar to screening initiation based on age and sex only. It would delay screening initiation by 10–15 years. Although halving the screening burdens, screening benefits would be reduced substantially compared with screening initiation at age 50. This suggests that the 3% risk threshold to start CRC screening might be too high.
Taipei Medical University Clinical Research Database: a collaborative hospital EHR database aligned with international common data standards
Authors: Nguyen Phung-Anh , Hsu Min-Huei , Chang Tzu-Hao , Yang Hsuan-Chia , Huang Chih-Wei , Liao Chia-Te , Lu Christine Y. , Hsu Jason C.
Published: June 2024

Objective

The objective of this paper is to provide a comprehensive overview of the development and features of the Taipei Medical University Clinical Research Database (TMUCRD), a repository of real-world data (RWD) derived from electronic health records (EHRs) and other sources.

Methods

TMUCRD was developed by integrating EHRs from three affiliated hospitals, including Taipei Medical University Hospital, Wan-Fang Hospital and Shuang-Ho Hospital. The data cover over 15 years and include diverse patient care information. The database was converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) for standardisation.

Results

TMUCRD comprises 89 tables (eg, 29 tables for each hospital and 2 linked tables), including demographics, diagnoses, medications, procedures and measurements, among others. It encompasses data from more than 4.15 million patients with various medical records, spanning from the year 2004 to 2021. The dataset offers insights into disease prevalence, medication usage, laboratory tests and patient characteristics.

Discussion

TMUCRD stands out due to its unique advantages, including diverse data types, comprehensive patient information, linked mortality and cancer registry data, regular updates and a swift application process. Its compatibility with the OMOP CDM enhances its usability and interoperability.

Conclusion

TMUCRD serves as a valuable resource for researchers and scholars interested in leveraging RWD for clinical research. Its availability and integration of diverse healthcare data contribute to a collaborative and data-driven approach to advancing medical knowledge and practice.
Risk prediction of advanced colorectal neoplasia varies by race and neighbourhood socioeconomic status
Authors: Sun Xiangqing , Chen Zhengyi , Cooper Gregory S , Berger Nathan A , Coulton Claudia , Li Li
Published: June 2024

Objective

Neighbourhood deprivation increases the risk of colorectal neoplasia and contributes to racial disparities observed in this disease. Developing race-specific advanced colorectal neoplasia (ACN) prediction models that include neighbourhood socioeconomic status has the potential to improve the accuracy of prediction.

Methods

The study includes 1457 European Americans (EAs) and 936 African Americans (AAs) aged 50–80 years undergoing screening colonoscopy. Race-specific ACN risk prediction models were developed for EAs and AAs, respectively. Area Deprivation Index (ADI), derived from 17 variables of neighbourhood socioeconomic status, was evaluated by adding it to the ACN risk prediction models. Prediction accuracy was evaluated by concordance statistic (C-statistic) for discrimination and Hosmer-Lemeshow goodness-of-fit test for calibration.

Results

With fewer predictors, the EA-specific and AA-specific prediction models had better prediction accuracy in the corresponding race/ethnic subpopulation than the overall model. Compared with the overall model which had poor calibration (PCalibration=0.053 in the whole population andPCalibration=0.011 in AAs), the EA model had C-statistic of 0.655 (95% CI 0.594 to 0.717) andPCalibration=0.663; and the AA model had C-statistic of 0.637 ((95% CI 0.572 to 0.702) andPCalibration=0.810. ADI was a significant predictor of ACN in EAs (OR=1.24 ((95% CI 1.03 to 1.50),P=0.029), but not in AAs (OR=1.07 ((95% CI 0.89 to 1.28),P=0.487). Adding ADI to the EA-specific ACN prediction model substantially improved ACN calibration accuracy of the prediction across area deprivation groups (PCalibration=0.924 with ADI vsPCalibration=0.140 without ADI) in EAs.

Conclusions

Neighbourhood socioeconomic status is an important factor to consider in ACN risk prediction modeling. Moreover, non-race-specific prediction models have poor generalisability. Race-specific prediction models incorporating neighbourhood socioeconomic factors are needed to improve ACN prediction accuracy.
Clinical consequences of computer-aided colorectal polyp detection
Authors: Sinonquel Pieter , Eelbode Tom , Pech Oliver , De Wulf Dominiek , Dewint Pieter , Neumann Helmut , Antonelli Giulio , Iacopini Federico , Tate David , Lemmers Arnaud , Pilonis Nastazja Dagny , Kaminski Michal Filip , Roelandt Philip , Hassan Cesare , Ingrid Demedts , Maes Frederik , Bisschops Raf
Published: June 2024

Background and aim

Randomised trials show improved polyp detection with computer-aided detection (CADe), mostly of small lesions. However, operator and selection bias may affect CADe’s true benefit. Clinical outcomes of increased detection have not yet been fully elucidated.

Methods

In this multicentre trial, CADe combining convolutional and recurrent neural networks was used for polyp detection. Blinded endoscopists were monitored in real time by a second observer with CADe access. CADe detections prompted reinspection. Adenoma detection rates (ADR) and polyp detection rates were measured prestudy and poststudy. Histological assessments were done by independent histopathologists. The primary outcome compared polyp detection between endoscopists and CADe.

Results

In 946 patients (51.9% male, mean age 64), a total of 2141 polyps were identified, including 989 adenomas. CADe was not superior to human polyp detection (sensitivity 94.6% vs 96.0%) but outperformed them when restricted to adenomas. Unblinding led to an additional yield of 86 true positive polyp detections (1.1% ADR increase per patient; 73.8% were <5 mm). CADe also increased non-neoplastic polyp detection by an absolute value of 4.9% of the cases (1.8% increase of entire polyp load). Procedure time increased with 6.6±6.5 min (+42.6%). In 22/946 patients, the additional detection of adenomas changed surveillance intervals (2.3%), mostly by increasing the number of small adenomas beyond the cut-off.

Conclusion

Even if CADe appears to be slightly more sensitive than human endoscopists, the additional gain in ADR was minimal and follow-up intervals rarely changed. Additional inspection of non-neoplastic lesions was increased, adding to the inspection and/or polypectomy workload.