bluuebunny/crossref_metadata_2025 huggingface dataset:
SITI Training: Viewpoints and the Suzuki Method for Cross-Cultural Collaboration
Authors: Montanini Lorenzo
Published: February 2024

The training that the Saratoga International Theater Institute (SITI) perfected during its thirty years of existence is its most relevant heritage. SITI believed that training was a crucial part of a performer’s education and ethos. Its constitutive elements – Viewpoints and the Suzuki Method for actor training – are here put in a dialectical opposition that nurtures hybridization. This article investigates how, in fact, these two trainings intersect and also form new ‘languages’ (that is, systems of representation) whenever they are performed. A contextual analysis of SITI’s training as a foundation for making work and as a means for educating actors provides a clearer understanding of why and how SITI training is an instrument that facilitates and fosters cross-cultural collaboration.
From treaty to custom: Shifting paths in the recent development of international humanitarian law
Authors: Mantilla Giovanni
Published: February 2024

From 1864 to the 1970s, international humanitarian law (IHL) changed through the path of formal treaty revision. Since 1977, however, purported changes to IHL have come not from treaty making but from interpretation, particularly through claims about the attainment of customary status by existing treaty rules. This article explains this shift as the result of the attitudes and choices of key IHL stakeholders under the changed conditions of post-Second World War multilateralism. It argues that the turn toward customary law claims-making was a reaction to the negotiation politics and contested outcomes of the 1977 Additional Protocols (APs) to the Geneva Conventions. After 1977, leading actors looked to custom as a means of arresting or encouraging legal change. The resulting, much-expanded IHL has proved influential and authoritative, even if its precise degree of acceptance by states remains unclear.
Are prosocial tendencies relevant for developmental psychopathology? The relations of prosocial behavior and empathy-related responding to externalizing problems, internalizing problems, and autism spectrum disorder
Authors: Eisenberg Nancy , Zuffianò Antonio , Spinrad Tracy L.
Published: February 2024

The field of developmental psychopathology tends to focus on the negative aspects of functioning. However, prosocial behavior and empathy-related responding – positive aspects of functioning– might relate to some aspects of psychopathology in meaningful ways. In this article, we review research on the relations of three types of developmental psychopathology– externalizing problems (EPs), internalizing problems (IPs), and Autism Spectrum Disorder (ASD) – to empathy-related responding (e.g., affective and cognitive empathy, sympathy, personal distress) and prosocial behavior. Empathy-related responding and prosocial behavior generally have been inversely related to EPs, although findings are sometimes reversed for young children and, for empathy, weak for reactive aggression. Some research indicates that children’s empathy (often measured as emotional contagion) and personal distress are positively related to IPs, suggesting that strong sensitivity to others’ emotions is harmful to some children. In contrast, prosocial behaviors are more consistently negatively related to IPs, although findings likely vary depending on the motivation for prosocial behavior and the recipient. Children with ASD are capable of prosocially and empathy-related responding, although parents report somewhat lower levels of these characteristics for ASD children compared to neurotypical peers. Issues in regard to measurement, motivation for prosociality, causal relations, and moderating and mediating factors are discussed.
Developmental psychopathology: Our welcoming, inclusive, and eclectic intellectual home
Authors: Kochanska Grazyna , An Danming
Published: February 2024

The integrative nature of developmental psychopathology is its defining and most remarkable feature. Since its inception, often identified with the special issue of Child Development (Cichetti, 1984), this new discipline has shattered barriers and divisions that until then had artificially compartmentalized the study of human development, and perhaps even psychology in general, and it has proposed new ways of integrative thinking about development. One, developmental psychopathology has programmatically integrated research on typical or adaptive and atypical or maladaptive developmental processes and demonstrated how those inform each other. Two, developmental psychopathology has promoted bridges between developmental research and other disciplines. Three, less explicitly but equally importantly, developmental psychopathology has abolished conceptual and empirical barriers that had existed among various theories and perspectives within developmental psychology by creating a welcoming niche for research inspired by theories often historically seen as contradictory or incompatible. Ideas originating in psychoanalytic, learning, cognitive, ethological, and sociocultural theories all find a welcoming home and seamlessly coexist in heuristically productive harmony within developmental psychopathology, inform each other, and generate exciting questions and insights. This eclectic and conceptually inclusive nature is one reason for developmental psychopathology’s lasting appeal and inspirational power.
Evaluating the acceptability of remote cognitive remediation from the perspective of psychosis service users
Authors: Parri Lois Ann , Barret Katherine , Hill Rosie , Hoque Arif , Isok Iris , Kenny Alex , Markham Sarah , Oyeleye Nike , Quinn Roisin , Sweeney Angela , Wykes Til , Cella Matteo
Published: February 2024

Objectives:

Cognitive remediation (CR) can reduce the cognitive difficulties experienced by people with psychosis. Adapting CR to be delivered remotely provides new opportunities for extending its use. However, doing so requires further evaluation of its acceptability from service users’ views. We evaluate the acceptability of therapist-supported remote CR from the perspectives of service users using participatory service user-centred methods.

Method:

After receiving 12 weeks of therapist-supported remote CR, service users were interviewed by a service user researcher following a semi-structured 18-question interview guide. Transcripts were analysed using reflexive thematic analysis with themes and codes further validated by a Lived Experience Advisory Panel and member checking.

Results:

The study recruited 26 participants, almost all of whom reported high acceptability of remote CR, and some suggested improvements. Four themes emerged: (1) perceived treatment benefits, (2) remote versus in-person therapy, (3) the therapist’s role, and (4) how it could be better.

Conclusions:

This study used comprehensive service user involvement methods. For some participants, technology use remained a challenge and addressing these difficulties detracted from the therapy experience. These outcomes align with existing research on remote therapy, suggesting that remote CR can expand choice and improve access to treatment for psychosis service users once barriers are addressed. Future use of remote CR should consider technology training and equipment provision to facilitate therapy for service users and therapists.
Wideband filtering power amplifier based on terminated coupled line structure
Authors: Liu Guohua , Yu Jianyuan , Lin Yijun
Published: February 2024

This paper proposes a design method for designing a wideband filtering power amplifier (PA) based on terminated coupled line structure (TCLS). This method generates four transmission zeros and three transmission poles by loading stepped impedance resonator and short-circuit stubs on the four ports of TCLS, which greatly optimizes the in-band return loss and stopband suppression of the output matching network. In addition, the effective suppression of the second harmonic also increases the efficiency of the PA. In order to verify the effectiveness and superiority of this design method, a wideband bandpass filtering PA is designed and manufactured in 2.9–3.7 GHz. Measurement results show that the saturated output power is from 40.1 dBm to 41.2 dBm, the drain efficiency is greater than 60.3%, and the gain is 10–11.2 dB.
A Century of Reforestation Reduced Anthropogenic Warming in the Eastern United States
Authors: Barnes Mallory L. , Zhang Quan , Robeson Scott M. , Young Lily , Burakowski Elizabeth A. , Oishi A. Christopher. , Stoy Paul C. , Katul Gaby , Novick Kimberly A.
Published: February 2024

Restoring and preserving the world's forests are promising natural pathways to mitigate some aspects of climate change. In addition to regulating atmospheric carbon dioxide concentrations, forests modify surface and near‐surface air temperatures through biophysical processes. In the eastern United States (EUS), widespread reforestation during the 20th century coincided with an anomalous lack of warming, raising questions about reforestation's contribution to local cooling and climate mitigation. Using new cross‐scale approaches and multiple independent sources of data, we uncovered links between reforestation and the response of both surface and air temperature in the EUS. Ground‐ and satellite‐based observations showed that EUS forests cool the land surface by 1–2°C annually compared to nearby grasslands and croplands, with the strongest cooling effect during midday in the growing season, when cooling is 2–5°C. Young forests (20–40 years) have the strongest cooling effect on surface temperature. Surface cooling extends to the near‐surface air, with forests reducing midday air temperature by up to 1°C compared to nearby non‐forests. Analyses of historical land cover and air temperature trends showed that the cooling benefits of reforestation extend across the landscape. Locations surrounded by reforestation were up to 1°C cooler than neighboring locations that did not undergo land cover change, and areas dominated by regrowing forests were associated with cooling temperature trends in much of the EUS. Our work indicates reforestation contributed to the historically slow pace of warming in the EUS, underscoring reforestation's potential as a local climate adaptation strategy in temperate regions.
Grass Evolutionary Lineages Can Be Identified Using Hyperspectral Leaf Reflectance
Authors: Slapikas Ryan , Pau Stephanie , Donnelly Ryan C. , Ho Che‐Ling , Nippert Jesse B. , Helliker Brent R. , Riley William J. , Still Christopher J. , Griffith Daniel M.
Published: February 2024

Hyperspectral remote sensing has the potential to map numerous attributes of the Earth’s surface, including spatial patterns of biological diversity. Grasslands are one of the largest biomes on Earth. Accurate mapping of grassland biodiversity relies on spectral discrimination of endmembers of species or plant functional types. We focused on spectral separation of grass lineages that dominate global grassy biomes: Andropogoneae (C4), Chloridoideae (C4), and Pooideae (C3). We examined leaf reflectance spectra (350–2,500 nm) from 43 grass species representing these grass lineages from four representative grassland sites in the Great Plains region of North America. We assessed the utility of leaf reflectance data for classification of grass species into three major lineages and by collection site. Classifications had very high accuracy (94%) that were robust to site differences in species and environment. We also show an information loss using multispectral sensors, that is, classification accuracy of grass lineages using spectral bands provided by current multispectral satellites is much lower (accuracy of 85.2% and 61.3% using Sentinel 2 and Landsat 8 bands, respectively). Our results suggest that hyperspectral data have an exciting potential for mapping grass functional types as informed by phylogeny. Leaf‐level hyperspectral separability of grass lineages is consistent with the potential increase in biodiversity and functional information content from the next generation of satellite‐based spectrometers.
Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy
Authors: Qiao Ya-Nan , Li Lei , Hu Song-Hua , Yang Yuan-Xin , Ma Zhen-Zhen , Huang Lin , An Yan-Peng , Yuan Yi-Yuan , Lin Yan , Xu Wei , Li Yao , Lin Peng-Cheng , Cao Jing , Zhao Jian-Yuan , Zhao Shi-Min
Published: February 2024

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.
Identification of the DNA methylation signature of Mowat-Wilson syndrome
Authors: Caraffi Stefano Giuseppe , van der Laan Liselot , Rooney Kathleen , Trajkova Slavica , Zuntini Roberta , Relator Raissa , Haghshenas Sadegheh , Levy Michael A. , Baldo Chiara , Mandrile Giorgia , Lauzon Carolyn , Cordelli Duccio Maria , Ivanovski Ivan , Fetta Anna , Sukarova Elena , Brusco Alfredo , Pavinato Lisa , Pullano Verdiana , Zollino Marcella , McConkey Haley , Tartaglia Marco , Ferrero Giovanni Battista , Sadikovic Bekim , Garavelli Livia
Published: February 2024

Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the ZEB2 locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis.
Ambient ultraviolet radiation and ocular melanoma incidence in the United States, 2000−2019
Authors: Arockiaraj Basilica M. , Cahoon Elizabeth K. , Sargen Michael R. , Long Erping , Tucker Margaret A. , Mai Jim Z.
Published: February 2024

Background/Objectives

Ocular melanoma is a rare, but deadly cancer. This large cancer registry study examines the associations between solar ultraviolet radiation (UVR) and incidence of different anatomical sites of ocular melanoma by sex, age, laterality, and race and ethnicity.

Methods

Incidence data were derived from 21 cancer registries in the US for the years 2000–2019. Satellite-based UVR estimates were linked to county of residence at diagnosis. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quartiles using Poisson models.

Results

UVR was not associated with total ocular melanoma (N = 18,089) comparing Q4 versus Q1 (IRR = 0.98; 95%CI:0.94,1.03; p-trend = 0.07) or conjunctival melanoma (IRR = 0.99; 95%CI:0.82,1.19; p-trend = 0.81). However, in analyses of continuous UVR (per 10 mW/m2), risks were reduced for total ocular melanoma (IRR = 0.97; 95% CI: 0.96, 0.99). Incidence was increased for ciliary body/iris melanoma in the highest UVR quartile (IRR = 1.63; 95%CI:1.43,1.87; p-trend < 0.0001) and remained increased in non-Hispanic White individuals only. Incidence was reduced for choroidal melanoma in the highest UVR quartile (IRR = 0.86; 95%CI:0.82,0.91; p-trend < 0.0001).

Conclusions

UVR may be associated with increased risk of ciliary body/iris melanoma. Reduced risk of choroidal melanoma may be due to higher diffuse UVR exposure to posterior ocular sites in locations at higher latitudes. Our results support and expand previous findings of associations of UVR using various surrogates on ocular melanoma risk and serve as a starting point for understanding the differences in the relationship between UVR and specific anatomical sites.
Chromosome-level genome assembly of the Japanese sawyer beetle Monochamus alternatus
Authors: Gao Yong-Fu , Yang Fang-Yuan , Song Wei , Cao Li-Jun , Chen Jin-Cui , Shen Xiu-Jing , Qu Liang-Jian , Zong Shi-Xiang , Wei Shu-Jun
Published: February 2024

The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors.
Chromosomal level genome assemblies of two Malus crabapple cultivars Flame and Royalty
Authors: Li Hua , Zhai Xuyang , Peng Haixu , Qing You , Deng Yulin , Zhou Shijie , Bei Tairui , Tian Ji , Zhang Jie , Hu Yujing , Qin Xiaoxiao , Lu Yanfen , Yao Yuncong , Wang Sen , Zheng Yi
Published: February 2024

Malus hybrid ‘Flame’ and Malus hybrid ‘Royalty’ are representative ornamental crabapples, rich in flavonoids and serving as the preferred materials for studying the coloration mechanism. We generated two sets of high-quality chromosome-level and haplotype-resolved genome of ‘Flame’ with sizes of 688.2 Mb and 675.7 Mb, and those of ‘Royalty’ with sizes of 674.1 Mb and 663.6 Mb, all anchored to 17 chromosomes and with a high BUSCO completeness score nearly 99.0%. A total of 47,833 and 47,307 protein-coding genes were annotated in the two haplotype genomes of ‘Flame’, and the numbers of ‘Royalty’ were 46,305 and 46,920 individually. The assembled high-quality genomes offer new resources for studying the origin and adaptive evolution of crabapples and the molecular basis of the accumulation of flavonoids and anthocyanins, facilitating molecular breeding of Malus plants.
Validation of Wistar-Kyoto rats kept in solitary housing as an animal model for depression using voxel-based morphometry
Authors: Yoshii Takanobu , Oishi Naoya , Sotozono Yasutaka , Watanabe Anri , Sakai Yuki , Yamada Shunji , Matsuda Ken-Ichi , Kido Masamitsu , Ikoma Kazuya , Tanaka Masaki , Narumoto Jin
Published: February 2024

Major depressive disorder is a common psychiatric condition often resistant to medication. The Wistar-Kyoto (WKY) rat has been suggested as an animal model of depression; however, it is still challenging to translate results from animal models into humans. Solitary housing is a mild stress paradigm that can simulate the environment of depressive patients with limited social activity due to symptoms. We used voxel-based morphometry to associate the solitary-housed WKY (sWKY) rat model with data from previous human studies and validated our results with behavioural studies. As a result, atrophy in sWKY rats was detected in the ventral hippocampus, caudate putamen, lateral septum, cerebellar vermis, and cerebellar nuclei (p < 0.05, corrected for family-wise error rate). Locomotor behaviour was negatively correlated with habenula volume and positively correlated with atrophy of the cerebellar vermis. In addition, sWKY rats showed depletion of sucrose consumption not after reward habituation but without reward habituation. Although the application of sWKY rats in a study of anhedonia might be limited, we observed some similarities between the regions of brain atrophy in sWKY rats and humans with depression, supporting the translation of sWKY rat studies to humans.
Investigation into scalable and efficient enterotoxigenic Escherichia coli bacteriophage production
Authors: Wiebe Katie G. , Cook Bradley W. M. , Lightly Tasia J. , Court Deborah A. , Theriault Steven S.
Published: February 2024

As the demand for bacteriophage (phage) therapy increases due to antibiotic resistance in microbial pathogens, strategies and methods for increased efficiency, large-scale phage production need to be determined. To date, very little has been published on how to establish scalable production for phages, while achieving and maintaining a high titer in an economical manner. The present work outlines a phage production strategy using an enterotoxigenic Escherichia coli-targeting phage, ‘Phage75’, and accounts for the following variables: infection load, multiplicity of infection, temperature, media composition, harvest time, and host bacteria. To streamline this process, variables impacting phage propagation were screened through a high-throughput assay monitoring optical density at 600 nm (OD600) to indirectly infer phage production from host cell lysis. Following screening, propagation conditions were translated in a scalable fashion in shake flasks at 0.01 L, 0.1 L, and 1 L. A final, proof-of-concept production was then carried out in a CellMaker bioreactor to represent practical application at an industrial level. Phage titers were obtained in the range of 9.5–10.1 log10 PFU/mL with no significant difference between yields from shake flasks and CellMaker. Overall, this suggests that the methodology for scalable processing is reliable for translating into large-scale phage production.
Automatic enhancement preprocessing for segmentation of low quality cell images
Authors: Kato Sota , Hotta Kazuhiro
Published: February 2024

We present a novel automatic preprocessing and ensemble learning technique for the segmentation of low-quality cell images. Capturing cells subjected to intense light is challenging due to their vulnerability to light-induced cell death. Consequently, microscopic cell images tend to be of low quality and it causes low accuracy for semantic segmentation. This problem can not be satisfactorily solved by classical image preprocessing methods. Therefore, we propose a novel approach of automatic enhancement preprocessing (AEP), which translates an input image into images that are easy to recognize by deep learning. AEP is composed of two deep neural networks, and the penultimate feature maps of the first network are employed as filters to translate an input image with low quality into images that are easily classified by deep learning. Additionally, we propose an automatic weighted ensemble learning (AWEL), which combines the multiple segmentation results. Since the second network predicts segmentation results corresponding to each translated input image, multiple segmentation results can be aggregated by automatically determining suitable weights. Experiments on two types of cell image segmentation confirmed that AEP can translate low-quality cell images into images that are easy to segment and that segmentation accuracy improves using AWEL.
Systematic identification of the role of gut microbiota in mental disorders: a TwinsUK cohort study
Authors: Delanote Julie , Correa Rojo Alejandro , Wells Philippa M. , Steves Claire J. , Ertaylan Gökhan
Published: February 2024

Mental disorders are complex disorders influenced by multiple genetic, environmental, and biological factors. Specific microbiota imbalances seem to affect mental health status. However, the mechanisms by which microbiota disturbances impact the presence of depression, stress, anxiety, and eating disorders remain poorly understood. Currently, there are no robust biomarkers identified. We proposed a novel pyramid-layer design to accurately identify microbial/metabolomic signatures underlying mental disorders in the TwinsUK registry. Monozygotic and dizygotic twins discordant for mental disorders were screened, in a pairwise manner, for differentially abundant bacterial genera and circulating metabolites. In addition, multivariate analyses were performed, accounting for individual-level confounders. Our pyramid-layer study design allowed us to overcome the limitations of cross-sectional study designs with significant confounder effects and resulted in an association of the abundance of genus Parabacteroides with the diagnosis of mental disorders. Future research should explore the potential role of Parabacteroides as a mediator of mental health status. Our results indicate the potential role of the microbiome as a modifier in mental disorders that might contribute to the development of novel methodologies to assess personal risk and intervention strategies.
FMO-guided design of darunavir analogs as HIV-1 protease inhibitors
Authors: Chuntakaruk Hathaichanok , Hengphasatporn Kowit , Shigeta Yasuteru , Aonbangkhen Chanat , Lee Vannajan Sanghiran , Khotavivattana Tanatorn , Rungrotmongkol Thanyada , Hannongbua Supot
Published: February 2024

The prevalence of HIV-1 infection continues to pose a significant global public health issue, highlighting the need for antiretroviral drugs that target viral proteins to reduce viral replication. One such target is HIV-1 protease (PR), responsible for cleaving viral polyproteins, leading to the maturation of viral proteins. While darunavir (DRV) is a potent HIV-1 PR inhibitor, drug resistance can arise due to mutations in HIV-1 PR. To address this issue, we developed a novel approach using the fragment molecular orbital (FMO) method and structure-based drug design to create DRV analogs. Using combinatorial programming, we generated novel analogs freely accessible via an on-the-cloud mode implemented in Google Colab, Combined Analog generator Tool (CAT). The designed analogs underwent cascade screening through molecular docking with HIV-1 PR wild-type and major mutations at the active site. Molecular dynamics (MD) simulations confirmed the assess ligand binding and susceptibility of screened designed analogs. Our findings indicate that the three designed analogs guided by FMO, 19–0–14–3, 19–8–10–0, and 19–8–14–3, are superior to DRV and have the potential to serve as efficient PR inhibitors. These findings demonstrate the effectiveness of our approach and its potential to be used in further studies for developing new antiretroviral drugs.
Validation of computational fluid dynamics of shake flask experiments at moderate viscosity by liquid distributions and volumetric power inputs
Authors: Dinter Carl , Gumprecht Andreas , Menze Matthias Alexander , Azizan Amizon , Niehoff Paul-Joachim , Hansen Sven , Büchs Jochen
Published: February 2024

Computational fluid dynamics (CFD) has recently become a pivotal tool in the design and scale-up of bioprocesses. While CFD has been extensively utilized for stirred tank reactors (STRs), there exists a relatively limited body of literature focusing on CFD applications for shake flasks, almost exclusively concentrated on fluids at waterlike viscosity. The importance of CFD model validation cannot be overstated. While techniques to elucidate the internal flow field are necessary for model validation in STRs, the liquid distribution, caused by the orbital shaking motion of shake flasks, can be exploited for model validation. An OpenFOAM CFD model for shake flasks has been established. Calculated liquid distributions were compared to suitable, previously published experimental data. Across a broad range of shaking conditions, at waterlike and moderate viscosity (16.7 mPa∙s), the CFD model's liquid distributions align excellently with the experimental data, in terms of overall shape and position of the liquid relative to the direction of the centrifugal force. Additionally, the CFD model was used to calculate the volumetric power input, based on the energy dissipation. Depending on the shaking conditions, the computed volumetric power inputs range from 0.1 to 7 kW/m3 and differed on average by 0.01 kW/m3 from measured literature data.
Technical optimization of spatially resolved single-cell transcriptomic datasets to study clinical liver disease
Authors: Rocque Brittany , Guion Kate , Singh Pranay , Bangerth Sarah , Pickard Lauren , Bhattacharjee Jashdeep , Eguizabal Sofia , Weaver Carly , Chopra Shefali , Zhou Shengmei , Kohli Rohit , Sher Linda , Akbari Omid , Ekser Burcin , Emamaullee Juliet A.
Published: February 2024

Single cell and spatially resolved ‘omic’ techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome ‘spot’ on tissue sections. In this study, we performed spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) on matched specimens from patients with either histologically normal or advanced fibrosis to establish important aspects of tissue handling, data processing, and downstream analyses of biobanked liver samples. We observed that tissue preservation technique impacts transcriptomic data, especially in fibrotic liver. Single cell mapping of the spatial transcriptome using paired snRNAseq data generated a spatially resolved, single cell dataset with 24 unique liver cell phenotypes. We determined that cell–cell interactions predicted using ligand–receptor analysis of snRNAseq data poorly correlated with cellular relationships identified using spatial transcriptomics. Our study provides a framework for generating spatially resolved, single cell datasets to study gene expression and cell–cell interactions in biobanked clinical samples with advanced liver disease.
Sequential Bayesian-optimized graphene synthesis by direct solar-thermal chemical vapor deposition
Authors: Alghfeli Abdalla , Fisher Timothy S.
Published: February 2024

This work reports the use of a high-flux solar simulator that mimics the solar spectrum and a cold-wall CVD reactor to demonstrate the feasibility of utilizing a renewable energy resource in synthesizing graphene under various conditions. A parametric study of process parameters was conducted using a probabilistic approach. Gaussian process regression serves as a surrogate to establish a prior for Bayesian optimization, and an information acquisition function is employed to identify conditions that yield high-quality products. Backscattered electron images and Raman mapping were used to assess the effects of growth conditions on graphene characteristic sizes, film quality, and uniformity. We report the synthesis of high-quality single-layer graphene (SLG) and AB-stacked bilayer graphene films in a one-step, short-time process with $$I_{D}/I_{G}$$

I
D

/

I
G

ratios of 0.21 and 0.14, respectively. Electron diffraction analysis shows peak intensities that resemble SLG and AB-bilayer graphene with up to 5 and 20 $${\upmu }$$
μ
m grain sizes, respectively. The optical transmissivities of SLG and AB-bilayer graphene fall between 0.959–0.977 and 0.929–0.953, whereas the sheet resistances measured by a 4-point probe with 1 mm spacing are 15.5 ± 4.6 and 3.4 ± 1.5 k$$\Omega$$
Ω
/sq, respectively. Further scale-up of the optimized graphene growth area was achieved by flattening the insolation profile, leading to spatial uniformity up to 13 mm in radius. Direct solar capture for CVD synthesis enable a practical and sustainable option for synthesizing graphene films applicable for photonic and electronic applications.
Concordance of movements and songs enhances receiver responses to multimodal display in the starling
Authors: Rusiecki Stanisław , Ręk Paweł
Published: February 2024

Many animals produce signals that consist of vocalizations and movements to attract mates or deter rivals. We usually consider them as components of a single multimodal signal because they are temporally coordinated. Sometimes, however, this relationship takes on a more complex spatiotemporal character, resembling choreographed music. Timing is important for audio-visual integration, but choreographic concordance requires even more skill and competence from the signaller. Concordance should therefore have a strong impact on receivers; however, little is known about its role in audio-visual perception during natural interactions. We studied the effects of movement and song type concordance in audio-visual displays of the starling, Sturnus vulgaris. Starlings produce two types of movements that naturally appear in specific phrases of songs with a similar temporal structure and amplitude. In an experiment with a taxidermic robotic model, males responded more to concordant audio-visual displays, which are also naturally preferred, than to discordant displays. In contrast, the effect of concordance was independent of the specific combination of movement and song types in a display. Our results indicate that the concordance of movements and songs was critical to the efficacy of the display and suggest that the information that birds gained from concordance could not be obtained by adding information from movements and songs.
Isolation and identification of metallotolerant bacteria with a potential biotechnological application
Authors: Parades-Aguilar Jonathan , Calderon Kadiya , Agustin-Salazar Sarai , Cerruti Pierfrancesco , Ambrogi Veronica , Gamez-Meza Nohemi , Medina-Juarez Luis Angel
Published: February 2024

Mining has led to severe environmental pollution in countries with exhaustive mining production and inadequate industrial waste regulation. Microorganisms in contaminated sites, like mine tailings, have adapted to high concentrations of heavy metals, developing the capacity of reducing or removing them from these environments. Therefore, it is essential to thoroughly characterize bacteria present in these sites to find different ways of bioremediation. In this regard, in this study, an enrichment and isolation procedure were performed to isolate bacteria with lower nutritional requirements and high tolerance to Cu(II) and Fe(II) from two Sonoran River basin mining tails. Two Staphylococcus species and a Microbacterium ginsengisoli strain were isolated and identified from the San Felipe de Jesús mining tail. Also, three strains were isolated from the Nacozari de García mining tail: Burkholderia cenocepacia, Sphingomonas sp. and Staphylococcus warneri. Significant microbiological differences were found between the two sites. All these species exhibited tolerance up to 300 mg/L for Cu (II)–Fe (II) solutions, indicating their capacity to grow in these conditions. Moreover, a consortium of isolated bacteria was immobilized in two different biocomposites and the biocomposite with larger pore size achieved greater bacterial immobilization showcasing the potential of these bacteria in biotechnological applications.
Age at onset of type 1 diabetes between puberty and 30 years old is associated with increased diabetic nephropathy risk
Authors: Lin Yen-Bo ,   Taiwan Diabetes Registry Study Group, Sheu Wayne Huey-Herng , Lo Su-Huey , Yeh Yen-Po , Huang Chien-Ning , Hwu Chii-Min , Hsieh Chang-Hsun , Ou Horng-Yi , Chuang Lee-Ming , Chen Jung-Fu , Chen Yu-Cheng , Peng Yun-Hsing , Chen Szu-Tah , Hsu Shang-Ren , Hsieh Yi-Ling , Chu Chih-Hsun , Lu Chieg-Hsiang , Lee Yau-Jiunn , Chen Hua-Fen , Chen Ching-Chu , Lee Chun-Chuan , Hsiao Pi-Jung , Tsai Shih-Tzer , Chen Samuel , Su Ching-Chieh , Lin Yu-Ling , Bau Cho-Tsan , Liao Chung-Chia , Kuo Tsung-yung , Chen Huey-Jen , Wang Chih-Chien , Cheng Chiu-Jung , Lin Yung-Lung , Chen Shin-Chueh , Chen Chung-Yuan , Huang Hsin-Yang , Chen Jiunn-Rong , Lo Hsiao-Jung , Yu Neng-Chun , Liu Wen-Cheng , Wu Chun-Han , Chen Deng-Wang , Shen De-Chung , Chung Wei-Chen , Chang Tien-Jyun
Published: February 2024

Diabetic nephropathy is a critical complication of patients with type 1 diabetes, while epidemiological studies were scarce among Asian countries. We conducted a cross-sectional study to identify factors associated with diabetic nephropathy by questionnaires, using student’s t-test, chi-square test, and multivariable logistic regression. Among 898 participants, 16.7% had diabetic nephropathy. Compared with non-diabetic nephropathy patients, the patients with diabetic nephropathy had significantly higher percentage with onset age of type 1 diabetes between puberty and under 30 years old (female ≥ 12 or male ≥ 13 years old to 29 years old), longer diabetes duration, having family history of diabetes and diabetic nephropathy, accompanied with hypertension, hyperlipidemia, or coronary artery disease (CAD). Compared with patients with onset age before puberty, the odds of diabetic nephropathy occurrence increased to 1.61 times in patients with onset age between puberty and under 30 years old (p = 0.012) after adjusting diabetes duration. Age of diabetes onset between puberty and under 30 years old, diabetes duration, HbA1c, hospital admission within 3 years, diabetic retinopathy, hypertension, systolic blood pressure (SBP), triglyceride levels, and use of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blockers (ARB) were independent factors associated with diabetic nephropathy Screening for proteinuria is important in daily clinical practice and should be part of diabetes self-management education for patients with type 1 diabetes.
Comparing surface electroenterography measurements between patients suffering from Hirschsprung’s disease and controls: a feasibility study
Authors: Rolleman Nick , Klein Willemijn , Nagtegaal Iris , van Putten Michel , de Blaauw Ivo , Botden Sanne
Published: February 2024

Current diagnostics in Hirschsprung’s disease are often challenging and invasive. This study aims to investigate whether surface electroenterography can non-invasively discern healthy subjects from subjects suffering from Hirschsprung’s disease. Nine healthy subjects (seven children, two adults) and eleven subjects suffering from surgically untreated Hirschsprung’s disease (nine children, two adults) underwent an electroenterography procedure. This procedure consisted of ultrasound-guided placement of surface electrodes on the abdomen covering all parts of the colon, fasting and two 20-min electroenterography measurements separated by a meal. The dominant frequency, magnitude and relative increase (pre- to postprandial) of colonic activity were compared between both groups. The results showed that in the pediatric group, no significant differences in dominant frequency, colonic activity and relative power increase were observed between controls and patients. The adult patients showed decreased colonic motility and relative power increase in the electrodes closest to the distal colon, both when compared to the same electrodes in controls and to the more proximal electrodes of themselves. To conclude, electroenterography measurements in young children is challenging, but the results in adults demonstrate that these measurements can possibly distinguish between controls and Hirschsprung’s patients. Therefore, optimization of electroenterography measurements in young children is necessary.
Deep learning predicts prevalent and incident Parkinson’s disease from UK Biobank fundus imaging
Authors: Tran Charlie , Shen Kai , Liu Kang , Ashok Akshay , Ramirez-Zamora Adolfo , Chen Jinghua , Li Yulin , Fang Ruogu
Published: February 2024

Parkinson’s disease is the world’s fastest-growing neurological disorder. Research to elucidate the mechanisms of Parkinson’s disease and automate diagnostics would greatly improve the treatment of patients with Parkinson’s disease. Current diagnostic methods are expensive and have limited availability. Considering the insidious and preclinical onset and progression of the disease, a desirable screening should be diagnostically accurate even before the onset of symptoms to allow medical interventions. We highlight retinal fundus imaging, often termed a window to the brain, as a diagnostic screening modality for Parkinson’s disease. We conducted a systematic evaluation of conventional machine learning and deep learning techniques to classify Parkinson’s disease from UK Biobank fundus imaging. Our results suggest Parkinson’s disease individuals can be differentiated from age and gender-matched healthy subjects with 68% accuracy. This accuracy is maintained when predicting either prevalent or incident Parkinson’s disease. Explainability and trustworthiness are enhanced by visual attribution maps of localized biomarkers and quantified metrics of model robustness to data perturbations.
Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity
Authors: Rząd Kamila , Gabriel Iwona , Paluszkiewicz Ewa , Kuplińska Aleksandra , Olszewski Mateusz , Chylewska Agnieszka , Dąbrowska Aleksandra M. , Kozłowska-Tylingo Katarzyna
Published: February 2024

Fungal pathogens are considered as serious factors for deadly diseases and are a case of medical concern. Invasive fungal infections also complicate the clinical course of COVID-19, leading to a significant increase in mortality. Furthermore, fungal strains' multidrug resistance has increased the demand for antifungals with a different mechanism of action. The present study aimed to identify antifungal compounds targeting yeast topoisomerase II (yTOPOII) derived from well-known human topoisomerase II (hTOPOII) poisons C-1305 and C-1311. Two sets of derivatives: triazoloacridinones (IKE1-8) and imidazoacridinones (IKE9-14) were synthetized and evaluated with a specific emphasis on the molecular mechanism of action. Our results indicated that their effectiveness as enzyme inhibitors was not solely due to intercalation ability but also as a result of influence on catalytic activity by the formation of covalent complexes between plasmid DNA and yTOPOII. Lysine conjunction increased the strength of the compound's interaction with DNA and improved penetration into the fungal cells. Triazoloacridinone derivatives in contrast to starting compound C-1305 exhibited moderate antifungal activity and at least twice lower cytotoxicity. Importantly, compounds (IKE5-8) were not substrates for multidrug ABC transporters whereas a derivative conjugated with lysine (IKE7), showed the ability to overcome C. glabrata fluconazole-resistance (MIC 32–64 µg mL−1).
Applying the new multi-objective algorithms for the operation of a multi-reservoir system in hydropower plants
Authors: Samare Hashemi Syed Mohsen , Robati Amir , Kazerooni Mohammad Ali
Published: February 2024

The optimal operation of the multi-purpose reservoir system is a difficult, and, sometimes, non-linear problem in multi-objective optimization. By simulating biological behavior, meta-heuristic algorithms scan the decision space and can offer a set of points as a group of solutions to a problem. Because it is essential to simultaneously optimize several competing objectives and consider relevant constraints as the main problem in many optimization problems, researchers have improved their ability to solve multi-objective problems by developing complementary multi-objective algorithms. Because the AHA algorithm is new, its multi-objective version, MOAHA (multi-objective artificial hummingbird algorithm), was used in this study and compared with two novel multi-objective algorithms, MOMSA and MOMGA. Schaffer and MMF1 were used as two standard multi-objective benchmark functions to gauge the effectiveness of the proposed method. Then, for 180 months, the best way to operate the reservoir system of the Karun River basin, which includes Karun 4, Karun 3, Karun 1, Masjed-e-Soleyman, and Gotvand Olia dams to generate hydropower energy, supply downstream demands (drinking, agriculture, industry, environmental), and control flooding was examined from September 2000 to August 2015. Four performance appraisal criteria (GD, S, Δ, and MS) and four evaluation indices (reliability, resiliency, vulnerability, and sustainability) were used in Karun's multi-objective multi-reservoir problem to evaluate the performance of the multi-objective algorithm. All three algorithms demonstrated strong capability in criterion problems by using multi-objective algorithms’ criteria and performance indicators. The large-scale (1800 dimensions) of the multi-objective operation of the Karun Basin reservoir system was another problem. With a minimum of 1441.71 objectives and an average annual hydropower energy manufacturing of 17,166.47 GW, the MOAHA algorithm demonstrated considerable ability compared to the other two. The final results demonstrated the MOAHA algorithm’s excellent performance, particularly in difficult and significant problems such as multi-reservoir systems' optimal operation under various objectives.
Integration of risk factor polygenic risk score with disease polygenic risk score for disease prediction
Authors: Jung Hyein , Jung Hae-Un , Baek Eun Ju , Kwon Shin Young , Kang Ji-One , Lim Ji Eun , Oh Bermseok
Published: February 2024

Polygenic risk score (PRS) is useful for capturing an individual’s genetic susceptibility. However, previous studies have not fully exploited the potential of the risk factor PRS (RFPRS) for disease prediction. We explored the potential of integrating disease-related RFPRSs with disease PRS to enhance disease prediction performance. We constructed 112 RFPRSs and analyzed the association of RFPRSs with diseases to identify disease-related RFPRSs in 700 diseases, using the UK Biobank dataset. We uncovered 6157 statistically significant associations between 247 diseases and 109 RFPRSs. We estimated the disease PRSs of 70 diseases that exhibited statistically significant heritability, to generate RFDiseasemetaPRS—a combined PRS integrating RFPRSs and disease PRS—and compare the prediction performance metrics between RFDiseasemetaPRS and disease PRS. RFDiseasemetaPRS showed better performance for Nagelkerke’s pseudo-R2, odds ratio (OR) per 1 SD, net reclassification improvement (NRI) values and difference of R2 considered by variance of R2 in 31 out of 70 diseases. Additionally, we assessed risk classification between two models by examining OR between the top 10% and remaining 90% individuals for the 31 diseases; RFDiseasemetaPRS exhibited better R2, NRI and OR than disease PRS. These findings highlight the importance of utilizing RFDiseasemetaPRS, which can provide personalized healthcare and tailored prevention strategies.