bluuebunny/crossref_metadata_2025 huggingface dataset:
A single-cell multi-omic and spatial atlas of B-cell lymphomas reveals differentiation drives intratumor heterogeneity
Authors: Fitzgerald Donnacha , Roider Tobias , Baertsch Marc-Andrea , Kibler Artur , Horlova Anastasiia , Chung Erin , Vöhringer Harald , Mathioudaki Anna , Budeus Bettina , Passerini Verena , Knoll Mareike , Mammen Johannes , Li Linsha , Caillé Léandra , Czernilofsky Felix , Bruch Peter-Martin , Liebers Nora , Meyer-Bender Matthias , Siebert Reiner , Weigert Oliver , Zaugg Judith , Nolan Garry , Seifert Marc , Dietrich Sascha , Huber Wolfgang
Published: November 2023

Intratumor heterogeneity underpins cancer pathogenesis and evolution, although it is typically considered independent from the differentiation processes that drive physiological cell-type diversity. As cancer types and subtypes arise from different cell types, we investigated whether cellular differentiation influences intratumor heterogeneity. Nodal B-cell non-Hodgkin lymphomas are a diverse set of cancers originating from different stages of B-cell maturation. Through single-cell transcriptome and surface epitope profiling (CITE-Seq) of diffuse large B-cell, mantle cell, follicular, and marginal zone lymphomas in addition to reactive lymph nodes from 51 patients, we found multiple B-cell maturation states within tumors. Intratumor maturation states emerged from the same clone, revealing divergent differentiation from a shared cell of origin. Maturation state composition varied across subtypes and tumors, which encompassed mixed cell-of-origin diagnostic subtypes. Through highly multiplexed immunohistochemistry (CODEX) of samples from 19 of these patients, we found that intratumor maturation states inhabited distinct spatial niches, displaying cellular interactions and regulatory networks typical of their maturation states while harboring different genetic variants. By deconvoluting intratumor maturation states from a microarray dataset of 507 patients, we identified risk groups within diagnoses with striking differences in survival, including IgM memory-enriched germinal center B-cell (M = 1.9 vs >10 years, p = 0.00039) and activated B-cell (M = 2.4 vs 9.6 years, p = 0.016) diffuse large B-cell lymphoma, and dark zone-enriched follicular lymphoma (M = 8.6 vs 13 years; p = 0.0019). Our findings reveal cellular differentiation remains plastic in B-cell lymphomas, driving tumor variation, evolution, and response.

Key Points

Cellular differentiation remains plastic in B-cell lymphomas, driving tumor variation, evolution, and response.

Intratumor maturation states occupy unique immune niches, harbor distinct genetic variants, and are tied to different survival outcomes.
IC-VAE: A Novel Deep Learning Framework for Interpreting Multiplexed Tissue Imaging Data
Authors: Nguyen Huy , Vuong Hy , Truong Thao , Pham Son
Published: November 2023

Abstract

Interpreting protein expression in multiplexed tissue imaging data presents a significant challenge due to the high dimensionality of the resulting images, the variety of intracellular structures, cell shapes resulting from 2-D tissue sectioning, and the presence of technological noise and imaging artifacts. Here, we introduce the Information-Controlled Variational Autoencoder (IC-VAE), a deep generative model designed to tackle this challenge. The contribution of IC-VAE to the VAE framework is the ability to control the shared information among latent subspaces. We use IC-VAE to factorize each cell’s image into its true protein expression, various cellular components, and background noise, while controlling the shared information among some of these components. Compared with other normalization methods, this approach leads to superior results in downstream analysis, such as analyzing the expression of biomarkers, classification for cell types, or visualizing cell clusters using t-SNE/UMAP techniques.
Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner
Authors: Shimonty Anika , Pin Fabrizio , Prideaux Matt , Peng Gang , Huot Joshua R , Kim Hyeonwoo , Rosen Clifford J , Spiegelman Bruce M , Bonewald Lynda F
Published: November 2023

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lackingFndc5(KO), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.
A method for evaluating hunger and thirst in monkeys by measuring blood ghrelin and osmolality levels
Authors: Suwa Yuki , Kunimatsu Jun , Kamata Akua , Matsumoto Masayuki , Yamada Hiroshi
Published: November 2023

Hunger and thirst drive animals’ consumption behavior and regulate their decision-making regarding rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and related the thirst states to risky decisions for fluid rewards. However, hunger assessments in monkeys have been poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate subject performances, how these two physiological needs are satisfied in captive monkeys remains unclear. Here, we measured blood ghrelin levels and osmolality for hunger and thirst, respectively, in four captive macaques. Using enzyme-linked immunosorbent assay, we found that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (withad libitumwater), which is a typical controlled food access condition. One hour after consuming the regular dry meal, the value decreased in three out of four monkeys to within the range of individual blood ghrelin levels. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming regular dry meals with no water access. Thus, ghrelin and osmolality may provide a precise reflection of the physiological states of individual monkeys for hunger and thirst, suggesting that these indices can be used as a tool for monitoring hunger and thirst levels that mediate the animal’s decision-making for consuming rewards.
Using natural language processing to extract plant functional traits from unstructured text
Authors: Domazetoski Viktor , Kreft Holger , Bestova Helena , Wieder Philipp , Koynov Radoslav , Zarei Alireza , Weigelt Patrick
Published: November 2023

Functional plant ecology aims to understand how functional traits govern the distribution of species along environmental gradients, the assembly of communities, and ecosystem functions and services. The rapid rise of functional plant ecology has been fostered by the mobilization and integration of global trait datasets, but significant knowledge gaps remain about the functional traits of the ∼380,000 vascular plant species worldwide. The acquisition of urgently needed information through field campaigns remains challenging, time-consuming and costly. An alternative and so far largely untapped resource for trait information is represented by texts in books, research articles and on the internet which can be mobilized by modern machine learning techniques.

Here, we propose a natural language processing (NLP) pipeline that automatically extracts trait information from an unstructured textual description of a species and provides a confidence score. To achieve this, we employ textual classification models for categorical traits and question answering models for numerical traits. We demonstrate the proposed pipeline on five categorical traits (growth form, life cycle, epiphytism, climbing habit and life form), and three numerical traits (plant height, leaf length, and leaf width). We evaluate the performance of our new NLP pipeline by comparing results obtained using different alternative modeling approaches ranging from a simple keyword search to large language models, on two extensive databases, each containing more than 50,000 species descriptions.

The final optimized pipeline utilized a transformer architecture to obtain a mean precision of 90.8% (range 81.6-97%) and a mean recall of 88.6% (77.4-97%) on the categorical traits, which is an average increase of 21.4% in precision and 57.4% in recall compared to a standard approach using regular expressions. The question answering model for numerical traits obtained a normalized mean absolute error of 10.3% averaged across all traits.

The NLP pipeline we propose has the potential to facilitate the digitalization and extraction of large amounts of plant functional trait information residing in scattered textual descriptions. Additionally, our study adds to an emerging body of NLP applications in an ecological context, opening up new opportunities for further research at the intersection of these fields.
Engineering Modular and Tunable Single Molecule Sensors by Decoupling Sensing from Signal Output
Authors: Grabenhorst Lennart , Pfeiffer Martina , Schinkel Thea , Kümmerlin Mirjam , Maglic Jasmin B. , Brüggenthies Gereon A. , Selbach Florian , Murr Alexander T. , Tinnefeld Philip , Glembockyte Viktorija
Published: November 2023

Biosensors play key roles in medical research and diagnostics, but there currently is a lack of sensing platforms that combine easy adaptation to new targets, strategies to tune the response window to relevant analyte concentration ranges and allow for the incorporation of multiple sensing elements to benefit from multivalency. Utilizing a DNA origami nanostructure as a scaffold for arranging the different sensor components, we here propose an approach for the development of modular and tunable single-molecule sensors capable of detecting a variety of biomolecular targets such as nucleic acids, antibodies and restriction enzymes while offering mechanisms to tune the dynamic window, the specificity, and the cooperativity of the sensor.
Novel tri-segmented rhabdoviruses: A data mining expedition unveils the cryptic diversity of cytorhabdoviruses
Authors: Bejerman Nicolás , Dietzgen Ralf Georg , Debat Humberto
Published: November 2023

Cytorhabdoviruses (genusCytorhabdovirus, familyRhabdoviridae) are plant-infecting viruses with enveloped, bacilliform virions. Established members of the genusCytorhabdovirushave unsegmented single-stranded negative-sense RNA genomes (ca. 10-16 kb) which encode four to ten proteins. Here, by exploring large publicly available metatranscriptomics datasets, we report the identification and genomic characterization of 93 novel viruses with genetic and evolutionary cues of cytorhabdoviruses. Strikingly, five unprecedented cytorhabdoviruses with tri-segmented genomes were also identified. This finding represents the first tri-segmented viruses in the familyRhabdoviridae. Interestingly, the nucleocapsid and polymerase were the only typical rhabdoviral proteins encoded by those tri-segmented viruses, whereas in three of them, a protein similar to the emaravirus (familyFimoviridae) silencing suppressor was found, while the other predicted proteins had no matches in any sequence databases. Genetic distance and evolutionary insights suggest that all these novel viruses may represent members of novel species. Phylogenetic analyses, of both novel and previously classified plant rhabdoviruses, provide compelling support for the division of the genusCytorhabdovirusinto three distinct genera. This proposed reclassification not only enhances our understanding of the evolutionary dynamics within this group of plant rhabdoviruses but also illuminates the remarkable genomic diversity they encompass. This study not only represents a significant expansion of genomics of cytorhabdoviruses that will enable future research on the evolutionary peculiarity of this genus, but also shows the plasticity in the rhabdovirus genome organization with the discovery of tri-segmented members with a unique evolutionary trajectory.
Sphingosine induction of thePseudomonas aeruginosahemolytic phospholipase C/sphingomyelinase, PlcH
Authors: Mackinder Jacob R. , Hinkel Lauren A. , Schutz Kristin , Eckstrom Korin , Fisher Kira , Wargo Matthew J.
Published: November 2023

The hemolytic phospholipase C, PlcH, is an important virulence factor forPseudomonas aeruginosa. PlcH preferentially hydrolyzes sphingomyelin and phosphatidylcholine and this hydrolysis activity can drives tissue damage, inflammation, and interferes with the oxidative burst of immune cells. Among other contributors, transcription ofplcHwas previously shown to be induced by phosphate starvation via PhoB and by the choline metabolite, glycine betaine, via GbdR. Here, we show that sphingosine can induceplcHtranscription and resultant secreted PlcH enzyme activity. This induction is dependent on the sphingosine-sensing transcription regulator SphR. The SphR induction ofplcHoccurs from the promoter for the gene upstream ofplcHthat encodes the neutral ceramidase, CerN, and transcriptional read-through of thecerNtranscription terminator. Evidence for these conclusions come from mutation of the SphR binding site in thecerNpromoter, mutation of thecerNterminator, enhancement ofcerNtermination by adding therrnBterminator, and RT-PCR showing that the intergenic region betweencerNandplcHis made as RNA during sphingosine, but not choline, induction. We also observe that, like glycine betaine induction, sphingosine induction ofplcHis under catabolite repression control, which likely explains why such induction was not seen in other studies using sphingosine in rich media. The addition of sphingosine as a novel inducer for PlcH points to regulation ofplcHtranscription as a site for integration of multiple host-derived signals.
Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators
Authors: Shao Qian , Duong Tuong Nghi , Park Inji , Nomura Daniel K.
Published: November 2023

14-3-3 proteins have the unique ability to bind and sequester a multitude of diverse phosphorylated signaling proteins and transcription factors. Many previous studies have shown that 14-3-3 interactions with specific phosphorylated substrate proteins can be enhanced through small-molecule natural product or fully synthetic molecular glue interactions. However, enhancing 14-3-3 interactions with both therapeutically intractable transcription factor substrates as well as potential neo-substrates to sequester and inhibit their function has remained elusive. One of the 14-3-3 proteins, 14-3-3σ or SFN, has a cysteine C38 at the substrate binding interface near sites where previous 14-3-3 molecular glues have been found to bind. In this study, we screened a fully synthetic cysteine-reactive covalent ligand library to identify molecular glues that enhance interaction of 14-3-3σ with not only druggable transcription factors such as estrogen receptor (ERα), but also challenging oncogenic transcription factors such as YAP and TAZ that are part of the Hippo transducer pathway. We identified a hit EN171 that covalently targets 14-3-3 to enhance 14-3-3 interactions with ERα, YAP, and TAZ leading to impaired estrogen receptor and Hippo pathway transcriptional activity. We further demonstrate that EN171 could not only be used as a molecular glue to enhance native protein interactions, but also could be used as a covalent 14-3-3 recruiter in heterobifunctional molecules to sequester nuclear neo-substrates such as BRD4 into the cytosol. Overall, our study reveals a covalent ligand that acts as a novel 14-3-3 molecular glue for challenging transcription factors such as YAP and TAZ and also demonstrates that these glues can be potentially utilized in heterobifunctional molecules to sequester nuclear neo-substrates out of the nucleus and into the cytosol to enable targeted protein localization.
ContactBlot: Microfluidic Control and Measurement of Cell-Cell Contact State to Assess Contact-Inhibited ERK Signaling
Authors: Zhang Yizhe , Naguro Isao , Ryuno Hiroki , Herr Amy E.
Published: November 2023

Extracellular signal-regulated kinase (ERK) signaling is essential to regulated cell behaviors, including cell proliferation, differentiation, and apoptosis. The influence of cell-cell contacts on ERK signaling is central to epithelial cells, yet few studies have sought to understand the same in cancer cells, particularly with single-cell resolution. To acquire same-cell measurements of both phenotypic (cell-contact state) and targeted-protein profile (ERK phosphorylation), we prepend high-content, whole-cell imaging prior to endpoint cellular-resolution western blot analyses for each of hundreds of individual HeLa cancer cells cultured on that same chip, which we callcontactBlot. By indexing the phosphorylation level of ERK in each cell or cell-cluster to the imaged cell-contact state, we compare ERK signaling between isolated and in-contact cells. We observe attenuated (∼2×) ERK signaling in HeLa cells which are in-contactversusisolated. Attenuation is sustained when the HeLa cells are challenged with hyperosmotic stress. Our findings show the impact of cell-cell contacts on ERK activation with isolated and in-contact cells, while introducing a multi omics tool for control and scrutiny of cell-cell interactions.
Targeting Rab-RILPL Interactions as a Strategy to Downregulate Pathogenic LRRK2 in Parkinson’s Disease
Authors: Alexander Krista K. , Naaldijk Yahaira , Fasiczka Rachel , Brahmia Besma , Chen Tiancheng , Hilfiker Sabine , Kennedy Eileen J.
Published: November 2023

Familial Parkinson’s disease (PD) is frequently linked to multiple disease-causing mutations within Leucine-Rich Repeat Protein Kinase 2 (LRRK2), leading to aberrant kinase activity. Multiple pathogenic effects of enhanced LRRK2 activity have been identified including loss of cilia and centrosomal cohesion defects. When phosphorylated by LRRK2, Rab8a and Rab10 bind to phospho-specific RILPL effector proteins. RILPL-mediated accumulation of pRabs proximal to the mother centriole is critical for initiating deficits in ciliogenesis and centrosome cohesion mediated by LRRK2. We hypothesized that Rab-derived phospho-mimics may serve to block phosphorylated Rab proteins from docking with RILPL in the context of hyperactive LRRK2 mutants. This would serve as an alternative strategy to downregulate pathogenic signaling mediated by LRRK2, rather than targeting LRRK2 kinase activity itself. To test this theory, we designed a series of constrained peptides mimicking phosphorylated Switch II derived from Rab8. These RILPL interacting peptides, termed RIP, were further shown to permeate cells. Further, several peptides were found to bind RILPL2 and restore ciliogenesis and centrosomal cohesion defects in cells expressing PD-associated mutant LRRK2. This research demonstrates the utility of constrained peptides as downstream inhibitors to target pathogenic LRRK2 activity and may provide an alternative approach to target specific pathways activated by LRRK2.
Heritability within groups is uninformative about differences among groups: cases from behavioral, evolutionary, and statistical genetics
Authors: Schraiber Joshua G. , Edge Michael D.
Published: November 2023

Without the ability to control or randomize environments (or genotypes), it is difficult to determine the degree to which observed phenotypic differences between two groups of individuals are due to genetic vs. environmental differences. However, some have suggested that these concerns may be limited to pathological cases, and methods have appeared that seem to give—directly or indirectly—some support to claims that aggregate heritable variation within groups can be related to heritable variation among groups. We consider three families of approaches: the “between-group heritability” sometimes invoked in behavior genetics, the statisticPSTused in empirical work in evolutionary quantitative genetics, and methods based on variation in ancestry in an admixed population, used in anthropological and statistical genetics. We take up these examples to show mathematically that information on within-group genetic and phenotypic information in the aggregate cannot separate among-group differences into genetic and environmental components, and we provide simulation results that support our claims. We discuss these results in terms of the long-running debate on this topic.
Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice
Authors: Yamamoto Naoki , Yokose Jun , Ramesh Kritika , Kitamura Takashi , Ogawa Sachie K.
Published: November 2023

Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus. In this study, using a molecular marker for Vb and retrograde tracers, we identified that the outer layer of Vb in the medial EC (MEC) neurons directly project to both dorsal and ventral hippocampal DG, with a significant preference for the ventral DG. In contrast to the distribution of DG-projecting Vb cells, anterior thalamus-projecting Vb cells are distributed through the outer to the inner layer of Vb. Furthermore, dual tracer injections revealed that DG-projecting Vb cells and anterior thalamus-projecting Vb cells are distinct populations. These results suggest that the roles of MEC Vb neurons are not merely limited to the formation of EC-HPC loop circuits, but rather contribute to multiple neural processes for learning and memory.
Phylogenetic diversity of flowering plants declines throughout the growing season across a subalpine elevational gradient
Authors: Veldhuisen Leah N , Enquist Brian J , Dlugosch Katrina M
Published: November 2023

Co-flowering is a potential facilitative mechanism for plants to overcome pollinator declines and phenological mismatches by attracting more pollinators to a multi-species patch. Due to associated competition, facilitation is expected to be more beneficial among more distantly related plants that compete less, and more prevalent in stressful conditions where benefits outweigh potential costs. We test a novel set of predictions that follow from these hypotheses, including that modules of co-flowering species in montane plant communities will be associated with i) increased fitness, ii) phylogenetic overdispersion, and ii) higher elevations. We quantified flowering phenology and fitness of plants across an elevational gradient in the Colorado Rocky Mountains, identified co-flowering modules using a network approach, and analyzed the phylogenetic distribution of co-flowering modules. We found that fitness correlated positively with co-flowering across elevations, but the correlation was strongest at high-elevation sites. Phylogenetic dispersion increased with elevation but declined throughout the growing season. Late-season modules were more underdispersed at all elevations than early-season modules. By combining analyses of phenological timing, network structure, environmental stress, fitness, and phylogenetic patterns, our results reveal that plant communities may lose phylogenetic diversity as conditions become hotter and drier and climate change alters flowering phenology and pollination networks.
Tree-structured topic modelling of single-cell gene expression data uncovers hierarchical relationships between immune cell types
Authors: Ye Patricia E. , Zhang Yichen , Klein Geltink Ramon I. , Park Yongjin P.
Published: November 2023

Immune cells undergo a series of differentiation steps following a lineage-tree structure stemming from hematopoietic stem cells. During differentiation of immune cells in both homeostasis and pathological processes, many gene regulatory mechanisms are shared by fully differentiated immune cell sub-types. In order to characterize these features quantitatively, we proposeLaRCH, a tree-structured embedded topic model. In this model, single-cell gene expression profiles are represented by a mixture of topics consisting of latent features that follow an underlying tree structure, mirroring that of cellular differentiation–nested cluster structures. We present findings of our model trained on simulated single-cell RNA sequencing (scRNA-seq) based on cell-sorted bulk RNA-seq data as well as on a scRNA-seq dataset of over 1.2 million cells from healthy individuals and individuals diagnosed with systemic lupus erythematosus (SLE). The cellular topic profiles estimated by our model markedly improve clustering accuracy over traditional latent variable models and illustrate transcriptomic differences between SLE phenotypes, revealing a pivotal role of multiple immune cell types in disease progression and relapse. Ultimately,LaRCHcaptures the hierarchical context between cellular subtypes by simultaneously identifying shared and distinct latent features amongst subsets of heterogeneous samples of cells.
Protein language models enable prediction of polyreactivity of monospecific, bispecific, and heavy-chain-only antibodies
Authors: Yu Xin , Vangjeli Kostika , Prakash Anusha , Chhaya Meha , Stanley Samantha J , Cohen Noah , Huang Lili
Published: November 2023

Early assessment of antibody off-target binding is essential for mitigating developability risks such as fast clearance, reduced efficacy, toxicity, and immunogenicity. The baculovirus particle (BVP) binding assay has been widely utilized to evaluate polyreactivity of antibodies. As a complementary approach, computational prediction of polyreactivity is desirable for counter-screening antibodies fromin silicodiscovery campaigns. However, there is a lack of such models. Herein, we present the development of an ensemble of three deep learning models based on two pan-protein foundational protein language models (ESM2 and ProtT5) and an antibody-specific protein language model (Antiberty). These models were trained in a transfer learning network to predict the outcomes in the BVP assay and the bovine serum albumin (BSA) binding assay which was developed as a complement to the BVP assay. The training was conducted on a large dataset of antibody sequences augmented with experimental conditions, which were collected through a highly efficient application system. The resulting models demonstrated robust performance on normal mAbs (monospecific with heavy and light chain), bispecific Abs, and single-domain Fc (VHH-Fc). Protein language models outperformed a model built using molecular descriptors calculated from AlphaFold 2 predicted structures. Embeddings from the antibody-specific and foundational protein language models resulted in similar performance. To our knowledge, this represents the first application of protein language models to predict assay data on bispecifics and VHH-Fcs. Our study yields valuable insights on building infrastructures to support machine learning activities and training models for critical assays in antibody discovery.
Biomimetic model of corticostriatal micro-assemblies discovers new neural code
Authors: Pathak Anand , Brincat Scott L. , Organtzidis Haris , Strey Helmut H. , Senneff Sageanne , Antzoulatos Evan G. , Mujica-Parodi Lilianne R. , Miller Earl K. , Granger Richard
Published: November 2023

Although computational models have deepened our understanding of neuroscience, it is still highly challenging to link actual low-level physiological activity (spiking, field potentials) and biochemistry (transmitters and receptors) with high-level cognitive abilities (decision-making, working memory) nor with corresponding disorders. We introduce an anatomically-organized multi-scale model directly generating simulated physiology from which extended neural and cognitive phenomena emerge. The model produces spiking, fields, phase synchronies, and synaptic change, directly generating working memory, decisions, and categorization, all of which were then validated on extensive experimental macaque data from which the model received zero prior training of any kind. Moreover, the simulation uncovered a previously unknown neural code specifically predicting upcoming erroneous (“incongruous”) behaviors, also subsequently confirmed in empirical data. The biomimetic model thus directly and predictively links novel decision and reinforcement signals, of computational interest, with novel spiking and field codes, of potential behavioral and clinical relevance.
Optimizing mixed sample analysis as a step to comprehensive desease screening: a pilot study
Authors: Krasnicanova Lucia , Forgacova Natalia , Sedlackova Tatiana , Budis Jaroslav , Gazdarica Juraj , Repiska Vanda , Szemes Tomas
Published: November 2023

Background

Lynch Syndrome (LS) is an autosomal dominant hereditary syndrome associated with a diverse range of cancer types. Despite being one of the most prevalent hereditary cancer syndromes, the detection of LS remains challenging due to the absence of well-defined diagnostic criteria which would be able to select all patients who should undergo testing for LS and the limitations of existing screening methods. The implementation of an efficient screening program capable of accurately detecting the majority of LS cases remains a topic of continuous discussion in the scientific literature, with recent studies emphasizing the significance of a universal screening program.

Methods

Our study aimed to develop and optimize a cost-effective universal screening method for detecting mutation in the mismatch repair (MMR) genes through mixed sample analysis. We tested five approaches in terms of the use of biological material and the analysis of mixed samples.

Results

Each approach successfully detected a specific Lynch-associated pathogenic variant in mixed in the pooled samples with frequency 5.00%, with the lowest allelic fraction recorded at 3.04%. Approach 2, which involved isolating DNA from each patient individually, demonstrated the highest average allelic fraction (7.04%). However, considering financial and time requirements, approach 1, where DNA was isolated only after mixing aliquots of whole blood, proved to be the most favorable.

Conclusion

The findings of our study present a promising opportunity to improve LS detection. The identification of LS not only has the potential to prevent cancer-related morbidity and mortality but also facilitates continued progress in understanding the primary prevention of cancer.
Opportunities and new developments for the study of surfaces and interfaces in soft condensed matter at the SIRIUS beamline of Synchrotron SOLEIL
Authors: Hemmerle Arnaud , Aubert Nicolas , Moreno Thierry , Kékicheff Patrick , Heinrich Benoît , Spagnoli Sylvie , Goldmann Michel , Ciatto Gianluca , Fontaine Philippe
Published: November 2023

The SIRIUS beamline of Synchrotron SOLEIL is dedicated to X-ray scattering and spectroscopy of surfaces and interfaces, covering the tender to mid-hard X-ray range (1.1–13 keV). The beamline has hosted a wide range of experiments in the field of soft interfaces and beyond, providing various grazing-incidence techniques such as diffraction and wide-angle scattering (GIXD/GIWAXS), small-angle scattering (GISAXS) and X-ray fluorescence in total reflection (TXRF). SIRIUS also offers specific sample environments tailored for in situ complementary experiments on solid and liquid surfaces. Recently, the beamline has added compound refractive lenses associated with a transfocator, allowing for the X-ray beam to be focused down to 10 µm × 10 µm while maintaining a reasonable flux on the sample. This new feature opens up new possibilities for faster GIXD measurements at the liquid–air interface and for measurements on samples with narrow geometries.
Do audit attributes impact earnings quality? Evidence from India
Authors: Verma Deepak , Dawar Varun , Chaudhary Pankaj
Published: November 2023

Purpose

The present study's goal is to analyze the impact of audit quality (AQ) on earnings quality (EQ) using different audit attributes. The study shows empirical evidence from India, considered an emerging market.

Design/methodology/approach

The sample selected represents the 376 non-financial firms listed on the Bombay Stock Exchange (BSE). With a 20-year time frame, the authors used the absolute value of discretionary accruals (McNichols, 2002) (DA) as a proxy for EM, which is inversely related to EQ. The authors analyzed data using OLS, fixed effect (FE), 2SLS and Panel-IV estimators.

Findings

The authors found that most audit attributes positively affect EQ. In the Indian context, joint auditor (JA), auditor size (A_SIZE), auditor fee (A_FEE) and auditor tenure (A_TENURE) have a negative association with EM indicating high EQ. In contrast, auditor rotation (A_ROTATON) positively affects EM confirming low EQ.

Research limitations/implications

The present study uses Big-4 and its member firms as a proxy of auditor size (A_SIZE); instead, other bases may be taken for it, like the dominant audit firms in a particular industry in sample data, etc. The authors have started audit tenure from the base year, i.e. 2001, which may ignore the association of auditor and auditee just before 2001.

Practical implications

The study findings would enhance policymakers' willingness to prepare appropriate regulations regarding JAs and auditor rotation, which might improve financial market efficiency and reduce financial fraud among Indian corporates.

Originality/value

To the best of the authors' knowledge, this is the first study to incorporate “Joint Auditor” (JA) as a proxy for audit quality in the Indian context, which might significantly contribute to the literature.
Blockchain technology in foreign trade management: which blockchain alternative is more suitable?
Authors: Topcu Yunus Emre , Can İbrahim Enes , Özçınar Atilla
Published: November 2023

Purpose

This study aims to determine the order of importance of blockchain technology gains for foreign trade management. The second aim of the research is to select the most suitable blockchain type for the foreign trade process.

Design/methodology/approach

The data required for the research analysis were collected through comparison matrices scored by foreign trade experts. The data were analyzed with the analytical hierarchy process method, and the gains of blockchain technology for the foreign trade process were prioritized. Finally, the most suitable type of blockchain technology was selected with the PROMETHEE method.

Findings

As a result of the study, subject matter experts perceived that the most critical blockchain gain for the foreign trade process would be cost savings. In addition, it has been observed that the general trade process differs compared to the logistics and payment processes. Finally, open blockchain was the most suitable blockchain type for foreign trade processes.

Research limitations/implications

In this study, the positive gains of blockchain technology are considered. In future studies, it is recommended to consider the existing negative factors to be able to use blockchain technology in foreign trade processes. In addition, it is suggested to conduct a study by dividing foreign trade into two, import and export.

Practical implications

All stakeholders who want to integrate blockchain technology into their foreign trade processes, including foreign trade companies, software developers, policymakers and international institutions, can benefit from the results of this study. A blockchain technology software created for foreign trade management can be shaped according to the results of this study.

Originality/value

Although the gains that blockchain technology provides to foreign trade processes are frequently emphasized in the literature, which gain would be greater has not been examined. The lack of an answer to the issue of how blockchain technology should be designed for foreign trade processes has been the missing part of the relevant literature. To the best of the authors’ knowledge, this study is the first experimental study in the literature that prioritizes blockchain gains and selects the appropriate blockchain type for foreign trade processes.
Aerodynamic optimization of mixed platoon Ahmed body vehicles based on response surface method
Authors: Luo Jianbin , Tie Yuanhao , Mi Ke , Pan Yajuan , Tang Lifei , Li Yuan , Xu Hongxiang , Liu Zhonghang , Li Mingsen , Jiang Chunmei
Published: November 2023

Purpose

The purpose of this paper is to investigate the optimal average drag coefficient of the Ahmed body for mixed platoon driving under crosswind and no crosswind conditions using the response surface optimization method. This study has extraordinary implications for the planning of future intelligent transportation.

Design/methodology/approach

First, the single vehicle and vehicle platoon models are validated. Second, the configuration with the lowest average drag coefficient under the two conditions is obtained by response surface optimization. At the same time, the aerodynamic characteristics of the mixed platoon driving under different conditions are also analyzed.

Findings

The configuration with the lowest average drag coefficient under no crosswind conditions is 0.3 L for longitudinal spacing and 0.8 W for lateral spacing, with an average drag coefficient of 0.1931. The configuration with the lowest average drag coefficient under crosswind conditions is 10° for yaw angle, 0.25 L for longitudinal spacing, and 0.8 W for lateral spacing, with an average drag coefficient of 0.2251. Compared to the single vehicle, the average drag coefficients for the two conditions are reduced by 25.1% and 41.3%, respectively.

Originality/value

This paper investigates the lowest average drag coefficient for mixed platoon driving under no crosswind and crosswind conditions using a response surface optimization method. The computational fluid dynamics (CFD) results of single vehicle and vehicle platoon are compared and verified with the experimental results to ensure the reliability of this study. The research results provide theoretical reference and guidance for the planning of intelligent transportation.
The human consequences of economic sanctions
Authors: Rodríguez Francisco
Published: November 2023

Purpose

The use of economic sanctions has grown dramatically in recent decades. Nevertheless, many arguments are presented in the public policy space regarding their effects on target populations. The author presents the first systematic analysis of the effects of sanctions on living conditions in target countries.

Design/methodology/approach

This paper provides a comprehensive survey and assessment of the literature on the effects of economic sanctions on living standards in target countries. The author identifies 31 studies that apply quantitative econometric or calibration methods to cross-country and national data to assess the impact of economic sanctions on indicators of human and economic development. The author provides in-depth discussions of three sanctions episodes—Iran, Afghanistan and Venezuela—that illustrate the channels through which sanctions affect living conditions in target countries.

Findings

Of the 31 studies, 30 find that sanctions have negative effects on outcomes ranging from per capita income to poverty, inequality, mortality and human rights. The author provides new results showing that 54 countries—27% of all countries and 29% of the world economy— are sanctioned today, up from only 4% of countries in the 1960s. In the three cases discussed, sanctions that restricted the access of governments to foreign exchange limited the ability of states to provide essential public goods and services and generated substantial negative spillovers on private sector and nongovernmental actors.

Originality/value

This is the first literature survey that systematically assesses the quantitative evidence on the effect of sanctions on living conditions in target countries.
Trade effects of liner shipping across world regions
Authors: Del Rosal Ignacio
Published: November 2023

Purpose

Liner shipping plays a crucial role in facilitating the movement of manufactured goods around the world. While previous literature has shown that liner shipping is an important trade driver, potential differences across trade routes and world regions have not as yet been explored. This paper examines whether the impact of liner shipping on bilateral trade flows differs significantly across world regions, as well as exploring other geographical patterns.

Design/methodology/approach

Using state-of-the-art gravity modelling, this paper investigates the impact of the UNCTAD's Liner Shipping Bilateral Connectivity Index on bilateral trade in manufactured goods using a comprehensive database of disaggregated trade data for the period from 2006 to 2019.

Findings

The results show that the trade effect of liner shipping is greater in long-distance and interregional bilateral flows. For some regions, such as North America and Oceania, the effect is greater than the world average, while for others, such as Africa and South America, the effect is significantly smaller. The trade effects of liner shipping connectivity on the main east–west routes are average, but clear asymmetry emerges when analysing China's inward and outward trade flows separately.

Originality/value

The results of this paper show that the major east–west routes determine the baseline trade effects of liner shipping, demonstrate that some north–south trades such as those involving Oceania generate larger trade effects and confirm that the trade effects of liner shipping can be improved for some world regions such as South America and Africa.
Leadership and managerial challenges to ensure agile management as a method to enable business success: a Delphi study of the Slovenian health organisations
Authors: Roblek Vasja , Dimovski Vlado , Jovanov Oblak Kristjan , Meško Maja , Peterlin Judita
Published: November 2023

Purpose

This study aims to apply the Delphi method to explore the possibilities for implementing agility management concepts in Slovenian health-care organisations.

Design/methodology/approach

The research is based on a qualitative Delphi study encompassing 15 employees in different Slovenian health-care organisations.

Findings

Slovenian health-care organisations need to be more agile currently. For this reason, it is necessary to begin with organisational changes and organisational learning concepts to educate employees about the meaning and content of agile processes. It is essential to ensure that accepting employee mistakes and offering help to employees becomes normal practice, and it is necessary to ensure the greater trust of the management towards the employees.

Originality/value

The research empowers health-care professionals with new management and leadership concepts, such as agile management, sustainable leadership and leadership development methods in health care.
Fintech development and environmental sustainability: Does income inequality matter?
Authors: Vu Nam Thanh , Bui Hung Quang , Pham Tuan Anh , Vo Duc Hong
Published: November 2023

This paper investigates whether and how fintech development is associated with environmental quality. A machine learning technique—the principal component analysis (PCA), is adopted to construct an index that measures fintech development. The two‐step system generalised method of moments (GMM) addresses the potential endogeneity in the established nexus. Analysing a panel of 42 countries from 2012 to 2021, we found that fintech development can improve environmental quality by encouraging low‐carbon energy consumption and mitigating anthropogenic polluting emissions. Our analysis further reveals that high‐income inequality, a socioeconomic issue, counteracts the favourable features of fintech development on the environment. Our findings are robust across various additional analyses and environmental quality indicators. This study, therefore, contributes to the scarce but growing literature on the fintech‐environment nexus.
Financial Analyst Coverage and Corporate Environmental Disclosure
Authors: Benlemlih Mohammed , Bitar Mohammad , Ouadghiri Imane El , Peillex Jonathan
Published: November 2023

Consistent with the monitoring function played by financial analysts, we find that greater analyst coverage leads to the same extent of improvement in the quantity and quality of environmental information disclosed by the firm. This result is remarkably robust after conducting a difference‐in‐differences analysis that exploits brokerage closures and mergers as an exogenous decrease in analyst coverage, as well as using an instrumental variable approach. The positive influence of analyst coverage on corporate environmental disclosure is particularly evident for firms that cause high environmental damage, firms with low information asymmetry and those followed by analysts with superior experience, accuracy and reputation. Taken together, our empirical findings provide new insights into the bright side effect of analyst coverage on corporate environmental‐related activities.
The effect of hand fine motor skills on peritoneal dialysis‐related peritonitis
Authors: Dogan Ibrahim , Ucar Emel , Odabas Mehtap , Kaya Nur Unal , Sadioglu Rezzan Eren , Celik Gulden , Acikgoz Elif , Sayarlioglu Hayriye , Turkmen Ercan , Delibalta Bulbul , Aktas Nimet , Cakir Selma Kuran , Kaya Emel Acar , Alsancak Serap , Ayar Yavuz , Ustunel Narin , Inan Zuhal , Yildirim Tolga , Sen Fatma , Oruc Aysegul , Korkmaz Rahime , Kayadibi Huseyin , Ates Kenan
Published: November 2023

Introduction

We aimed to evaluate the relationship between the hand fine motor skills of peritoneal dialysis (PD) practitioners and PD‐related peritonitis.

Methods

This multicenter prospective observational study was conducted with 120 incident PD patients. Patients were divided into two groups who had PD‐related peritonitis within the first year as Group 1, and those who did not as Group 2. Hand fine motor skills were evaluated by Nine‐Hole Peg Test (NHPT) and Nut Screwing Test (NST).

Results

Initial NHPT (28.5 ± 6.0 s vs. 25.8 ± 5.0 s, p = 0.011) and NST (82.3 (61.5–102.8) s versus 65.3 (52.3–88.5) s p = 0.023) scores were significantly higher in Group 1 than Group 2. In multivariate logistic regression analysis, NHPT, Body Mass Index, Mini‐Mental Test, self PD practitioner, and catheter complications were found to be independent variables in predicting PD‐related peritonitis.

Conclusion

Decreased hand fine motor skills of PD patients is a risk factor for peritonitis.