bluuebunny/crossref_metadata_2025_split huggingface dataset:
Length of ischemic time is critical for accurate determination of homologous recombination capacity by immunostaining in FFPE tumor samples
Authors: Karagöz Ezgi , Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Salko Matilda , Härkönen Anni , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Kauppi Liisa 
Published: November 2024

AbstractHomologous recombination-deficient (HRD) high-grade serous ovarian cancers (HGSC) are more sensitive to PARP inhibitors compared to their homologous recombination-proficient counterparts. To match the right drug with the right patient the HRD status must be accurately determined. Functional HRD assays, which assess HRD status by quantifying RAD51, a key homologous recombination (HR) protein, are a promising approach for identifying HRD cases. However, these tests are yet to be optimized for pre-analytical variables, specifically HGSC tissue sampling protocols, which can impact RAD51 signal measurement. In this study, we systematically analyzed the impact of ischemic time on formalin-fixed paraffin-embedded HGSC specimens. We demonstrate that the maximum length of ischemic time compatible with accurate HRD calls is 2 hours post-excision. Our findings highlight the importance of properly monitoring and recording sample handling processes, particularly in HGSC, and warrant caution when using archival tumor material where this information is unavailable. Non-optimal pre-analytical factors like ischemic time can cause false HRD calls, thus leading to incorrect patient stratification, which may result in the initiation of treatments with potential side effects without a therapeutic benefit.
Open Source, Open Science: Development of OpenLESS as the Automated Landing Error Scoring System
Authors: Turner Jeffrey A. , Reiche Elaine T. , Hartshorne Matthew T. , Lee Connor C. , Blodgett Joanna M. , Padua Darin A. 
Published: November 2024

ContextThe Open Landing Error Scoring System (OpenLESS) is a novel development aimed at automating the LESS for assessment of lower extremity movement quality during a jump-landing task. With increasing utilization of clinical measures to monitor outcomes and limited time during clinical visits for a lengthy analysis of functional movement, there is a pressing need to extend automation efforts. Addressing these issues, OpenLESS is an open-source tool that utilizes a freely available markerless motion capture system to automate the LESS using three-dimensional kinematics.ObjectiveTo describe the development of OpenLESS, examine the validity against expert rater LESS scores in healthy and clinically relevant cohorts, and assess the intersession reliability collected across four time points in an athlete cohort.DesignObservationalParticipants92 participants (72 females and 20 males, mean age 23.3 years) from healthy, post-anterior cruciate ligament reconstruction (ACLR; median 33 months since surgery), and amateur athlete cohorts.Main Outcome Measure(s)A software package, “OpenLESS,” was developed to interpret movement quality (LESS score) from kinematics captured from markerless motion capture. Validity and reliability were assessed with intraclass correlation coefficients (ICC), standard error of measure (SEM), and minimal detectable change (MDC).ResultsOpenLESS agreed well with expert rater LESS scores for healthy (ICC2,k=0.79) and clinically relevant, post-ACLR cohorts (ICC2,k=0.88). The automated OpenLESS system reduced scoring time, processing all 159 trials in under 15 minutes compared to the 18.5 hours (7 minutes per trial) required for manual expert rater scoring. When tested outside laboratory conditions, OpenLESS showed excellent reliability across repeated sessions (ICC2,k>0.89), with a SEM of 0.98 errors and MDC of 2.72 errors.ConclusionOpenLESS shows promise as an efficient, automated tool for clinically assessing jump-landing quality, with good validity versus experts in healthy and post-ACLR populations, and excellent field reliability, addressing the need for objective movement analysis.KEY POINTSOpenLESS accurately detected jump-landing events (ICC>0.99) using markerless motion capture, validating its use as an alternative to laboratory-based force plate measurements.The automated scoring system showed good agreement with expert raters in healthy (ICC=0.79) and post-ACLR (ICC=0.88) populations.OpenLESS demonstrated good to excellent test-retest reliability (ICC=0.89) across multiple testing sessions, with minimal score variation, supporting its utility for longitudinal movement assessment.
The adaptation of chlamydiae to facultative host multicellularity
Authors: Helmlinger Lukas , Arthofer Patrick , Cyran Norbert , Collingro Astrid , Horn Matthias 
Published: November 2024

SummaryThe phylum Chlamydiota consists of obligate intracellular bacteria comprising the human pathogenChlamydia trachomatisand a large variety of species infecting animals and protists. Despite their enormous diversity, a feature shared by all known chlamydiae is their biphasic developmental cycle, consisting of intra- and extracellular stages with substantial differences in morphology and physiology. A similarly remarkable shift occurs in the amoebaDictyostelium discoideumand related dictyostelids in their so-called social life cycle, leading to the formation of spores through aggregation of vegetative trophozoites and the development of multicellular fruiting bodies. Although dictyostelids undergo symbioses with various bacteria, chlamydiae have only recently been found to be associated with this host. Here we report the isolation of aDictyostelium giganteumstrain naturally infected with a chlamydial symbiont, identified as a novel species,Reclusachlamydia socialis. The symbiont is retained in all stages of the host’s social life cycle and notably lacks an extracellular form. Combining fluorescence microscopy and quantitative PCR we showed that transmission is entirely dependent on cell-to-cell contact during the host aggregation stage. The absence of an extracellular stage is further supported by transmission electron microscopy and the lack of genes essential for chlamydial developmental cycle regulation and extracellular survival. This unprecedented variation of a highly conserved developmental feature that evolved more than a billion years ago illustrates the remarkable adaptability of chlamydiae. This study adds to our understanding of endosymbiosis in the face of facultative multicellularity.
Decoupling of GABA and Glutamine-Glutamate Dynamics and their role in tactile perception: An fMRS Study
Authors: Pasanta Duanghathai , Powell Helen , Hafeez Nauman , Lythgoe David J , Puts Nicolaas A 
Published: November 2024

AbstractTactile processing is fundamental for our daily lives. In particular, adaptation, the mechanism by which neural (and behavioural) responses change due to repeated stimulation, is key in adjusting our responses to the environment and is often affected in neurodevelopmental conditions such as autism and ADHD. While GABA and glutamate—the main inhibitory and excitatory neurotransmitters— are known to be fundamental for encoding sensory input, we know little regarding the dynamic responses of the GABA and glutamatergic systems during tactile processing. Here, we examine how GABA and glutamine+glutamate (Glx)in vivodynamics change during repetitive tactile stimulation and how these changes relate to tactile perception in a healthy population, using functional magnetic resonance spectroscopy (fMRS). Our study showed that repetitive tactile stimulation induced a decoupling between GABA and Glx during the first stimulation blocks as suggested by a negative correlation between GABA and Glx, which changed from a positive correlation at baseline. Subsequently, a multivariate time series analysis showed a predictive temporal relationship between Glx and GABA, showing that changes in these metabolites are temporally linked with an estimated lag of 6 seconds informing on a complex metabolite response function. The absence of gross metabolite change suggests that Glx and GABA adjust in relation to each other in response to repeated tactile stimulation. Furthermore, individual differences in the changed GABA and Glx levels correlated with perceptual measures of touch. Together, our study highlights the complex relationship between GABA and glutamate in tactile processing and demonstrates that experience-dependence plasticity induces a decoupling between these key metabolites. Further study into their dynamic interplay may be key to understanding adaptation as meso-levels in the brain and how these mechanisms differ in neurodevelopmental and neurological conditions.
Discovery of alternative stable states in a synthetic human gut microbial community
Authors: Garza Daniel , Liu Bin , Velde Charlotte van de , Saha Pallabita , Zhou Xingjian , Gonze Didier , Simoens Kenneth , Bernaerts Kristel , Faust Karoline 
Published: November 2024

AbstractSeveral human-associated microbial communities exist in multiple configurations and can change their composition in response to perturbations, remaining in an altered state even after the perturbation ends. Multistability has been previously proposed to explain this behavior for gut microbiota in particular, but has not been clearly demonstrated experimentally. Here, we first investigated the life history strategies of three common human gut bacteria to identify mechanisms driving alternative states. We then used this data to build and parameterize a kinetic model, which predicted that alternative states emerge due to phenotype switching between subpopulations of the same species. Perturbation experiments supported these predictions, and confirmed the existence of alternative states. Finally, simulations showed that phenotype switching can also explain alternative states in larger communities. Thus, a transient perturbation combined with metabolic flexibility is sufficient for alternative communities to emerge, implying that they are not necessarily explained by differences between individuals.One-Sentence SummaryWe demonstrate the existence of alternative states in a human gut microbial community and propose phenotype switching as a mechanism explaining their emergence.
Structural basis for phosphatidylcholine synthesis by bacterial phospholipidN-methyltransferases
Authors: Watanabe Yasunori , Kumeta Hiroyuki , Watanabe Seiya 
Published: November 2024

AbstractIn phosphatidylcholine (PC)-containing bacteria, PC is synthesized by phospholipidN-methyltransferases (Pmts) and plays an important role in the interactions between symbiotic and pathogenic bacteria and their eukaryotic host cells. Pmts catalyze the SAM dependent three methylation reactions of the head group of phosphatidylethanolamine (PE) to form PC through monomethyl PE and dimethyl PE. However, the precise molecular mechanisms underlying PC biosynthesis by PmtA remain largely unclear, owing to the lack of structural information. Here, we determined the crystal structures ofAgrobacterium tumefaciensPmt (AtPmtA) in complex with SAH or 5′-methylthioadenosine. Crystal structures and NMR analysis revealed the binding mode of AtPmtA to SAH in solution. Structure-based mutational analyses showed that a conserved tyrosine residue in the substrate-binding groove is involved in methylation. Furthermore, we showed that differences in substrate specificity among Pmt homologs were determined by whether the amino acid residues comprising the substrate-binding groove were isoleucine or phenylalanine. These findings provide a structural basis for understanding the mechanisms underlying Pmts-mediated PC biosynthesis.
Spatial Flux Balance Analysis reveals tissue-of-origin and spatially dependent metabolic rewiring in renal and colorectal cancer
Authors: Maspero Davide , Marteletto Giovanni , Lapi Francesco , Galuzzi Bruno G. , Ruano Irene , Vandenbosch Ben , Yin Ke , Tejpar Sabine , Graudenzi Alex , Heyn Holger , Pascual-Reguant Anna , Damiani Chiara 
Published: November 2024

1AbstractSpatial metabolomics holds great promise for unraveling the complexities of metabolic reprogramming in cancer, yet its development lags behind the rapid progress of spatial transcriptomics (ST). To bridge this gap and maximize the value of spatial gene expression datasets, we present Spatial Flux Balance Analysis (spFBA), a novel framework that transcends the limitations of existing gene set enrichment methods. The spFBA approach builds upon previous work designed for bulk and single-cell data to return Flux Enrichment Scores, up to the level of single reactions, that can distinguish their preferred directional usage retaining spatial resolution. spFBA integrates differential constraints on flux boundaries in steady-state metabolic modeling, informed by spatial gene expression, and utilizes corner-based flux sampling.We first tuned and validated spFBA using a publicly available 10x Visium ST dataset from renal cancer samples at the tumor-normal tissue interface. spFBA demonstrated the ability to recapitulate the tissue architecture in renal tumor sections, clearly delineating sustained metabolic growth in the tumor core compared to adjacent normal renal parenchyma. Furthermore, spFBA captured the Warburg effect, revealing distinct metabolic subpopulations within the tumor core, while highlighting lactate excretion as a hallmark across all subpopulations. We then applied spFBA to our own high-resolution ST datasets generated with stereo-seq from a colon cancer patient, including both primary tumor and liver metastases. Unlike the renal case, spFBA uncovered extensive areas of tumor cells consuming lactate in both primary and metastatic sites, with stromal regions in liver metastases producing lactate, suggesting a reverse Warburg effect at play.These findings highlight that cancer metabolic rewiring and the tumor composition of metabolic subpopulations depend highly on the tissue of origin and the spatial context within the target organ. spFBA emerges as a powerful tool to leverage the rapidly growing collection of spatial gene expression data, offering unprecedented insights into the intricate metabolic landscape of cancer.
Smart 3D super-resolution microscopy reveals the architecture of the RNA scaffold in a nuclear body
Authors: Berrevoets Enya S. , Kessler Laurell F. , Balakrishnan Ashwin , Müller-McNicoll Michaela , Rieger Bernd , Stallinga Sjoerd , Heilemann Mike 
Published: November 2024

AbstractSmall subcellular organelles orchestrate key cellular functions. How biomolecules are spatially organized within these assemblies is poorly understood. Here, we report an automated super- resolution imaging and analysis workflow that integrates confocal microscopy, morphological object screening, targeted 3D super-resolution STED microscopy and quantitative image analysis. Using this smart microscopy workflow, we targeted the 3D organization of an architectural RNA that constitutes the structural backbone of paraspeckles, a membraneless nuclear organelle. Using site-specific labeling, morphological sorting and particle averaging, we reconstructed the morphological space of paraspeckles along their development cycle from over 10,000 individual particles. Applying spherical harmonics analysis, we report so-far unknown heterotypes of RNA organization. By integrating multi- positional labeling, we determined the coarse conformation of the RNA within the organelle and found the 3’ end forming a loop-like structure at the surface of the paraspeckle. Our study reveals key structural features of nuclear paraspeckle structure and growth, as well as on the molecular organization of the scaffold RNA.
Trade-off between sample volume passaged and number of passages during serial dilution for bacterial enumeration
Authors: Jain Monika , Begum Shuhada , Bhuyan Shuvam , Nath Chayanika , Kashyap Uchakankhi , Dutta Lukapriya , Giri Shubhra Jyoti , Deka Nishita , Mandal Manabendra , Kumar Aditya , Ray Suvendra Kumar 
Published: November 2024

AbstractAccurate enumeration of bacteria in a culture is the first step in both fundamental as well as applied research in microbiology. Serial dilution is an age old method used widely by researchers for enumerating viable bacteria in a culture where a specific sample volume is passaged successively to a specific diluent volume. Here, we demonstrated that a higher sample volume is a better representation of bacterial population than a lower sample volume, which was in concordance with the random nature of bacterial distribution in culture. Therefore, a bigger sample to diluent ratio during serial dilution appears more favorable for an accurate bacterial enumeration than a smaller ratio. But surprisingly, enumeration using the different dilution ratios such as 1:9, 1:99 and 1:999 in 1.0 mL final volume yielded similar results with the exception of 1:999, where 1 μL sample was passaged. However, in 10.0 mL final volume of dilution, the above three dilution ratios exhibited similar bacterial enumeration. The experiment was performed using two different bacterial cultures such asEscherichia coliandRalstonia pseudosolanacearum. Our results indicated that the advantage gained due to lesser number of passages in case of a lower sample volume could overcome the disadvantage associated with it, thereby co-aligning the different dilution ratios with regards to enumeration. Hence, although in laboratory, 1:9 dilution ratio is usually performed during serial dilution, our results suggest that dilution ratios such as 1:99 in 1 mL dilution volume and ratios such as 1:99 and 1:999 in 10 mL dilution volume are equally effective, which also reduces time, cost and labor.
Head-to-head comparison of the RMI and ADNEX models to estimate the risk of ovarian malignancy: systematic review and meta-analysis of external validation studies
Authors: Barreñada Lasai , Ledger Ashleigh , Kotlarz Agnieszka , Dhiman Paula , Collins Gary S. , Wynants Laure , Verbakel Jan Y. , Valentin Lil , Timmerman Dirk , Van Calster Ben 
Published: November 2024

AbstractBackgroundADNEX and RMI are models to estimate the risk of malignancy of ovarian masses based on clinical and ultrasound information. The aim of this systematic review and meta-analysis is to synthesise head to-head comparisons of these models.MethodsWe performed a systematic literature search up to 31/07/2024. We included all external validation studies of the performance of ADNEX and RMI on the same data. We did a random effects meta-analysis of the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, net benefit and relative utility at 10% malignancy risk threshold for ADNEX and 200 cutoff for RMI.ResultsWe included 11 studies comprising 8271 tumours. Most studies were at high risk of bias (incomplete reporting, poor methodology). For ADNEX with CA125 vs RMI, the summary AUC to distinguish benign from malignant tumours in operated patients was 0.92 (CI 0.90-0.94) for ADNEX and 0.85 (CI 0.80-0.89) for RMI. Sensitivity and specificity for ADNEX were 0.93 (0.90-0.96) and 0.77 (0.71-0.81). For RMI they were 0.61 (0.56-0.67) and 0.93 (0.90-0.95). The probability of ADNEX being clinically useful in operated patients was 96% vs 15% for RMI at the selected cutoffs (10%, 200).ConclusionADNEX is clinically more useful than RMI.Systematic review registrationCRD42023449454
An efficient spectral method for two-dimensional Benjamin–Bona–Mahony–Burgers equation
Authors: Jiao Yujian , Zhou Yu 
Published: November 2024

PurposeIn this paper, we propose an efficient spectral method for solving the two-dimensional Benjamin–Bona–Mahony–Burgers equation. The new basis functions align well with the problem, the discrete system is sparse and can be efficiently inverted, and the numerical solutions exhibit spectral accuracy in space.Design/methodology/approachTo efficiently simulate the two-dimensional Benjamin–Bona–Mahony–Burgers equation, we utilize transformed generalized Jacobi polynomials and construct the basis functions using the tensor product of these newly introduced polynomials. We provide relevant approximation results. Subsequently, we propose a spectral scheme for the underlying problem, and prove the well-posedness of the scheme, along with the boundedness and energy dissipation of the numerical solutions. We analyze the generalized stability and convergence of the numerical solution of the proposed scheme. Some numerical simulations are presented to demonstrate the efficacy of this newly proposed method.FindingsThe new basis functions generated by tensor product of the transformed Jacobi polynomial align well with the underlying problem and simplify the theoretical analysis. The spatial discrete system is sparse and can be efficiently inverted. The numerical solutions exhibit spectral accuracy in space.Originality/valueWe introduce transformed generalized Jacobi polynomials to construct basis functions and present relevant approximation results. We propose an efficient spectral scheme for the two-dimensional Benjamin–Bona–Mahony–Burgers equation, accompanied by optimal error analysis. This new approach achieves spectral accuracy. Moreover, the proposed method and the techniques developed in this work can be applied to simulate a wide range of other nonlinear problems.
SME rebalancing short-term and long-term debt ratios: the role of financial distress costs
Authors: Serrasqueiro Zélia , Sardo Filipe , Neves Elisabete , Morais Flávio 
Published: November 2024

Purpose
This study seeks to analyze the effect of the financial distress costs on small and medium-sized enterprises (SME) rebalancing of short-term and long-term debt ratios.

Design/methodology/approach
The authors use the system-generalized method of moments (GMM-sys) to treat data collected for a sample of Portuguese manufacturing SMEs for the period 2011–2017.

Findings
Financial distress costs positively impact the speed with which SMEs rebalance their short-term and long-term debt ratios The positive effect of financial distress costs on the speed of adjustment (SOA) is higher for the short-term than for the long-term debt ratio. This result suggests that SMEs seek to overcome quicker the financing imbalance in the short run, probably, due to their dependence on short-term debt.

Practical implications
SME owners-managers should seek to rely less on short-term debt to reduce the firm default risk, the financing imbalance and the financial distress costs. Banks should lend long-term loans to SMEs, given that the high financial distress risk of these firms results from their dependence on short-term debt financing. Policymakers should promote SME access to external finance sources with lower transaction costs, to SME rebalance their capital structures.

Originality/value
This study analyzes the effect of financial distress costs on the SOA with which SMEs rebalance their capital structure. We estimate the financial distress costs based on a hazard model, to analyze their effect on the SOA toward the target debt ratios.