bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Early Pulmonary Senescence in Experimental Sepsis
Authors: Mösenlechner Martin , Schlösser Daniela , Braumüller Sonja , Dörfer Lena , Mannes Marco , Kawach Rawan , Strauss Gudrun , Schmidt Christoph Q. , Lupu Ludmila , Huber-Lang Markus S. 
Published: December 2024

Abstract

Background: Sepsis continues to pose a significant threat to human life and represents a substantial financial burden. In addition to replicative stress resulting from telomeric loss, recent studies have identified multiple factors contributing to cell cycle arrest. Furthermore, our understanding of pathways associated with cellular senescence, such as CD47-mediated suppression of efferocytosis, has expanded. However, beyond in vitro experiments, the impact of cell stress during complex systemic illnesses, including sepsis, remains poorly understood. Consequently, we conducted an investigation into molecular alterations related to senescence-associated pulmonary mechanisms during experimental non-pulmonary sepsis.

Methods: Male C57BL/6JRj mice were anesthetized and subjected to either control conditions (sham) or cecal ligation and puncture (CLP) to induce sepsis. 24 h or 7 d after CLP, animals were sacrificed and blood, bronchoalveolar fluids and lungs were harvested and analyzed for morphological and biochemical changes.

Results: Histological damage in pulmonary tissue, as well as increases in plasma levels of surfactant protein D, indicated development of alveolar-focused acute lung injury after CLP. Additionally, we observed a significant upregulation of the CD47-QPCTL-SHP-1-axis in lungs of septic mice. Whereas the expression of p16, a marker primarily indicating manifested forms of senescence, was decreased after CLP, the early marker of cellular senescence, p21, was increased in the lungs during sepsis. Later, at 7 d after CLP, pulmonary expression of CD47 and QPCTL-1 was decreased, whereas SHP-1 was significantly enhanced.

Conclusion: Our findings suggest an activation of senescent-associated pathways during experimental sepsis. However, expanding the experiments to other organ systems and in vivo long-term models are necessary to further evaluate the sustained mechanisms and immunopathophysiological consequences of cellular senescence triggered by septic organ injury.
Towards Non-Invasive White Blood Cell Count in Humans
Authors: Bagramyan Arutyun , Wu Juwell W. , Mirsanaye Kamdin , Alt Clemens , Lin Charles P. 
Published: November 2024

AbstractDespite rapid advances in diagnostic and imaging technologies, a method for noninvasive monitoring of the immune system does not exist. The standard white blood cell count (WBCC), a key clinical measure for assessing patients’ health, requires drawing blood, which poses inherent risks for secondary infection and anemia in vulnerable patient populations. In addition, the specialized equipment, expertise, and infrastructure are not always available in resource-poor settings. Here we present a method for noninvasive and label-free WBCC by imaging human oral mucosa with a miniaturized oblique back-illumination microscope (mOBM). In a pilot study involving 34 healthy subjects, we validated our system’s ability to detect and quantify circulating leukocytes and compared our image-based WBCC to standard laboratory measurements. The ability to perform noninvasive WBCC will enable real-time assessment of the immune status during infection and inflammation or in response to therapeutic intervention without repetitive blood sampling.
Online prediction of optimal deep brain stimulation contacts from local field potentials in chronically-implanted patients with Parkinson’s disease
Authors: Muller Marjolein , Scafa Stefano , Hanafi Ibrahem , Varescon Camille , Palmisano Chiara , van der Gaag Saskia , Zutt Rodi , van der Gaag Niels A , Hoffmann Carel F.E. , Bloch Jocelyne , Jiménez Mayte Castro , Bally Julien F. , Capetian Philipp , Isaias Ioannis U. , Moraud Eduardo M. , Contarino M. Fiorella 
Published: November 2024

AbstractBackgroundThe selection of optimal contacts for chronic deep brain stimulation (DBS) requires manual iterative testing of multiple stimulation configurations: the monopolar review. This requires time, highly trained personnel, and can cause patient discomfort. The use of neural biomarkers may help speed up this process.ObjectiveThis study aimed to validate the use of local field potentials (LFP) from a chronically implanted DBS neurostimulator to inform clinical selection of optimal stimulation contact-levels.MethodsWe retrospectively analysed bipolar LFP-recordings performed in patients with Parkinson’s disease OFF-medication and OFF-stimulation across three centres. For each contact-level chosen clinically, we ranked the recordings obtained by different channels according to the informative value of various beta-band (13-35Hz) power measures. We then developed two prediction algorithms: (i) a “decision-tree” method for direct, in-clinic use, and (ii) a “pattern based” method for offline validation. We finally compared these approaches to existing prediction algorithms.ResultsWe included 68 subthalamic nuclei from the Netherlands (NL), 21 from Switzerland (CH), and 32 from Germany (DE). Recording channel rankings depended on the clinically chosen contact-level. When predicting the first two contact-levels, the online “decision tree” method achieved a predictive accuracy of 86.5% (NL), 86.7% (CH), and 75.0% (DE), respectively. The offline “pattern based” technique attained similar results. Both prediction techniques outperformed an existing algorithm and were robust in different clinical and recording conditions.ConclusionThis study demonstrates that using these new methods, LFP-signals recorded in-clinic can support the selection of stimulation contact-levels, with high accuracy, reducing DBS programming time by half.
Single cell RNA-sequencing reveals no evidence for meiotic sex chromosome inactivation in the threespine stickleback fish
Authors: Shaw Daniel E. , Ross Wynter D. , Lambert Alexis V. , White Michael A. 
Published: November 2024

AbstractSex chromosomes often evolve unique patterns of gene expression in spermatogenesis. In many species, sex-linked genes are downregulated during meiosis in response to asynapsis of the heterogametic sex chromosome pair (meiotic sex chromosome inactivation; MSCI). Our understanding of this process has been limited to a handful of species, including mammals,Drosophila, andC. elegans.Based on findings from these taxa, MSCI has been viewed as likely a conserved process. However, in other groups like teleost fish, our understanding of this process is limited. Teleost fish are a noteworthy group to investigate because sex chromosomes can rapidly evolve between closely related species. Transcriptional profiling of spermatogenesis at the single-cell level is a useful approach to investigate whether MSCI occurs in other species with independently derived sex chromosomes. Here, we investigate whether MSCI occurs in the threespine stickleback fish (Gasterosteus aculeatus), which have an X and Y chromosome that evolved less than 26 million years ago. Using single-cell RNA-seq, we found that the X and Y chromosomes do not have a signature of MSCI, maintaining gene expression across meiosis. Using immunofluorescence, we also show the threespine stickleback do not form a condensed sex body around the X and Y, a conserved feature of MSCI in many species. We did not see patterns of gene content evolution documented in other species with MSCI. Y-linked ampliconic gene families were expressed across multiple stages of spermatogenesis, rather than being restricted to post-meiotic stages, like in mammals. Our work shows MSCI does not occur in the threespine stickleback fish and has not shaped the evolution of the Y chromosome. In addition, the absence of MSCI in the threespine stickleback suggests this process may not be a conserved feature of teleost fish and argues for additional investigation in other species.Author SummaryAs male germ cells enter meiosis, the X and Y chromosome of many species undergo a drastic repression of gene expression. In mammals, this process has been shown to be essential for fertility, and the expression of sex-linked genes can lead to meiotic arrest and cell death. This process has only been studied in a handful of organisms, which limits our understanding how conserved MSCI is across the tree of life. Teleost fish are an understudied group with many examples of independently derived sex chromosomes across closely related species. Here, we investigate whether MSCI occurs in the threespine stickleback fish, using single-cell transcriptional profiling. We found gene expression remains active throughout meiosis on the sex chromosomes, indicating MSCI does not occur. This indicates that MSCI is not a conserved feature of all taxa and is not an inevitable outcome of degenerating Y chromosomes.
Aspirin reduces the mortality risk of Acute Respiratory Failure: an observational study using the MIMIC IV database
Authors: Jiang Zhenhong , Lv Shijin , Zhang Guohu , Fu Zengyan 
Published: November 2024

AbstractBackgroundAcute Respiratory Failure (ARF) is a serious complication of various diseases, characterized by a high mortality rate. Aspirin influences cyclooxygenase, which have a crucial role in inflammation, blood clotting, and immune system modulation. ARF is characterized by an uncontrolled inflammatory and pro-coagulant response, but aspirin can mitigate this inflammatory response by inhibiting platelet function, potentially leading to improved outcomes.Numerous studies have produced conflicting data concerning the impact of aspirin on individuals suffering from Acute Respiratory Failure. We performed an analysis of the MIMIC IV database to explore the association between aspirin use and the outcomes in ARF patients, as well as to ascertain the optimal dosing regimen for aspirin treatment.Materials and methodsARF patients’ clinical data were extracted from MIMICIV2.2. Propensity score matching was utilized to ensure comparability of baseline characteristics between the group receiving aspirin and the group not receiving aspirin. Subsequently, the link between aspirin and patient death was examined through the application of Kaplan-Meier estimations and Cox proportional hazard regression analyses.ResultsWe identified a cohort of 6,663 individuals suffering from ARF from the MIMIC IV database.Following propensity score matching in a sample of 4,008 participants, multivariate Cox proportional hazards analysis revealed a lower hazard of dying within 90 days for those in the aspirin group versus the non-users group (adjusted Hazard Ratio: 0.723; 95% Confidence Interval: 0.652 to 0.802). Additionally, the Kaplan-Meier survival curves indicated that the 90-day survival rate was higher among aspirin users compared to non-users (log-rank test p< 0.001). And the median duration of survival for patients undergoing aspirin therapy was considerably extended compared to those who did not receive it, amounting to 15.60 days versus 10.36 days, respectively In the aspirin group, the median ICU stay length was longer than non-users group (6.93 days vs. 6.08 days, p <0.001).Patients in the aspirin use group had a significantly shorter duration of mechanical ventilation compared to those in the non-aspirin use group(54.95 days vs. 58.00 days, p <0.001).ConclusionAspirin may reduce the 30-day or 90-day mortality risk in ARF patients and also shorten the duration of mechanical ventilation. Aspirin could be an effective medication in the treatment of ARF patients.
Vertical transmission of Dengue virus type-3 and metagenomic virome profiles ofAedes aegyptimosquitoes collected in Kisumu, Kenya
Authors: Wanjiru Tabitha , Bulimo Wallace , Langat Solomon , Kinyua Johnson , Odemba Nicholas , Yalwala Santos , Oullo David , Ochieng Richard , Ngere Francis , Kerich Gladys , Ambale Janet , Achieng Eunice , Abuom David , Egbo Timothy , Johnson Jaree , Ojwang Elly , Eads John , Garges Eric , Eyase Fredrick 
Published: November 2024

ABSTRACTAedes aegyptiis the main vector of several arboviruses including chikungunya, dengue, yellow fever and Zika. Beyond arboviruses,Aedes aegyptiharbours insect-specific viruses (ISVs), which can modulate mosquito’s ability to transmit diseases by interfering with viral processes and triggering immune responses. Both arboviruses and ISVs can be transmitted vertically, where viruses are passed from parent to offspring. The lack of systematic molecular and entomological surveillance, has left the diversity of viruses in localAedes aegyptipopulations largely unexplored. This study aimed to characterize the viromes ofAedes aegyptimosquitoes from Kisumu, Kenya, focusing on viral diversity. Immature larvae and pupae were collected from Jua Kali area in Kisumu, reared into adults, and subjected to viral isolation by cell culture and metagenomic next-generation sequencing. RNA extraction, library preparation, and Illumina MiSeq sequencing were performed on CPE positive pools and metagenomic superpools. Initial data analysis was conducted using the CZ-ID platform, with quality control applied using PrinseqLite v0.20.4 to filter low-quality reads and remove adapters. De novo sequence assembly was performed with MEGAHIT v1.2.9, followed by BLAST analysis. Phylogenetic relationships were analyzed using the Maximum Likelihood method. A total of 2,142 femaleAedes aegypti, grouped into 86 pools and 4 superpools, were processed for cell culture and metagenomic next-generation sequencing respectively. Dengue virus type-3 was detected in one of the 86 pool. Additionally, a variety of ISVs were identified, including Iflaviruses related to Tesano Aedes Iflavirus (TeAV), Armigeres Iflavirus, and Negeviruses related to Rabai Virus. An unclassified virus closely related to Korle-Bu Aedes virus was also detected. Our study provides insights into the viral diversity withinAedes aegyptimosquitoes in Kisumu and evidence of natural vertical transmission, specifically transovarial transmission of dengue virus type-3. Ongoing research is imperative to unravel vertical transmission mechanisms and subtleties governing ISV-arbovirus interactions across diverse environmental settings.
Enhanced SNP Genotyping with Symmetric Multinomial Logistic Regression
Authors: Nielsen Malte B. , Eriksen Poul S. , Mogensen Helle S. , Morling Niels , Andersen Mikkel M. 
Published: November 2024

AbstractIn genotyping, determining Single Nucleotide Polymorphisms (SNPs) is standard practice, but it becomes difficult when analysing small quantities of input DNA, as is often required in forensic applications. Existing SNP genotyping methods, such as the HID SNP Genotyper Plugin (HSG) from Thermo Fisher Scientific, perform well with adequate DNA input levels but often produce erroneously called genotypes when DNA quantities are low. To mitigate these errors, genotype quality can be checked with the HSG. However, enforcing the HSG’s quality checks decreases the call rate by introducing more no-calls, and it does not eliminate all wrong calls. This study presents and validates a Symmetric Multinomial Logistic Regression (SMLR) model designed to enhance genotyping accuracy and call rate with small amounts of DNA. Comprehensive bootstrap and cross-validation analyses across a wide range of DNA quantities demonstrate the robustness and efficiency of the SMLR model in maintaining high call rates without compromising accuracy compared to the HSG. For DNA amounts as low as 31.25 pg, the SMLR method reduced the rate of no-calls by 50.0% relative to the HSG while maintaining the same rate of wrong calls, resulting in a call rate of 96.0%. Similarly, SMLR reduced the rate of wrong calls by 55.6% while maintaining the same call rate, achieving an accuracy of 99.775%. The no-call and wrong-call rates were significantly reduced at 62.5–250 pg DNA. The results highlight the SMLR model’s utility in optimising SNP genotyping at suboptimal DNA concentrations, making it a valuable tool for forensic applications where sample quantity and quality may be decreased. This work reinforces the feasibility of statistical approaches in forensic genotyping and provides a framework for implementing the SMLR method in practical forensic settings. The SMLR model applies for genotyping biallelic data with a signal (e.g. reads, counts, or intensity) for each allele. The model can also improve the allele balance quality check.
Enhancing Detection of Polygenic Adaptation: A Comparative Study of Machine Learning and Statistical Approaches Using Simulated Evolve-and-Resequence Data
Authors: Caliendo Cosima , Gerber Susanne , Pfenninger Markus 
Published: November 2024

AbstractDetecting signals of polygenic adaptation remains a significant challenge in evolutionary biology, as traditional methods often struggle to identify the associated subtle, multi-locus allele-frequency shifts. Here, we introduced and tested several novel approaches combining machine learning techniques with traditional statistical tests to detect polygenic adaptation patterns. We implemented a Naive Bayesian Classifier (NBC) and One-Class Support Vector Machines (OCSVM), and compared their performance against the Fisher’s Exact Test (FET). Furthermore, we combined machine learning and statistical models (OCSVM-FET and NBC-FET), resulting in 5 competing approaches. Using a simulated data set based on empirical evolve-and-resequencingChironomus ripariusgenomic data, we evaluated methods across evolutionary scenarios, varying in generations and numbers of loci under selection. Our results demonstrate that the combined OCSVM-FET approach consistently outperformed competing methods, achieving the lowest false positive rate, highest area under the curve, and high accuracy. The performance peak aligned with the late dynamic phase of adaptation, highlighting the method’s sensitivity to ongoing selective processes and thus for experimental approaches. Furthermore, we emphasize the critical role of parameter tuning, balancing biological assumptions with methodological rigor. Our approach thus offers a powerful tool for detecting polygenic adaptation in pool sequencing data particularly from evolve-and-resequence experiments.Author’s SummaryOrganisms often adapt to environmental changes through polygenic adaptation - a process where multiple genes collectively contribute to evolutionary change. However, detecting these small shifts spread across multiple genes has been a persistent challenge for researchers. We developed new computational methods that combine machine learning with traditional statistical approaches to better detect these subtle genetic changes. Using data from a laboratory evolution experiment with the freshwater midgeChironomus riparius, we tested five different approaches to identify genes under selection. Our results showed that combining the machine learning technique One Class Support Vector Machines with a traditional statistical test (Fisher’s Exact Test) was particularly effective at identifying genes involved in adaptation. This combined approach excelled specifically in detecting ongoing adaptive changes while avoiding false positives. Our method provides a reliable tool for researchers studying evolutionary adaptation, particularly in laboratory evolution experiments where populations are tracked over multiple generations. This advancement facilitates improved understanding of how organisms adapt to new environments, which is increasingly important in the context of rapid environmental changes.
Assessing the impact of temperament on training efficiency inex-situRed Brocket Deer (Mazama americana)
Authors: Gragnanello Lara Caveanha , Cerezo Mariana Parra , Pizzutto Cristiane Schilbach , Paranhos da Costa Mateus José Rodrigues 
Published: November 2024

AbstractThe personality of wild animals has been extensively discussed due to its significant influence onex-situmanagement and conservation methods. However, there is still limited research directly addressing its impact on habituation and conditioning processes, which are essential techniques in conservation centers, zoos, and research institutions. This study aimed to demonstrate how individual personality variation affects training. We conducted the research at the Deer Research and Conservation Center of the Faculty of Agricultural and Veterinary Sciences, São Paulo State University, in Jaboticabal-SP, Brazil, with twelve red brocket deer (Mazama americana). Temperament tests were performed at the beginning of the study, assessing the animals’ reactivity to the presence of an unfamiliar human and during handling procedures. Following these tests, we initiated the processes of habituation and training of the animals. Three deer did not habituate to the trainer’s presence, being not subjected to operant conditioning; and four did it in just seven sessions. Among the nine deer that participated in the conditioning process, only five learned all the commands, representing a success rate of 41.66%. We concluded that more reactive animals, characterized as nervous and agitated, exhibited poorer performance in training. In contrast, less reactive animals, which were calmer and either allowed to approach or approached voluntarily an unfamiliar person, learned the commands more effectively.
Characterizing neuronal and population responses to electrical stimulation in the human hippocampo-cortical network
Authors: van der Plas Mircea , Roux Frederic , Chelvarajah Ramesh , Sawlani Vijay , Staresina Bernhard , Wimber Maria , Rollings David T. , Hanslmayr Simon 
Published: November 2024

AbstractDirect electrical stimulation (DES) can advance our understanding of the intricate dynamics of the human hippocampo-neocortical network, which underlies complex cognitive processes such as spatial cognition and memory. This knowledge can help Neurotechnology to more effectively interface with this network and improve its functions. Here, we investigated the effects of DES in seven epilepsy patients under medical supervision recording single neuron activity alongside local field potentials to investigate neural responses to single pulses at different levels of granularity. Our results demonstrate that (i) single neurons respond to local electrical stimulation with a stereotypical pattern of short-lived increased excitation, followed by sustained inhibition, (ii) that input into the hippocampus from neocortex takes ∼100 ms, and (iii) that output from the hippocampus to the neocortex is gated by theta phase. These results are vital to inform the optimal choice of parameters for future electrical stimulation studies targeting the human memory system.