bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early decreased respiratory chain capacity in resuscitated experimental sepsis is a major contributor to lactate production
Authors: von Seth Magnus , Hillered Lars , Otterbeck Alexander , Hanslin Katja , Larsson Anders , Sjölin Jan , Lipcsey Miklós 
Published: August 2023

Abstract

Background
Increased plasma lactate levels in patients with sepsis may be due to insufficient oxygen delivery, but mitochondrial dysfunction or accelerated glycolysis may also contribute. We studied the effect of the latter on muscle metabolism by using microdialysis in a sepsis model with sustained oxygen delivery and decreased energy consumption or mitochondrial blockade.

Methods
Pigs were subjected to continuous E. coli infusion (sepsis group, n = 12) or saline infusion (sham group, n = 4) for 3 hours (h). Protocolized interventions were applied to normalize the oxygen delivery and blood pressure. Microdialysis catheters were used to monitor muscle metabolism (naïve). The same catheters were used to block the electron transport chain with cyanide or the Na+/K+-ATPase inhibitor, ouabain locally.

Results
All pigs in the sepsis group had positive blood cultures and a Sequential Organ Failure Assessment (SOFA) score increase by at least 2, fulfilling the sepsis criteria. Plasma lactate was higher in the sepsis group than in the sham group (p < 0.001), whereas muscle glucose was lower in the sepsis group (p < 0.01). There were no changes in muscle lactate levels over time but lactate to pyruvate ratio (LPR) was elevated in the Sepsis vs. the Sham group (p < 0.05). Muscle lactate, LPR, and glutamate levels were higher in the sepsis group than in the sham group in the cyanide catheters (p < 0.001, all comparisons) and did not normalize in the former group.

Conclusions
In this experimental study on resuscitated sepsis, we observed increased aerobic metabolism and preserved mitochondrial function. Sepsis and electron transport chain inhibition led to increased LPR, suggesting a decreased mitochondrial reserve capacity in early sepsis.
Circ_0002131 contributes to LPS-induced apoptosis, inflammation and oxidative injury in HK-2 cells via inhibiting the binding between miR-942-5p and OXSR1
Authors: Zhang Pengjie , Yin Jian , Xun Liru , Ding Tong , Du Shuangkuan 
Published: August 2023

Abstract

Background
Circular RNAs (circRNAs) are implicated in the progression of sepsis-associated acute kidney injury (AKI). Circ_0002131 was shown to aggravate cell inflammation and oxidative stress in sepsis-induced AKI. The aim of this study was to investigate the role and underlying mechanism of circ_0002131 in sepsis-induced AKI.

Methods
Cell Counting Ki-8 assay was used for cell viability detection. Cell apoptosis was measured using flow cytometry. Circ_0002131, microRNA-942-5p (miR-942-5p) and oxidative stress responsive 1 (OXSR1) level analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. The protein levels were examined by western blot. Inflammatory factors were determined using Enzyme-linked immunosorbent assay. Oxidative injury was assessed via commercial kits. Target relation was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay.

Results
HK-2 cell viability was suppressed and apoptosis was enhanced by LPS. Circ_0002131 was highly expressed in LPS-treated HK-2 cells and sepsis-induced AKI patients. LPS-induced apoptosis, inflammation and oxidative injury of HK-2 cells were attenuated after silence of circ_0002131. Then, miR-942-5p was identified as a target for circ_0002131, and the regulation of circ_0002131 in LPS-induced cell injury was ascribed to reduce miR-942-5p level. Additionally, circ_0002131 targeted miR-942-5p to elevate OXSR1 expression. MiR-942-5p prevented LPS-evoked HK-2 cell injury via targeting OXSR1.

Conclusion
All results demonstrated that circ_0002131 promoted LPS-mediated HK-2 cell injury via miR-942-5p-mediated upregulation of OXSR1, suggesting that circ_0002131/miR-942-5p/OXSR1 axis was related to sepsis-induced AKI progression.
Yersinia pseudotuberculosis Bacteremia with Splenic Abscesses: A Case Report
Authors: Zewude Rahel Tefera , Stefanovic Aleksandra , Alem Zersenay 
Published: August 2023

Introduction:
Yersinia pseudotuberculosis has been known to cause a variety of clinical manifestations ranging from mild enteric illness to bacteremia with septic shock and extraintestinal abscesses. Patients with liver disease and iron overload are at risk of more severe disease manifestations.
Case Report:
A middle aged male with chronic alcohol use disorder presented with confusion and jaundice with ascites and asterixis noted on exam. His blood work was remarkable for neutrophilic leukocytosis, elevated liver enzymes and lactate. His abdominal CT revealed splenic microabscesses and a cirrhotic liver. Yersinia pseudotuberculosis was recovered from his blood cultures and he was treated with ceftriaxone following susceptibility results.
Conclusion:
Y. pseudotuberculosis should be considered in the differential diagnosis of splenic or other extraintestinal microabscesses particularly in patients with chronic liver disease.
Diagnostic performance of LumiraDx SARS-CoV-2 rapid antigen test compared to PCR for diagnosis of COVID-19 in Liberia
Authors: Badio Moses , Lindan Christina , Johnson Kumblytee , Reilly Cavan , Blie Julie , Shaw-Saliba Katy , Fayiah Tamba , McCullough John , Duworko J. Tanu , Higgs Elizabeth , Martin Jeffrey , Hensley Lisa 
Published: August 2023

AbstractBackgroundDiagnosis of SARS-CoV-2 infection in Liberia has primarily relied on polymerase chain reaction (PCR)-based testing at the country’s National Reference Laboratory. This centralized approach caused reporting delays, prompting evaluation of point-of-care antigen-based tests. We assessed the test performance of the LumiraDx™ SARS-CoV-2 Ag test (LumiraDx™, London, UK) in this setting.MethodsWe tested ambulatory individuals screened for enrollment into an observational cohort study of COVID-19 sequelae in Monrovia in 2021. We compared the results of LumiraDx testing of anterior nasal swab specimens to the results of PCR BioFire® R2.1P (bioMérieux, Salt Lake City, Utah) on eluent from nasopharyngeal swabs.ResultsWe evaluated 348 individuals. Among the 274 persons with symptoms, 49.3% were PCR-positive and 36.5% were antigen-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of LumiraDx in this group were 72.6% (95% CI: 64.3%-79.9%), 98.6% (95% CI: 94.9%-99.8%), 78.7% (CI: 71.9%-84.6%), and 98.0% (CI: 93.0%-99.8%), respectively. Among the 74 asymptomatic individuals, 12.2% were positive by PCR, and 5.5% by antigen testing, resulting in a sensitivity, specificity, NPV, and PPV of LumiraDx of 44.4% (95% CI: 13.7%-78.8%), 100% (95% CI: 94.5%-100%), 92.9% (CI: 84.1%-97.6%), and 100% (CI: 39.8%-100%), respectively.ConclusionAlthough the specificity and PPV of LumiraDx for diagnosing SARS-CoV-2 were high among persons with and without symptoms, the sensitivity was unacceptably low in both groups, and much less than that reported by the manufacturer. Before new point-of-care diagnostics are adopted, test performance needs to be assessed in the local setting.
DNA tetrahedron as a carrier of doxorubicin for metastatic breast cancer treatment
Authors: Vaswani Payal , Hema Naveena A , Kansara Krupa , Dahle Landon , Kumar Ashutosh , Bhatia Dhiraj 
Published: August 2023

AbstractMetastatic breast cancer is a significant clinical challenge calling for novel and efficient therapeutic approaches. DNA tetrahedron, a highly programmable nanocage, offers some promising attributes including biocompatibility, stability, and functionalization making it an attractive candidate for drug delivery. In this study, we have explored the potential of DNA tetrahedron as a carrier of doxorubicin, a DNA and RNA synthesis-inhibiting chemotherapy drug. We have encapsulated doxorubicin in DNA tetrahedron (TD: Dox) and subsequently focused on metastatic breast cancer cells for the effect of the same. We showed that TD: Dox has the potential to inhibit the migration of cancerous cells in the 2D model and inhibit the invasion of tumor cells in the 3D model as well. This system also can be uptaken inin vivozebrafish model as well. Overall, this study promises the TD: Dox system as an ideal drug delivery model and a viable approach for metastatic breast cancer treatment.
Evaluation of Loop-Mediated Isothermal Amplification (LAMP) for Rapid Detection ofCampylobacter jejuni
Authors: Caro-Castro Junior , Orellana-Peralta Fiorella , Flores-Leon Diana , Cuch-Meza Evans , Gavilán Ronnie G. , Quino Willi 
Published: August 2023

AbstractIn recent years, the worldwide incidence of diarrheal diseases caused byCampylobacter jejunihas been increasing, causing large-scale outbreaks in developing countries, which added to the capacity of the microorganism to cause Guillain-Barré syndrome (GBS), increasing the need for rapid and timely diagnosis to stop and prevent outbreaks. In this study, a loop-mediated isothermal amplification (LAMP) assay based on thecdtCgene was developed and evaluated for the rapid detection ofC. jejuni, using 91 strains for the standardization and validation. The LAMP assay was compared to whole-genome sequencing as the gold standard. The LAMP assay forC. jejunishowed a sensitivity of 100% (CI: 90.94 - 100%), a specificity of 100% (CI: 89.56 - 100%), a positive predictive value of 100% (CI: 90.94 - 100%) and a negative predictive value of 100% (CI: 89.56 - 100%). The assay demonstrated strong agreement between the LAMP assay and genomic sequencing (kappa value = 1). The LAMP assay based on thecdtCgene is a method that provides reliable and rapid results, with high sensitivity and specificity for the identification ofC. jejuni, and is considered a suitable alternative for the diagnosis of diarrheal infections by this pathogen in low-income countries.
Nutrient levels control root growth responses to high ambient temperature in plants
Authors: Lee Sanghwa , Showalter Julia , Zhang Ling , Cassin-Ross Gaëlle , Rouached Hatem , Busch Wolfgang 
Published: August 2023

AbstractGlobal warming will lead to significantly increased temperatures on earth. Plants respond to high ambient temperature with altered developmental and growth programs, termed thermomorphogenesis. Here we show that thermomorphogenesis is conserved in Arabidopsis, soybean, and rice and that it is linked to a decrease in the levels of the two macronutrients nitrogen and phosphorus. We also find that low external levels of these nutrients abolish root growth responses to high ambient temperature. We show that in Arabidopsis, this is due to the function of the transcription factorELONGATED HYPOCOTYL 5(HY5) and its transcriptional regulation of the transceptorNITRATE TRANSPORTER 1.1(NRT1.1). Soybean and Rice homologs of these genes are expressed consistently with a conserved role in regulating temperature responses in a nitrogen and phosphorus level dependent manner. Overall, our data show that root thermomorphogenesis is a conserved feature in species of the two major groups of angiosperms, monocots and dicots, that it leads to a reduction of nutrient levels in the plant, and that it is dependent on sufficient environmental nutrient supply, a regulatory process mediated by the HY5-NRT1.1 module.
Unlocking Predictive Power: A Machine Learning Tool Derived from In-Depth Analysis to Forecast the Impact of Missense Variants in Human Filamin C
Authors: Nagy Michael , Mlynek Georg , Kostan Julius , Smith Luke , Pühringer Dominic , Charron Philippe , Rasmussen Torsten Bloch , Bilinska Zofia , Akhtar Mohammed Majid , Syrris Petros , Lopes Luis R , Elliott Perry M , Gautel Mathias , Carugo Oliviero , Djinović-Carugo Kristina 
Published: August 2023

AbstractCardiomyopathies, diseases of the heart muscle, are a leading cause of heart failure. An increasing proportion of cardiomyopathies have been associated with specific genetic changes, such as mutations inFLNC, the gene that codes for filamin C. Altogether, more than 300 variants ofFLNChave been identified in patients, including a number of single point mutations. However, the role of a significant number of these mutations remains unknown. Here, we conducted a comprehensive analysis, starting from clinical data that led to identification of new pathogenic and non-pathogenicFLNCvariants. We selected some of these variants for further characterization that included studies ofin vivoeffects on the morphology of neonatal cardiomyocytes to establish links to phenotype, and thein vitrothermal stability and structure determination to understand biophysical factors impacting function. We used these findings to compile vast datasets of pathogenic and non-pathogenic variant structures and developed a machine-learning-based neural network (AMIVA-F) to predict the impact of single point mutations. AMIVA-F outperformed most commonly used predictors both in disease related as well as neutral variants, approaching ∼80% accuracy. Taken together, our study documents additionalFLNCvariants, their biophysical and structural properties, and their link to the disease phenotype. Furthermore, we developed a state-of-the-art web-based server AMIVA-F that can be used for accurate predictions regarding the effect of single point mutations in human filamin C, with broad implications for basic and clinical research.
Utilizing Heteroatom Types and Numbers from Extensive Ligand Libraries to Develop Novel hERG Blocker QSAR Models Using Machine Learning-based Classifiers
Authors: Haddad Safa , Oktay Lalehan , Erol Ismail , Şahin Kader , Durdagi Serdar 
Published: August 2023

AbstractThe human Ether-à-go-go Related Gene (hERG) channel plays a crucial role in membrane repolarization. Any disruptions in its function can lead to severe cardiovascular disorders like long QT syndrome (LQTS), which increases the risk of serious cardiovascular problems such as tachyarrhythmia and sudden cardiac death. Drug-induced LQTS is a significant concern and has resulted in drug withdrawals in the past. The main objective of this research study is to pinpoint crucial heteroatoms present in ligands that initiate interactions leading to effective blocking of the hERG channel. To achieve this aim, ligand-based quantitative structure-activity relationships (QSAR) models were constructed using extensive ligand libraries, considering the heteroatom types and numbers, and their associated hERG channel blockage pIC50values. Machine learning-assisted QSAR models were developed to analyze the key structural components influencing compound activity. Among various methods, the KPLS method proved to be the most efficient, allowing the construction of models based on eight distinct fingerprints. The study delved into investigating the influence of heteroatoms on the activity of hERG blockers, revealing their significant role. Furthermore, by quantifying the effect of heteroatom types and numbers on ligand activity at the hERG channel, six compound pairs were selected for molecular docking. Subsequent molecular dynamics (MD) simulations and MM/GBSA calculations per residue were performed to comprehensively analyze the interactions of the selected pair compounds.
Large-scale population genomics of Malayan pangolins reveals deep diversification and a new species
Authors: Li Bo , Lan Tianming , Wang Qing , Shi Minhui , Guo Ce , Li Haimeng , Liu Boyang , Liu Shanlin , Finch Kristen , Wang Shiqing , Yang Shangchen , Cui Liangyu , Li Jun , Zhao Xilong , Wang Jiangang , Deng Zhangwen , Wang Xinyu , Ma Yue , Kim Hyeon Jeong , Wasser Samuel K , Wang Kai , Lu Haorong , Yang Dongyi , Chen Jin , Guo Huabing , Yao Yan , Xie Hui , Wang Yiyi , Fan Jiale , Li Wangsheng , Niu Xiaotong , Hou Yinmeng , Yu Jieyao , Lu Jinyao , Li Siyuan , Qiu Zhaowen , Zhang Wei , Bai Suying , Han Lei , Wu Yuxin , Cai Xianchu , Huang Yunting , Wang Zhen , Wang Chen , Li Jiahao , Jiang Yuze , Liu Shasha , Wang Jiayi , Li Li , Hua Yan , Liu Huan , Xu Yanchun 
Published: August 2023

AbstractBackgroundArchipelagos and oceanic islands often present high percentage of endemism due to rapid speciation. The Malayan pangolin is a species distributing at both mainland (southern Yunnan, China) and oceanic islands via Malayan peninsula, which may result in deep differentiation among populations. In-depth investigation of population structure and genetic consequences for such species is of vital importance for their protection and conservation, practically for the critically endangered Malayan pangolin that is suffering from poaching, illegal trade, and habitat loss.ResultsHere we carried out a large-scale population genomic analysis for Malayan pangolins, and revealed three highly distinct genetic populations in this species, two of which are now being reported for the first time. Based on multiple lines of genomic and morphological evidence, we postulate the existence of a new pangolin species (Manis_1). Genetic diversity and recent inbreeding were both at a moderate level for both Malayan pangolins andManis_1, but mainland Malayan pangolins presented relatively lower genetic diversity, higher inbreeding and fitness cost than island populations.ConclusionsWe found extremely deep and graded differentiation in Malayan pangolins, with two newly discovered genetic populations and a new pangolin species that is closely related to the Philippine pangolin than the typical Malayan pangolin, but a distant relative of the Indian pangolin. Anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins, but mainland Malayan pangolins should be paid more attention for conservation due to higher genetic risks than island populations.
Assemblies, synapse clustering and network topology interact with plasticity to explain structure-function relationships of the cortical connectome
Authors: Ecker András , Egas Santander Daniela , Abdellah Marwan , Blanco Alonso Jorge , Bolaños-Puchet Sirio , Chindemi Giuseppe , Gowri Mariyappan Dhuruva Priyan , Isbister James B. , King James Gonzalo , Kumbhar Pramod , Magkanaris Ioannis , Muller Eilif B. , Reimann Michael W. 
Published: August 2023

AbstractSynaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have revealed mechanisms and protocols for the induction of plasticity between pairs of neurons, how these synaptic changes are coordinated in biological neuronal networks to ensure the emergence of learning remains poorly understood. Simulation and modeling have emerged as important tools to study learning in plastic networks, but have yet to achieve a scale that incorporates realistic network structure, active dendrites, and multi-synapse interactions, key determinants of synaptic plasticity. To rise to this challenge, we endowed an existing large-scale cortical network model, incorporating data-constrained dendritic processing and multi-synaptic connections, with a calcium-based model of functional plasticity that captures the diversity of excitatory connections extrapolated toin vivo-like conditions. This allowed us to study how dendrites and network structure interact with plasticity to shape stimulus representations at the microcircuit level. In our exploratory simulations, plasticity acted sparsely and specifically, firing rates and weight distributions remained stable without additional homeostatic mechanisms. At the circuit level, we found plasticity was driven by co-firing stimulus-evoked functional assemblies, spatial clustering of synapses on dendrites, and the topology of the network connectivity. As a result of the plastic changes, the network became more reliable with more stimulus-specific responses. We confirmed our testable predictions in the MICrONS datasets, an openly available electron microscopic reconstruction of a large volume of cortical tissue. Our results quantify at a large scale how the dendritic architecture and higher-order structure of cortical microcircuits play a central role in functional plasticity and provide a foundation for elucidating their role in learning.
Value co-creation in a high-performance computing (HPC) service ecosystem: opportunities for European SMEs
Authors: Bhattacharya Suman , Damij Nadja 
Published: August 2023

Purpose
This paper aims to develop a conceptual framework as a valuable investigative tool for future empirical studies examining stakeholders’ interactions within a high-performance computing (HPC) service ecosystem and identifying the enablers for better value co-creation under various service provisioning contexts.

Design/methodology/approach
This conceptual paper follows a theory adaptation research design that systematically examines the literature on a substantive topic encompassing HPC technology adoption and usage by European small and medium-sized enterprises (SMEs). Furthermore, it introduces theoretical perspectives from service innovation research as its methodological approach (method theory) to develop a theoretical framework for value co-creation within an HPC service ecosystem.

Findings
The conceptual framework presented in this paper identifies the critical resource elements of SMEs, which can potentially be integrated with other stakeholders’ resources and complement the limited internal resources of SMEs for enhanced value co-creation within an HPC service ecosystem.

Research limitations/implications
The conceptualisation of an HPC service ecosystem and the potential of value co-creation through integrating stakeholders’ resources, presented in this paper, underscore further empirical research in this direction.

Practical implications
Findings from this paper can inform European policymakers for regional development to frame regional strategies and policies that enable SMEs to better uptake HPC services. Service providers can revisit their business models to reconfigure their organisational resources for enhanced value proposition and co-creation.

Social implications
This study advances the agenda of transformative service research that aims uplifting changes and societal well-being through a more inclusive and sustainable value co-creation among a wider set of stakeholders within the service ecosystem.

Originality/value
The paper addresses an under-investigated research gap by examining SMEs’ adoption of HPC services and opportunities for higher value co-creation using a service ecosystem approach based on multi-actor interaction, collaboration and resource integration.