bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter
Authors: Castiglioni Silvia , Pezzoli Laura , Pezzani Lidia , Lettieri Antonella , Di Fede Elisabetta , Cereda Anna , Ancona Silvia , Gallina Andrea , Colombo Elisa Adele , Parodi Chiara , Grazioli Paolo , Taci Esi , Milani Donatella , Iascone Maria , Massa Valentina , Gervasini Cristina 
Published: December 2024

Abstract
Background
the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain.

Results
through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.1 and a splicing variant in Pt.2 associated with mild phenotype. PPP3CA is ubiquitously expressed with tissue-specificity of; namely, splicing isoform 1 prevailing over isoform 2 in the central nervous system. By analyzing isoform distribution in patient-derived cell lines, we highlight a skewed expression of both isoforms in Pt.1, whereas only isoform 2 shows a moderate reduction in Pt.2. In contrast, we did not observe significant abundance changes at the protein level. Cell lines derived from Pt.1 showed a reduced proliferation, associated with an increase in cell death and the upregulation of the unfolded protein response (UPR) pathway.

Conclusion
data suggest that an aberrant PPP3CA protein in Pt.1 could lead to UPR activation resulting in increased cell death. In Pt.2 an imbalance between the two main isoforms possibly explains the peculiar pathological manifestations, such as a moderate developmental delay.
Conventional versus task-based package organization for out-of-hospital emergency kits: an emergency medical services simulation study
Authors: Laxar Daniel , Grassmann Daniel , Reischmann Lena , Kaider Alexandra , Schadler Bertram , Huber Carmen , Krammel Mario , Hafner Christina 
Published: December 2024

Abstract
Background
Emergency Medical Service crews are equipped with comprehensive emergency kits for routine care and to provide life-saving interventions in severely ill patients. While guidelines on contents and packing strategies of emergency kits for specific tasks and specialized situations exist, data for the design of out-of-hospital emergency kits in a general urban population is lacking. It may be possible to transfer the promising results of modern in-hospital packing strategies such as task-based package organization (TPO) to an Emergency Medical Service setting.

Methods
Four types of emergency kit were used in this study: two novel backpack emergency kits were acquired for this study (one packed using a TPO approach (PAX bags) and the other a traditional non-TPO approach (inter-rescue)); the existing emergency kit; and a TPO-repack of the existing kit. We recruited 80 paramedics who each performed four different tasks in a simulated setting: preparation for endotracheal intubation; preparing an intravenous access and a crystalloid infusion; preparing intraosseous access with medication; and preparing for a forearm splint. Questionnaires were completed before starting, after each task, and at the end of each study session.

Results
There was no overall difference for the primary outcome of task completion between the novel TPO and novel non-TPO kit (p = 0.11). However, for selected tasks (forearm splint) completion time was significantly different between these kits. Overall, participants performed fastest when using the existing emergency kit. Participants frequently omitted items required for critical procedures, regardless of kit type.

Conclusion
TPO has been previously investigated in an in-hospital setting using participants with low exposure to medical emergencies, and with promising results. In our prehospital simulation setting with paramedics, equipment retrieval was neither faster nor more complete compared to non-TPO kits.
Veno-venous extracorporeal membrane oxygenation as a bridge in central airway obstruction: experience from a high-volume center
Authors: Luo Xiao-xiu , Li Jia-jia , Yang Fu-xun , Lei Yu , Zeng Fan , Lan Yun-ping , Pan Chun , Huang Xiao-bo , Liu Rong-an , Luo Jing-chao 
Published: December 2024

Abstract
Background
Perioperative airway management and oxygenation maintenance during central airway obstruction (CAO) treatment pose great challenges. While veno-venous extracorporeal membrane oxygenation (V-V ECMO) shows promise as a bridge therapy, optimal implementation and management strategies remain lacking. We present our experience with V-V ECMO in CAO management from a high-volume center.

Methods
We retrospectively analyzed 29 consecutive patients who received V-V ECMO support for CAO between 2015 and 2023. Patient demographics, clinical characteristics, ECMO cannulation and operation parameters, interventional procedures, complications, and outcomes were reviewed.

Results
Among patients with median airway diameter of 4.5 mm (IQR 2–5 mm), etiologies included primary tumors (n = 17), metastases (n = 7), and post-intubation/tracheostomy stenosis (n = 5). Treatment comprised bronchoscopic interventions (n = 9) and surgical procedures (thoracic = 15, head/neck = 5). Using predominantly femoral-jugular cannulation (n = 27), we implemented a minimal anticoagulation protocol (catheter flush with 5U/mL heparin only). All patients survived through 6-month follow-up with minimal ECMO-related complications.

Conclusion
The application of V-V ECMO with minimal anticoagulation demonstrates safety and efficacy as a bridging support in the therapeutic approach to CAO.
Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases
Authors: Liu Haiyi , Yuan Yonghui , Johnson-Stephenson Takerra K. , Jing Chenyang , Zhang Mingchao , Huang Jun , Zen Ke , Li Limin , Zhu Dihan 
Published: December 2024

Abstract
Background
macrophage-targeting therapy of ischemic disease has made progress in clinic trial. However, the role and underlying mechanism of pro-inflammatory or anti-inflammatory polarized macrophages in modulating ischemic diseases remain incompletely understood.

Results
here we examine the effect of pro-inflammatory (LPS) and anti-inflammatory (IL-4) macrophage on ischemic diseases in a mouse ischemic hindlimb and heart model, and identify that signal regulatory protein α (Sirpα) modulates macrophage polarization induced angiogenesis via promoting phagocytosis or activating HIF1α nucleus relocation in macrophages, respectively. More importantly, the therapeutic effect of polarized macrophages is controlled by Sirpα in a time-dependent manner. Downregulation of macrophage Sirpα at the early-stage or upregulation of macrophage Sirpα at the late-stage of ischemic disease enhances the therapeutic effect. In contrast, increasing Sirpα at the early-stage or decreasing it at the late-stage leads to failure of inducing ischemic disease resilience. Mechanistically, we find that signal transducer and activator of transcription 3 and 6 (Stat3 and Stat6) mediate downregulation (pro-inflammatory polarization) or upregulation (anti-inflammatory polarization) of Sirpα, respectively.

Conclusion
Our results reveal that dynamic regulation of macrophage by Sirpα plays a critical role in alleviating ischemic diseases.
Baicalin alleviates intestinal inflammation and microbial disturbances by regulating Th17/Treg balance and enhancing Lactobacillus colonization in piglets
Authors: Zhang Shunfen , Luo Chengzeng , Li Kai , Wang Junhong , Wang Huixin , Zhong Ruqing , Chen Liang , Ma Qiugang , Zhang Hongfu 
Published: December 2024

Abstract
Background
Intestinal inflammation is a common and serious health problem in piglet production, especially enteritis caused by pathogenic Escherichia coli (E. coli). This condition often leads to high mortality, slow weight gain, and significant economic losses.

Results
In this study, we isolated an E. coli strain, SKLAN202302, from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin. Piglets infected with E. coli exhibited significant reductions in body weight, feed intake, small intestine length, and ileal goblet cell count (P < 0.05), along with deteriorated ileal morphology. However, baicalin supplementation resulted in body weights, feed intake, and intestinal morphology similar to those of the control group. Notably, there was a significant increase in the colonization of Lactobacillus species, particularly Lactobacillus_reuteri, Lactobacillus_amylovorus, and Lactobacillus_johnii, compared to the E. coli group (P < 0.05). At the metabolic and transcriptional levels, E. coli infection increased inflammatory mediators, including eicosanoids (leukotriene F4, prostaglandin F1a, leukotriene E4, thromboxane B2, prostaglandin G2, and PGH2), monosaccharides, and TCA cycle intermediates (oxoglutaric acid, glutaric acid, adipic acid, citric acid, and isocitric acid) in the ileum. It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway (CTLA4, IFN-ALPHA-8, IL12RB2, TRAV3, TRAV16, FOS, and VEGFA), as well as inflammatory factors. Conversely, baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids [including lysoPC (P-18:1(9Z)/0:0), PC (17:0/0:0), lysoPC (16:1(9Z)/0:0), PC (18:0/0:0), lysoPC (18:0/0:0), PA (10:0/i-16:0), and PA (10:0/8:0)] and amino acids. It also regulated genes within the IL-17 signaling pathway (IL4, CCL17, CXCL10, IFNG, and CXCL2), suggesting a mechanism by which baicalin mitigates E. coli-induced intestinal and microbial disturbances. Subsequent flow cytometry analysis showed that E. coli infection increased the numbers of CD3+ and Foxp3+ cells, decreased IL-17A+ cells, and reduced Th17/Treg ratios. Baicalin supplementation restored these parameters to control levels.

Conclusions
Baicalin supplementation effectively alleviates E. coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization, counteracting inflammatory mediators, and regulating immune-related gene expression and the Th17/Treg balance. These findings highlight baicalin’s potential in alleviating intestinal inflammation.

Graphical abstract
Metabolic modelling uncovers the complex interplay between fungal probiotics, poultry microbiomes, and diet
Authors: Al-Nijir Montazar , Chuck Christopher J. , Bedford Michael R. , Henk Daniel A. 
Published: December 2024

Abstract
Background
The search for alternatives to antibiotic growth promoters in poultry production has increased interest in probiotics. However, the complexity of the interactions between probiotics, gut microbiome, and the host hinders the development of effective probiotic interventions. This study explores metabolic modelling to examine the possibility of designing informed probiotic interventions within poultry production.

Results
Genomic metabolic models of fungi were generated and simulated in the context of poultry gut microbial communities. The modelling approach correlated with short-chain fatty acid production, particularly in the caecum. Introducing fungi to poultry microbiomes resulted in strain-specific and diet-dependent effects on the gut microbiome. The impact of fungal probiotics on microbiome diversity and pathogen inhibition varied depending on the specific strain, resident microbiome composition, and host diet. This context-dependency highlights the need for tailored probiotic interventions that consider the unique characteristics of each poultry production environment.

Conclusions
This study demonstrates the potential of metabolic modelling to elucidate the complex interactions between probiotics, the gut microbiome, and diet in poultry. While the effects of specific fungal strains were found to be context-dependent, the approach itself provides a valuable tool for designing targeted probiotic interventions. By considering the specific characteristics of the host microbiome and dietary factors, this methodology could guide the deployment of effective probiotics in poultry production. However, the current work relies on computational predictions, and further in vivo validation studies are needed to confirm the efficacy of the identified probiotic candidates. Nonetheless, this study represents a significant step in using metabolic models to inform probiotic interventions in the poultry industry.
Paradoxical attenuation of early amyloid-induced cognitive impairment and synaptic plasticity in an aged APP/Tau bigenic rat model
Authors: Emmerson Joshua T. , Do Carmo Sonia , Lavagna Agustina , Huang Chunwei , Wong Tak Pan , Martinez-Trujillo Julio C. , Cuello A. Claudio 
Published: December 2024

AbstractThe combination of amyloid beta and tau pathologies leads to tau-mediated neurodegeneration in Alzheimer’s disease. However, the relative contributions of amyloid beta and tau peptide accumulation to the manifestation of the pathological phenotype in the early stages, before the overt deposition of plaques and tangles, are still unclear. We investigated the longitudinal pathological effects of combining human-like amyloidosis and tauopathy in a novel transgenic rat model, coded McGill-R-APPxhTau. We compared the effects of individual and combined amyloidosis and tauopathy in transgenic rats by assessing the spatiotemporal progression of Alzheimer’s-like amyloid and tau pathologies using biochemical and immunohistochemical methods. Extensive behavioral testing for learning and memory was also conducted to evaluate cognitive decline. Additionally, we investigated brain inflammation, neuronal cell loss, as well as synaptic plasticity through acute brain slice electrophysiological recordings and Western blotting. Evaluation of Alzheimer’s-like amyloidosis and tauopathy, at the initial stages, unexpectedly revealed that the combination of amyloid pathology with the initial increment in phosphorylated tau exerted a paradoxical corrective effect on amyloid-induced cognitive impairments and led to a compensatory-like restoration of synaptic plasticity as revealed by electrophysiological evidence, compared to monogenic transgenic rats with amyloidosis or tauopathy. We discovered elevated CREB phosphorylation and increased expression of postsynaptic proteins as a tentative explanation for the improved hippocampal synaptic plasticity. However, this tau-induced protective effect on synaptic function was transient. As anticipated, at more advanced stages, the APPxhTau bigenic rats exhibited aggravated tau and amyloid pathologies, cognitive decline, increased neuroinflammation, and tau-driven neuronal loss compared to monogenic rat models of Alzheimer’s-like amyloid and tau pathologies. The present findings propose that the early accumulation of phosphorylated tau may have a transient protective impact on the evolving amyloid pathology-derived synaptic impairments.
Controlled low strength material modified with lignosulfonate
Authors: Heo Yoon Geom , Son Dong Geon , Babatunde Quadri Olakunle , Byun Yong-Hoon 
Published: December 2024

AbstractControlled low-strength materials (CLSM) have been used for conventional backfilling and structural filling owing to their flowability, self-consolidating, and self-leveling features. This study investigates the rheological, mechanical, and dynamic characteristics of lignosulfonate-modified CLSM. The elemental analysis of lignosulfonate reveals the presence of various elements and an irregular morphology, as observed using a scanning electron microscope. A series of tests, including flow tests, Vicat needle tests, uniaxial compression tests, and shear wave monitoring, are conducted to evaluate the flowability, setting time, strength, and shear wave velocity of lignosulfonate-modified CLSM. The experimental results show that the flowability and initial and final setting times of the CLSM mixtures increase with increasing lignosulfonate content (LC), which improves workability in the field but results in a slight strength loss. Regarding the uniaxial compressive strength, CLSM mixtures with lower LC exhibit a rapid increase in strength during the early stages, while those with higher LC show higher performance on the 14th day of curing. In contrast, an LC of 0.21% led to a slight reduction in the strength on the 28th day. The current study also shows an exponential correlation between the uniaxial compressive strength and shear wave velocity.
Understanding deviations from original equipment manufacturers’ maintenance recommendations: reasons, barriers, and benefits
Authors: Okirie Ahiamadu Jonathan , Barnabas Mack , Ejomarie Ewomazino , Asomie Asomie Stephen 
Published: December 2024

AbstractUnderstanding why maintenance professionals deviate from OEM maintenance recommendations is essential. These recommendations are crucial for ensuring equipment reliability, safety, and performance over its operational lifecycle. However, deviations from these guidelines are common and can occur for various reasons. This study seeks to enhance maintenance practices by analyzing the reasons for deviations (RFD) from OEM maintenance recommendations, identifying the barriers to adherence (BTA), and exploring the potential benefits (PB) of such deviations. To achieve this objective, a survey was conducted in Port Harcourt, Southern Nigeria, involving 105 maintenance personnel from three maintenance-intensive sectors: Oil and Gas, Energy, and Petrochemicals, the study achieved response rates of, 78%, 82%, and 92% respectively. Through qualitative evaluation of the response data, the research identified cost considerations and operational constraints as primary reasons for non-adherence to OEM guidelines. Respondents highlighted benefits such as cost savings and enhanced equipment availability, citing limited budgets and operational demands as significant barriers to compliance. Comparative analysis across the three deviant factors (RFD, BTA, and PB) underscores the dominance of cost-related factors and operational constraints in driving deviations, alongside technological influences, that both facilitate and impede adherence. Environmental and organizational factors, though influential, exhibit comparatively lesser impact. These findings highlight the significance of aligning maintenance practices with OEM recommendations. This alignment not only enhances equipment reliability and reduces operational risks but also has the potential to improve maintenance practices, foster innovation in the industry, and ultimately optimize equipment performance and reliability in industrial settings.
Indigenous–non-Indigenous disparities in health and social outcomes 5 years after first episode psychosis: national cohort study
Authors: Cunningham Ruth , Petrović-van der Deen Frederieke , Gibb Sheree , Crowe Marie , Manuel Jenni , Pitama Suzanne , Crengle Sue , Porter Richard , Lacey Cameron 
Published: December 2024

Background
There are ethnic differences, including differences related to indigeneity, in the incidence of first episode psychosis (FEP) and pathways into care, but research on ethnic disparities in outcomes following FEP is limited.

Aims
In this study we examined social and health outcomes following FEP diagnosis for a cohort of Māori (Indigenous people of New Zealand) and non-Māori (non-Indigenous) young people. We have focused on understanding the opportunities for better outcomes for Māori by examining the relative advantage of non-Māori with FEP.

Method
Statistics New Zealand's Integrated Data Infrastructure was accessed to describe mental health and social service interactions and outcomes for a retrospective FEP cohort comprising 918 young Māori and 1275 non-Māori aged 13 to 25 at diagnosis. Logistic regression models were used to examine whether social outcomes including employment, benefit receipt, education and justice involvement in year 5 differed by indigeneity.

Results
Non-Māori young people were more likely than Māori to have positive outcomes in the fifth year after FEP diagnosis, including higher levels of employment and income, and lower rates of benefit receipt and criminal justice system involvement. These patterns were seen across diagnostic groups, and for both those receiving ongoing mental healthcare and those who were not.

Conclusions
Non-Māori experience relative advantage in outcomes 5 years after FEP diagnosis. Indigenous-based social disparities following FEP urgently require a response from the health, education, employment, justice and political systems to avoid perpetuating these inequities, alongside efforts to address the disadvantages faced by all young people with FEP.
Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells
Authors: Buckley Yuli , Stoll Maria S. K. , Hoppel Charles L. , Mears Jason A. 
Published: December 2024

ABSTRACT
In response to external stress, mitochondrial dynamics is often disrupted, but the associated physiologic changes are often uncharacterized. In many cancers, including glioblastoma (GBM), mitochondrial dysfunction has been observed. Understanding how mitochondrial dynamics and physiology contribute to treatment resistance will lead to more targeted and effective therapeutics. This study aims to uncover how mitochondria in GBM cells adapt to and resist ionizing radiation (IR), a component of the standard of care for GBM. Using several approaches, we investigated how mitochondrial dynamics and physiology adapt to radiation stress, and we uncover a novel role for Fis1, a pro-fission protein, in regulating the stress response through mitochondrial DNA (mtDNA) maintenance and altered mitochondrial bioenergetics. Importantly, our data demonstrate that increased fission in response to IR leads to removal of mtDNA damage and more efficient oxygen consumption through altered electron transport chain (ETC) activities in intact mitochondria. These findings demonstrate a key role for Fis1 in targeting damaged mtDNA for degradation and regulating mitochondrial bioenergetics through altered dynamics.
Fatty acid profiles and tolerance to temperature extremes in Daphnia pulex
Authors: Pecl Ivan , Blier Pierre U. , Dufresne France 
Published: December 2024

ABSTRACT
Identification of physiological processes setting thermal tolerance limits is essential to describing adaptive response to temperature changes. We used the North American Daphnia pulex complex, which makes a remarkable model for comparative physiology as it is composed of clones differing in heat tolerance and ploidies, and with a wide geographic distribution. The fatty acid composition of 18 diploid and triploid D. pulex clones acclimated to 16°C and 24°C was measured and compared with their tolerance to extreme high and low temperatures (CTmax and CTmin, respectively). Eicosapentaenoic acid (EPA) relative content showed a strong negative relationship with CTmax and a clear association with CTmin. Higher unsaturation and peroxidation indices were associated with better cold tolerance, whereas saturated fatty acids and monounsaturated fatty acids were associated with lower cold tolerance. Triploid D. pulex clones accumulated more EPA and had lower CTmin than diploid clones (better cold tolerance). Triploid clones retained more omega-6 polyunsaturated fatty acids at high temperature. CTmax was positively correlated with CTmin, suggesting the existence of important constraints in temperature tolerance caused by fatty acid composition.