bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pacing intracellular Ca2+ signals in exocrine acinar cells
Authors: Yule David I. , Takano Takahiro 
Published: January 2024

AbstractAn increase in intracellular [Ca2+] in exocrine acinar cells resident in the salivary glands or pancreas is a fundamental event that drives fluid secretion and exocytosis of proteins. Stimulation with secretagogues initiates Ca2+ signals with precise spatiotemporal properties thought to be important for driving physiological output. Both in vitro, in acutely isolated acini, and in vivo, in animals expressing genetically encoded indicators, individual cells appear specialized to initiate Ca2+ signals upon stimulation. Furthermore, these signals appear to spread to neighbouring cells. These properties are present in the absence of a conventional pacemaker mechanism dependent on the cyclical activation of Ca2+‐dependent or Ca2+‐conducting plasma membrane ion channels. In this article, we propose a model for ‘pacing’ intracellular Ca2+ signals in acinar cells based on the enhanced sensitivity of a subpopulation of individual cells and the intercellular diffusion through gap junctions of inositol 1,4,5‐trisphosphate and Ca2+ to neighbouring cells.
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Impact of Cylinder-to-Cylinder Dispersion of Exhaust Gas Recirculation on the Three-Way Catalyst Performance and Tailpipe Emissions of Spark-Ignition Engines
Authors: Piqueras Pedro , de la Morena Joaquín , José Sanchis Enrique , Conde Carla 
Published: January 2024

Abstract
New generations of spark-ignition engines include exhaust gas recirculation (EGR) to improve the engine efficiency. Depending on the design of the EGR routing, some differences in the total amount of recirculated gases that reach each cylinder can be induced. This affects the air-to-fuel ratio on each cylinder due to the combination of the different temperature and composition of the gases at the intake valve closure. As a consequence, significant deviations in the combustion process and the subsequent composition upstream the three-way catalyst can be reached. This paper explores these effects on catalyst performance and tailpipe emissions, individualizing the behavior for each regulated species. The study was performed in a four-cylinder naturally aspirated engine with Atkinson cycle and a close-coupled three-way catalyst. The most significant deterioration in conversion efficiency appeared for the nitrogen oxides, directly linked to the EGR dispersion level. In the case of carbon monoxide (CO) emissions, no significant impact was observed except at high average EGR rates, where one or more of the cylinders exceeded the EGR tolerance for that speed and load. Based on these results, a strategy where the fuel injector command is adapted to correct the air-to-fuel ratio deviations induced by the EGR was developed and implemented.
Binding of GTP to BifA is required for the production of Pel-dependent biofilms in
Pseudomonas aeruginosa
Authors: Van Loon Jaime C. , Whitfield Gregory B. , Wong Nicole , O'Neal Lindsey , Henrickson Amy , Demeler Borries , O'Toole G. A. , Parsek Matthew R. , Howell P. Lynne 
Published: January 2024

ABSTRACT

The Pel exopolysaccharide is one of the most mechanistically conserved and phylogenetically diverse bacterial biofilm matrix determinants. Pel is a major contributor to the structural integrity of
Pseudomonas aeruginosa
biofilms, and its biosynthesis is regulated by the binding of cyclic-3′,5′-dimeric guanosine monophosphate (c-di-GMP) to the PelD receptor. c-di-GMP is synthesized from two molecules of guanosine triphosphate (GTP) by diguanylate cyclases with GGDEF domains and degraded by phosphodiesterases with EAL or HD-GYP domains. As the
P. aeruginosa
genome encodes 43 c-di-GMP metabolic enzymes, one way signaling specificity can be achieved is through direct interaction between specific enzyme-receptor pairs. Here, we show that the inner membrane hybrid GGDEF-EAL enzyme, BifA, directly interacts with PelD via its cytoplasmic HAMP, GGDEF, and EAL domains. Despite having no catalytic function, the degenerate active site motif of the BifA GGDEF domain (GGDQF) has retained the ability to bind GTP with micromolar affinity. Mutations that abolish GTP binding result in increased biofilm formation but stable global c-di-GMP levels. Our data suggest that BifA forms a dimer in solution and that GTP binding induces conformational changes in dimeric BifA that enhance the BifA-PelD interaction and stimulate its phosphodiesterase activity, thus reducing c-di-GMP levels and downregulating Pel biosynthesis. Structural comparisons between the dimeric AlphaFold2 model of BifA and the structures of other hybrid GGDEF-EAL proteins suggest that the regulation of BifA by GTP may occur through a novel mechanism.

IMPORTANCE

c-di-GMP is the most common cyclic dinucleotide used by bacteria to regulate phenotypes such as motility, biofilm formation, virulence factor production, cell cycle progression, and cell differentiation. While the identification and initial characterization of c-di-GMP metabolic enzymes are well established, our understanding of how these enzymes are regulated to provide signaling specificity remains understudied. Here we demonstrate that the inactive GGDEF domain of BifA binds GTP and regulates the adjacent phosphodiesterase EAL domain, ultimately downregulating Pel-dependent
P. aeruginosa
biofilm formation through an interaction with PelD. This discovery adds to the growing body of literature regarding how hybrid GGDEF-EAL enzymes are regulated and provides additional precedence for studying how direct interactions between c-di-GMP metabolic enzymes and effectors result in signaling specificity.
Clinical human metapneumovirus isolates show distinct pathogenesis and inflammatory profiles but similar CD8
+
T cell impairment
Authors: Sojati Jorna , Zhang Yu , Williams John V. 
Published: January 2024

ABSTRACT

Human metapneumovirus (HMPV) is a negative-sense single-stranded RNA virus in the
Pneumoviridae
family and a leading cause of acute upper and lower respiratory infections, particularly in children, immunocompromised patients, and the elderly. Although nearly every person is infected with HMPV during early childhood, re-infections occur often, highlighting difficulty in building long-term immunity. Inflammatory responses, including PD-1-mediated impairment of virus-specific CD8
+
T cells (T
CD8
), contribute to HMPV disease severity. HMPV strains are divided into four lineages: A1, A2, B1, and B2. However, little is known about immune responses to different viral subtypes. Here, we characterize responses to four HMPV clinical isolates—TN/94-344 (A1), TN/94-49 (A2), C2-202 (B1), and TN/96-35 (B2)—
in vivo
in C57BL/6 (B6) mice. TN/94-49 was avirulent, while TN/94-344, C2-202, and TN/96-35 showed varying degrees of weight loss and clinical disease. Differences in disease did not correlate to virus burden in upper or lower tracts. TN/94-49 HMPV exhibited highest nose titers and delayed lung clearance. Cytokine profiles differed between HMPV isolates, with TN/96-35 inducing the broadest lung inflammatory cytokines. TN/96-35 also showed lower HMPV burden and less weight loss than other virulent isolates, suggesting a more efficient antiviral response. Interestingly, disease correlated with higher expression of T-cell chemoattractant CXCL9. All isolates elicited PD-1 upregulation and decreased IFNγ and CD107a expression in virus-specific T
CD8
, with little difference between HMPV subtypes. This work uncovers previously uncharacterized variations in immune responses to clinical HMPV isolates of different lineages.

IMPORTANCE

This study extensively explored differences in T-cell-mediated immunity between human metapneumovirus (HMPV) clinical isolates. Much existing HMPV research has been done with strains passaged extensively in cell lines, likely acquiring mutations advantageous to
in vitro
replication. Clinical isolates are collected directly from human patients and have undergone <10 passages, serving as more physiologically relevant models of HMPV infection. Additionally, existing animal studies of HMPV disease mainly focus on lung pathogenesis, while HMPV infects both upper and lower airways of humans. This work highlights distinct differences in HMPV burden in upper and lower tracts between clinical isolates. Lastly, this study uniquely explores differences in host immunity between all four HMPV genetic lineages. The predominant HMPV subtype in circulation varies seasonally; thus, understanding host responses to all subgroups is critical for developing effective HMPV vaccines.
Graphene oxide and bacteria interactions: what is known and what should we expect?
Authors: Simeonova Diliana D. , Pollmann Katrin , Bianco Alberto , Lièvremont Didier 
Published: January 2024

ABSTRACT
Graphene oxide (GO) and graphene-based materials (GBMs) have gained over the last two decades considerable attention due to their intrinsic physicochemical properties and their applications. Besides, a lot of concern regarding the potential toxicity of GBMs has emerged. One of the aspects of concern is the interactions between GBMs and different environmental compartments, especially indigenous microbial and, in particular, bacterial communities. Recent research showed that GO and GBMs impacted bacterial pure culture or bacterial communities; therefore, these interactions have to be further studied to better understand and assess the fate of these materials in the environment. Here, we present our opinion and hypotheses related to possible degradation mechanisms of GO that can be used by environmental bacteria. This work is the first attempt to deduce and summarize plausible degradation pathways of GO, from structurally similar recalcitrant and toxic compounds, such as polyaromatic hydrocarbons.
Challenging diagnosis of IgM multiple myeloma
Authors: Mahmood Fatima , Ahmed Basem , Thalody Vimala , Mehdi Syed 
Published: January 2024

IgM monoclonal gammopathies such as IgM myeloma and Waldenström macroglobulinaemia are distinct haematological conditions; however, differentiating between these entities can often present as a challenge.In this review, we explore the challenging diagnosis and treatment of IgM myeloma in a patient presenting with unexplained macrocytic anaemia, elevated serum protein and IgM levels in the absence of t(11;14) and lytic bone lesions that are classically associated with the diagnosis of IgM myeloma. The diagnosis was established based on 40% monoclonal plasma cell population on a bone marrow biopsy, gain of 1q21 on fluorescence in situ hybridisation, cyclin D1 positivity and absence of MYD88 mutation.
Association of GLP-1 secretion with parameters of glycemic control in women after gestational diabetes mellitus
Authors: Pappa Eleni , Busygina Kristina , Harada Saori , Hermann Hana , Then Cornelia , Lechner Andreas , Ferrari Uta , Seissler Jochen 
Published: January 2024

IntroductionWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes, while the exact mechanisms underlying its pathophysiology are still unclear. We investigated the association of glucagon-like peptide-1 (GLP-1) response to oral glucose with parameters of glycemic control in women with previous GDM in the prospective PPSDiab (Prediction, Prevention, and Subclassification of Type 2 Diabetes) study.Research design and methodsGlucose metabolism parameters and GLP-1 secretion were analyzed during oral glucose tolerance test (OGTT) in women with previous GDM (n=129) and women with a history of normal glucose tolerance (n=67) during pregnancy (controls). First- and second-phase insulin and GLP-1 secretion in relation to plasma glucose (PG) levels were assessed, and development of pre-diabetes was analyzed after 5-year follow-up among women with previous GDM and a normal glycemic state at baseline (n=58).ResultsThe area under the curve (AUC during the OGTT 0–120 min) of PG and insulin but not GLP-1 differed significantly between post-GDM women and controls. However, women with previous GDM had a significantly decreased GLP-1 response in relation to PG and plasma insulin during the second phase of the OGTT. After a follow-up of 5 years, 19.0% post-GDM women with a normal glycemic state at the baseline visit developed abnormal glucose metabolism. The total, first- and second-phase AUC GLP-1/PG and GLP-1/insulin ratios were not associated with development of abnormal glucose tolerance.ConclusionsWomen with previous GDM showed a reduced GLP-1 response in relation to PG and insulin concentrations indicating early abnormalities in glucose metabolism. However, the altered GLP-1 response to oral glucose did not predict progression to pre-diabetes and type 2 diabetes in the first 5 years after GDM.
Investigating the role of iron status in the development of coeliac disease: a Mendelian randomisation study
Authors: Hujoel Isabel A , Hujoel Margaux Louise Anna 
Published: January 2024

ObjectiveThe environmental trigger behind the increasing prevalence of coeliac disease is not known. One suggested cause is iron deficiency, which is common in coeliac disease. We aimed to evaluate this possible association with Mendelian randomisation (MR), which under certain assumptions can suggest a causal relationship.DesignWe conducted a two-sample MR study examining the relationship between single nucleotide polymorphisms (SNPs) associated with iron status and the presence of coeliac disease. The SNPs were drawn from a meta-analysis of three genome-wide association studies (GWAS). The association between these SNPs and coeliac disease was assessed using GWAS summary statistics from the UK Biobank. This consists of 336 638 white British individuals, 1855 with coeliac disease. We performed an MR Egger test for pleiotropy and assessed the plausibility of the assumptions of MR to evaluate for possible causality.ResultsThere were four SNPs strongly associated with systemic iron status. These were not associated with known risk factors for coeliac disease. All four SNPs were available in the UK Biobank coeliac disease summary statistics. Harmonising exposure and outcome associations, we found that higher iron status was negatively associated with risk of coeliac disease (OR per 1 SD increase in serum iron: 0.65, 95% CI 0.47 to 0.91). Leave-one-out analyses had consistent results, and no single SNP drove the association. All three assumptions of MR appeared plausible.ConclusionWe found that genetically lower iron levels were associated with an increased risk of coeliac disease. Our findings highlight a potential opportunity for coeliac disease prevention.
Subthalamic stimulation has acute psychotropic effects and improves neuropsychiatric fluctuations in Parkinson’s disease
Authors: Magalhães Andreia D , Amstutz Deborah , Petermann Katrin , Debove Ines , Sousa Mário , Maradan-Gachet Marie E , Lachenmayer Martin Lenard , Waskönig Julia , Murcia-Carretero Sandra , Diamantaras Andreas Antonios , Tinkhauser Gerd , Nowacki Andreas , Pollo Claudio , Rodriguez-Blazquez Carmen , Martinez-Martin Pablo , Krack Paul 
Published: January 2024

BackgroundSubthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for motor complications in Parkinson’s disease (PD). However, its effects on neuropsychiatric symptoms remain disputed. The aim of this study was to evaluate the effects of STN-DBS on neuropsychiatric symptoms in PD.MethodsWe retrospectively assessed 26 patients with PD who underwent a preoperative levodopa challenge and postoperative levodopa and stimulation challenges 1 year after STN-DBS. Based on the Neuropsychiatric Fluctuations Scale, Neuropsychiatric State Scores and Neuropsychiatric Fluctuation Indices (NFIs) were calculated. Mixed-effects models with random effects for intercept were used to examine the association of Neuropsychiatric State Score and NFI with the different assessment conditions.ResultsIn acute challenge conditions, there was an estimated increase of 15.9 points in the Neuropsychiatric State Score in stimulation ON conditions (95% CI 11.4 to 20.6, p<0.001) and 7.6 points in medication ON conditions (95% CI 3.3 to 11.9, p<0.001). Neuropsychiatric fluctuations induced by levodopa, quantified with NFI, decreased by 35.54% (95% CI 49.3 to 21.8, p<0.001) 1 year after STN-DBS.ConclusionsBilateral STN-DBS at therapeutic parameters has acute psychotropic effects similar to levodopa and can modulate and decrease levodopa-induced neuropsychiatric fluctuations.
Lifestyle predictors of colorectal cancer in European populations: a systematic review
Authors: Mertens Elly , Keuchkarian Maria , Vasquez Maria Salve , Vandevijvere Stefanie , Peñalvo José L 
Published: January 2024

BackgroundColorectal cancer (CRC) is the second most prevalent cancer in Europe, with one-fifth of cases attributable to unhealthy lifestyles. Risk prediction models for quantifying CRC risk and identifying high-risk groups have been developed or validated across European populations, some considering lifestyle as a predictor.PurposeTo identify lifestyle predictors considered in existing risk prediction models applicable for European populations and characterise their corresponding parameter values for an improved understanding of their relative contribution to prediction across different models.MethodsA systematic review was conducted in PubMed and Web of Science from January 2000 to August 2021. Risk prediction models were included if (1) developed and/or validated in an adult asymptomatic European population, (2) based on non-invasively measured predictors and (3) reported mean estimates and uncertainty for predictors included. To facilitate comparison, model-specific lifestyle predictors were visualised using forest plots.ResultsA total of 21 risk prediction models for CRC (reported in 16 studies) were eligible, of which 11 were validated in a European adult population but developed elsewhere, mostly USA. All models but two reported at least one lifestyle factor as predictor. Of the lifestyle factors, the most common predictors were body mass index (BMI) and smoking (each present in 13 models), followed by alcohol (11), and physical activity (7), while diet-related factors were less considered with the most commonly present meat (9), vegetables (5) or dairy (2). The independent predictive contribution was generally greater when they were collected with greater detail, although a noticeable variation in effect size estimates for BMI, smoking and alcohol.ConclusionsEarly identification of high-risk groups based on lifestyle data offers the potential to encourage participation in lifestyle change and screening programmes, hence reduce CRC burden. We propose the commonly shared lifestyle predictors to be further used in public health prediction modelling for improved uptake of the model.
Vegetarian and plant-based diets associated with lower incidence of COVID-19
Authors: Acosta-Navarro Júlio César , Dias Laís Ferreira , de Gouveia Luiza Antoniazzi Gomes , Ferreira Emerson Pinheiro , de Oliveira Marcos Vinnícius Pires Fernandes , Marin Flávia Andréia , Oliveira José Valter Costa , da Silva Andressa Candida , Silva Isabella Louise , Freitas Fabiane de Oliveira , Soares Paulo Rogerio 
Published: January 2024

ObjectiveTo evaluate the influence of dietary patterns on the incidence and evolution of COVID-19. We hypothesised that a plant-based diet or a vegetarian diet compared with an omnivorous diet might be associated with a lower incidence of COVID-19 infection and severity in those infected.DesignIn this observational study, 702 participants provided information on sociodemographic characteristics, dietary information and COVID-19 outcomes between March and July of 2022. Individuals were divided into two groups based on their dietary habits, omnivorous (n=424) and plant-based (n=278). The plant-based group was further divided into vegetarian and flexitarian subgroups. The groups were compared with respect to the incidence of COVID-19 infection, severity and duration. We used multivariable logistic regression models to evaluate the influence of dietary patterns.ResultsPlant-based and vegetarian groups had a higher intake of vegetables, legumes and nuts, and lower intake of dairy and meat. After adjusting for important confounders, such as body mass index, physical activity and pre-existing medical conditions, the plant-based diet and vegetarian group had 39% (OR=0.61, 95% CI 0.44 to 0.85; p=0.003) and 39% (OR 0.61, 95% CI 0.42 to 0.88; p=0.009) lower odds of the incidence of COVID-19 infection, respectively, compared with the omnivorous group. No association was observed between self-reported diets and COVID-19 severity or duration.ConclusionPlant-based and mainly vegetarian diets were associated with a lower incidence of COVID-19 infection. These dietary patterns may be considered protective against COVID-19 infection. (Study protocol registered in CAAE: 54351421.4.0000.0068.)
Longitudinal symptom profile of palliative care patients receiving a nurse-led end-of-life (PEACH) programme to support preference to die at home
Authors: Agar Meera , Xuan Wei , Lee Jessica , Barclay Gregory , Oloffs Alan , Jobburn Kim , Harlum Janeane , Maurya Nutan , Chow Josephine Sau Fan 
Published: January 2024

ObjectivesTailored models of home-based palliative care aimed to support death at home, should also ensure optimal symptom control. This study aimed to explore symptom occurrence and distress over time in Palliative Extended And Care at Home (PEACH) model of care recipients.DesignThis was a prospective cohort study.Setting and participantsParticipants were consecutive recipients of the PEACH rapid response nurse-led model of care in metropolitan Sydney (December 2013–January 2017) who were in the last weeks of life with a terminal or deteriorating phase of illness and had a preference to be cared or die at home.Outcome measuresDeidentified data including sociodemographic and clinical characteristics, and symptom distress scores (Symptom Assessment Score) were collected at each clinical visit. Descriptive statistics and forward selection logistic regression analysis were used to explore influence of symptom distress levels on mode of separation ((1) died at home while still receiving a PEACH package, (2) admitted to a hospital or an inpatient palliative care unit or (3) discharged from the package (alive and no longer requiring PEACH)) across four symptom distress level categories.Results1754 consecutive clients received a PEACH package (mean age 70 years, 55% male). 75.7% (n=1327) had a home death, 13.5% (n=237) were admitted and 10.8% (n=190) were still alive and residing at home when the package ceased. Mean symptom distress scores improved from baseline to final scores in the three groups (p<0.0001). The frequency of no symptom distress score (0) category was higher in the home death group. Higher scores for nausea, fatigue, insomnia and bowel problems were independent predictors of who was admitted.ConclusionTailored home-based palliative care models to meet preference to die at home, achieve this while maintaining symptom control. A focus on particular symptoms may further optimise these models of care.