bluuebunny/crossref_metadata_2025 huggingface dataset:
The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?
Authors: Fodor M. , Salcher S. , Gottschling H. , Mair A. , Blumer M. , Sopper S. , Ebner S. , Pircher A. , Oberhuber R. , Wolf D. , Schneeberger S. , Hautz T.
Published: October 2022

The liver has been proposed as an important “immune organ” of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organsex vivowhile testing for organ quality and function prior to transplantation. As for the liver, hypothermic and normothermic MP techniques have successfully been implemented in clinically routine, especially for the use of marginal donor livers. Although there is evidence that ischemia reperfusion injury-associated inflammation is reduced in machine-perfused livers, little is known whether MP impacts the quantity, activation state and function of the hepatic immune-cell repertoire, and how this affects the inflammatory milieu during MP. At this point, it remains even speculative if liver-resident immune cells primarily exert a pro-inflammatory and hence destructive effect on machine-perfused organs, or in part may be essential to induce liver regeneration and counteract liver damage. This review discusses the role of hepatic immune cell subtypes during inflammatory conditions and ischemia reperfusion injury in the context of liver transplantation. We further highlight the possible impact of MP on the modification of the immune cell repertoire and its potential for future applications and immune modulation of the liver.
Comprehensive characterization of extracellular matrix-related genes in PAAD identified a novel prognostic panel related to clinical outcomes and immune microenvironment: A silico analysis with in vivo and vitro validation
Authors: Chen Xu , Yuan Qihang , Liu Jifeng , Xia Shilin , Shi Xueying , Su Yuxin , Wang Zhizhou , Li Shuang , Shang Dong
Published: October 2022

The extracellular matrix (ECM) is a vital component of the tumor microenvironment, which interplays with stromal and tumor cells to stimulate the capacity of cancer cells to proliferate, migrate, invade, and undergo angiogenesis. Nevertheless, the crucial functions of ECM-related genes (ECMGs) in pancreatic adenocarcinoma (PAAD) have not been systematically evaluated. Hence, a comprehensive evaluation of the ECMGs is required in pan-cancer, especially in PAAD. First, a pan-cancer overview of ECMGs was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. Seven ECMGs (i.e. LAMB3, LAMA3, ITGB6, ITGB4, ITGA2, LAMC2, and COL11A1) were identified to be hub genes of PAAD, which were obviously up-regulated in PAAD and considerably linked to tumor stage as well as prognosis. Subsequently, patients with PAAD were divided into 3 clusters premised on ECMG expression and ECM scores. Cluster 2 was the subtype with the best prognosis accompanied by the lowest ECM scores, further verifying ECM’s significant contribution to the pathophysiological processes of PAAD. Significant differences were observed for oncogene and tumor suppressor gene expression, immune microenvironment, and chemotherapy sensitivity across three ECM subtypes. After applying a variety of bioinformatics methods, a novel and robust ECM-associated mRNA-lncRNA-based prognostic panel (ECM-APP) was developed and validated for accurately predicting clinical outcomes of patients with PAAD. Patients with PAAD were randomly categorized into the train, internal validation, and external validation cohorts; meanwhile, each patient was allocated into high-risk (unfavorable prognosis) and low-risk (favorable prognosis) populations premised on the expression traits of ECM-related mRNAs and lncRNAs. The discrepancy in the tumor mutation burden and immune microenvironment might be responsible for the difference in prognoses across the high-risk and low-risk populations. Overall, our findings identified and validated seven ECMGs remarkably linked to the onset and progression of PAAD. ECM-based molecular classification and prognostic panel aid in the prognostic assessment and personalized intervention of patients with PAAD.
Changes towards stable good somatic condition and increased gonad investment of Norwegian spring-spawning herring (Clupea harengus) after 2005 are linked to extended feeding period
Authors: Homrum Eydna í , Óskarsson Guðmundur J. , Ono Kotaro , Hølleland Sondre , Slotte Aril
Published: October 2022

Norwegian spring spawning herring (Clupea harengus) migrate from spawning areas on the Norwegian shelf in February-March to feeding areas in the Norwegian Sea in April-August, returning to wintering areas in northern Norwegian waters from September onwards when feeding ceases. After around 2005 the Norwegian Sea has become warmer and here we address recent changes in migration, somatic condition and gonad development of herring related to these changes. Analyses were based on combined Norwegian, Icelandic and Faroese data on fishery (~81% of total commercial catch) and biological parameters from an extensive material of individual fish (n = 310749) during the period 1994-2019. Fishery data demonstrated large-scale changes in herring distribution over the study period. This was further supported by spatiotemporal modelling of body growth, somatic condition, gonad development and concurrent centre of gravity changes of the sampled fish. After 2005 the population showed a clear tendency of being distributed farther south-westwards in the Norwegian Sea during feeding and returning to wintering areas later in the year. This tendency increased with age, and with body length and somatic condition within age groups. Moreover, the somatic condition increased for all age groups from the early 2000s towards stable high levels after 2005, mainly due to extra weight gained from extended feeding into the autumn. Length at age decreased continuously during 2003-2010 for all age groups, suggesting impact of density dependent limiting factors but also that the environmental shift may have led to immediate poorer feeding conditions early in the year. Hence, extra energy from extended autumn feeding was rather invested into gonad weights tending to increase over the study period. Mechanisms behind the observed changes are likely linked to spatial and seasonal changes in zooplankton abundance. Overall, zooplankton production possibilities along the frontal areas in the south-western part of the Norwegian Sea have likely increased after the general environmental shift. This also includes a change towards increased probabilities of an additional second generation of some copepods developing in warmer waters, facilitating a prolonged feeding period for herring.
The Mediterranean bioconstructor Lithophyllum stictiforme shows adaptability to future warming
Authors: Pinna Federico , Caragnano Annalisa , Piazzi Luigi , Ragazzola Federica , Stipcich Patrizia , Rindi Fabio , Ceccherelli Giulia
Published: October 2022

Understanding how coralline algae may acclimatize to ocean warming is important to understand their survival over the coming century. Taking advantage of natural differences in temperature conditions between coastal areas in Sardinia (Italy) and between depths, the responses in terms of biological traits to warming of the crustose coralline alga Lithophyllum stictiforme, a key bioconstructor of coralligenous reefs in the Mediterranean, were evaluated in the field by two innovative transplant experiments where translocated specimens were used as controls. Results of the first experiment (algae cross transplanted between a cold and a warm site at two depths, 23 and 34 m) showed that the marginal growth of the alga and production of conceptacles were higher in the cold site, regardless of the treatment (transplant and translocation) and depth. However, growth in thickness in algae transferred from the cold to the warm site was higher at 34 m of depth, where they had a better performance than the local (translocated) algae. Results of the second experiment (algae transplanted from 34 m to 15 m of depth under different light irradiance manipulations) evidenced that the increase in temperature of +4°C was tolerated by thalli transplanted at 15 m, but that thallus growth and conceptacles production was negatively affected by the higher light irradiance. These results suggest an overall good adaptability of L. stictiforme under warmer conditions, even those due to thermocline deepening. Overall, these results encourage consideration of the use of transplants of this bioconstructor in future restoration actions of coralligenous habitats.
Freeze–Thaw damage characteristics of composite modified open graded friction course
Authors: Qi Lin , Yu Baoyang , Song Jingang , Zhang Chunshuai
Published: October 2022

To reasonably describe the damage characteristics of composite modified open graded friction course (OGFC) after multiple freeze-thaw cycles, based on the Able viscoelastic constitutive equation, a viscoelastic model of freeze-thaw damage was constructed and analyzed using the Weibull distribution function, damage mechanics, and fractional derivative theory. Under the conditions of composite modified OGFC mixtures with different mixing ratios (12%, 0%), (12%, 1%), and (12%, 2%), and multiple freeze-thaw cycles (0–16), low-temperature bending and creep tests of the mixtures were carried out. The stress-strain curve data obtained were fitted to analyze the physical significance of the model parameters. The results show that the model is suitable for characterizing the viscoelastic stage of composite modified OGFC under 10 freeze-thaw cycles. The freeze-thaw damage model parameters of three types of composite modified OGFC with different mixing ratios were compared and analyzed. The order of the fractional derivative of the composite modified OGFC model (12%, 1%) was 0.2223, the maximum damage threshold was 1.108, and the maximum viscosity coefficient was 371.84. This composite modified OGFC had the best low-temperature crack resistance.
Multi-frame DVC for temporal image sequences
Authors: Manigrasso Zaira , Goethals Wannes , Goudarzi Niloofar M. , Boone Matthieu N. , Samaro Aseel , Vervaet Chris , Philips Wilfried , Aelterman Jan
Published: October 2022

Digital volume correlation (DVC) is a 3D image-based technique for displacement and strain computation. Traditionally, both (digital image correlation) DIC and DVC are methods based on two individual time frames; the estimation of the displacement and strain field is done using one reference and one moving frame as input. However, dynamic experiments generate more than two temporal frames. Therefore, with classical DVC techniques, only a subset of the available data is used. In this study, we propose a novel DVC method that can rely on more than two frames for the displacement and strain computation. The proposed method aims to be as general as possible; there is no constraint regarding the nature or the rate of the displacement (e.g., cyclic or linear). The aim of this method is to impose a temporal regularization that improves the self-consistency of the algorithm. The multi-frame DVC improves the quality of the registration in challenging situations. As an example, we investigate the dissolution of a pharmaceutical tablet in water, which undergoes three processes: swelling, gel formation, and material erosion. The accuracy of the registration—quantified by the sum of square differences (SSD)—has improved by 23% on an average with respect to the classical two-frame method. Classical DVC methods fail in registering images with structures that change appearance through time, such as the tablet that, in contact with water, reacts chemically, changing phase and becoming a gel. Moreover, we proved that multi-frame DVC is more robust in registering images with severe but realistic motion artefacts. As an example for this case, we apply the method to a series of μ-CT datasets of aluminum foam during a compression experiment. As seen with the tablets, we are in a situation where the appearance of the structures in the images changes through time, but in this case it is because of motion artefacts. Finally, the use of more than two frames makes the method more robust against noisy images, with an average improvement of 35% in registration accuracy obtained using the three-frame DVC method compared to the classical two-frame DVC method.
Effect of chronic lung diseases on mortality of prevariant COVID-19 pneumonia patients
Authors: Kilic Hatice , Arguder Emine , Karalezli Aysegul , Unsal Ebru , Guner Rahmet , Kayaslan Bircan , Hasanoglu İmran , Ates İhsan , Civak Musa , Akpınar Esmehan , Parlak Ebru , Sadi Filiz , Kocaman Yasin , Günay Sibel , Metan Esra , Er Mukremin , Dalkıran Aynil , Hezer Habibe , Ergüden Hülya , Hancıoğlu Zeynep , Kalem Ayşe , Eser Fatma , Aypak Adalet , Akıncı Esragül , Karahmetoğlu Selma , Gemcioglu Emin , Kalkan Emra , İnan Osman , Yilmaz Abdulrezzak , Güler Bagdagul , Çopuroğlu Esra , Turan İşil , Gökmen Derya , Hayme Serhat , Surel Aziz Ahmet
Published: October 2022

Background

The aim of the study is to assess the effect of chronic lung disease on mortality in patients hospitalized with the diagnosis of prevariant COVID-19 Pneumonia compared to patients without chronic lung disease.

Research design and methods

A cohort of 1,549 patients admitted to the pandemic clinic with a COVID-19 Pneumonia diagnosis was analyzed. Group 1 and Group 2 were compared in terms of the treatment they received, admission to intensive care, mortality and follow-up parameters.

Results

The patient group with COVID-19 and lung disease consisted of 231 participants (14.91%) (Group 1). The patient group with COVID-19 but without lung disease had 1,318 participants (85.19%). Group 1 cases were found to receive more oxygen therapy and mechanical ventilation than Group 2 cases (p ≤ 0.001), Following univariate and multiple logistic regression analyses, it was determined that patients with chronic lung disease had a 25.76% higher mortality risk [OR: 25.763, 95% CI (Lower-Upper) (2.445–271.465), p = 0.007].

Conclusion

It was found that chronic lung disease contributed significantly to mortality in this study. Among chronic lung diseases, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and interstitial lung diseases (ILDs) were shown to be more effective than other chronic lung diseases in patients with prevariant COVİD-19 population.
Comparative analysis of Vibrio cholerae isolates from Ghana reveals variations in genome architecture and adaptation of outbreak and environmental strains
Authors: Adade Nana Eghele , Aniweh Yaw , Mosi Lydia , Valvano Miguel A. , Duodu Samuel , Ahator Stephen Dela
Published: October 2022

Recurrent epidemics of cholera denote robust adaptive mechanisms of Vibrio cholerae for ecological shifting and persistence despite variable stress conditions. Tracking the evolution of pathobiological traits requires comparative genomic studies of isolates from endemic areas. Here, we investigated the genetic differentiation among V. cholerae clinical and environmental isolates by highlighting the genomic divergence associated with gene decay, genome plasticity, and the acquisition of virulence and adaptive traits. The clinical isolates showed high phylogenetic relatedness due to a higher frequency of shared orthologs and fewer gene variants in contrast to the evolutionarily divergent environmental strains. Divergence of the environmental isolates is linked to extensive genomic rearrangements in regions containing mobile genetic elements resulting in numerous breakpoints, relocations, and insertions coupled with the loss of virulence determinants acf, zot, tcp, and ctx in the genomic islands. Also, four isolates possessed the CRISPR-Cas systems with spacers specific for Vibrio phages and plasmids. Genome synteny and homology analysis of the CRISPR-Cas systems suggest horizontal acquisition. The marked differences in the distribution of other phage and plasmid defense systems such as Zorya, DdmABC, DdmDE, and type-I Restriction Modification systems among the isolates indicated a higher propensity for plasmid or phage disseminated traits in the environmental isolates. Our results reveal that V. cholerae strains undergo extensive genomic rearrangements coupled with gene acquisition, reflecting their adaptation during ecological shifts and pathogenicity.
Pre- and postsynaptic alterations in the visual cortex of the P23H-1 retinal degeneration rat model
Authors: Martinez-Galan Juan R. , Garcia-Belando Maria , Cabanes-Sanchis Jose J. , Caminos Elena
Published: October 2022

P23H rats express a variant of rhodopsin with a mutation that leads to loss of visual function with similar properties as human autosomal dominant retinitis pigmentosa (RP). The advances made in different therapeutic strategies to recover visual system functionality reveal the need to know whether progressive retina degeneration affects the visual cortex structure. Here we are interested in detecting cortical alterations in young rats with moderate retinal degeneration, and in adulthood when degeneration is severer. For this purpose, we studied the synaptic architecture of the primary visual cortex (V1) by analyzing a series of pre- and postsynaptic elements related to excitatory glutamatergic transmission. Visual cortices from control Sprague Dawley (SD) and P23H rats at postnatal days 30 (P30) and P230 were used to evaluate the distribution of vesicular glutamate transporters VGLUT1 and VGLUT2 by immunofluorescence, and to analyze the expression of postsynaptic density protein-95 (PSD-95) by Western blot. The amount and dendritic spine distribution along the apical shafts of the layer V pyramidal neurons, stained by the Golgi-Cox method, were also studied. We observed that at P30, RP does not significantly affect any of the studied markers and structures, which suggests in young P23H rats that visual cortex connectivity seems preserved. However, in adult rats, although VGLUT1 immunoreactivity and PSD-95 expression were similar between both groups, a narrower and stronger VGLUT2-immunoreactive band in layer IV was observed in the P23H rats. Furthermore, RP significantly decreased the density of dendritic spines and altered their distribution along the apical shafts of pyramidal neurons, which remained in a more immature state compared to the P230 SD rats. Our results indicate that the most notable changes in the visual cortex structure take place after a prolonged retinal degeneration period that affected the presynaptic thalamocortical VGLUT2-immunoreactive terminals and postsynaptic dendritic spines from layer V pyramidal cells. Although plasticity is more limited at these ages, future studies will determine how reversible these changes are and to what extent they can affect the visual system’s functionality.
Contribution of cognitive and bodily navigation cues to egocentric and allocentric spatial memory in hallucinations due to Parkinson's disease: A case report
Authors: Tuena Cosimo , Riva Giuseppe , Murru Immacolata , Campana Luca , Goulene Karine M. , Pedroli Elisa , Stramba-Badiale Marco
Published: October 2022

Parkinson's disease (PD) manifestations can include visual hallucinations and illusions. Recent findings suggest that the coherent integration of bodily information within an egocentric representation could play a crucial role in these phenomena. Egocentric processing is a key aspect of spatial navigation and is supported by the striatum. Due to the deterioration of the striatal and motor systems, PD mainly impairs the egocentric rather than the allocentric spatial frame of reference. However, it is still unclear the interplay between spatial cognition and PD hallucinations and how different navigation mechanisms can influence such spatial frames of reference. We report the case of A.A., a patient that suffers from PD with frequent episodes of visual hallucinations and illusions. We used a virtual reality (VR) navigation task to assess egocentric and allocentric spatial memory under five navigation conditions (passive, immersive, map, path decision, and attentive cues) in A.A. and a PD control group without psychosis. In general, A.A. exhibited a statistically significant classical dissociation between the egocentric and allocentric performance with a greater deficit for the former. In particular, the dissociation was statistically significant in the “passive” and “attentive cues” conditions. Interestingly in the “immersive” condition, the dissociation was not significant and, in contrast to the other conditions, trends showed better performance for egocentric than allocentric memory. Within the theories of embodiment, we suggest that body-based information, as assessed with VR navigation tasks, could play an important role in PD hallucinations. In addition, the possible neural underpinnings and the usefulness of VR are discussed.
Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics
Authors: Valihrach Lukas , Matusova Zuzana , Zucha Daniel , Klassen Ruslan , Benesova Sarka , Abaffy Pavel , Kubista Mikael , Anderova Miroslava
Published: October 2022

Oligodendrocytes (OL) have been for decades considered a passive, homogenous population of cells that provide support to neurons, and show a limited response to pathological stimuli. This view has been dramatically changed by the introduction of powerful transcriptomic methods that have uncovered a broad spectrum of OL populations that co-exist within the healthy central nervous system (CNS) and also across a variety of diseases. Specifically, single-cell and single-nucleus RNA-sequencing (scRNA-seq, snRNA-seq) have been used to reveal OL variations in maturation, myelination and immune status. The newly discovered immunomodulatory role suggests that OL may serve as targets for future therapies. In this review, we summarize the current understanding of OL heterogeneity in mammalian CNS as revealed by scRNA-seq and snRNA-seq. We provide a list of key studies that identify consensus marker genes defining the currently known OL populations. This resource can be used to standardize analysis of OL related datasets and improve their interpretation, ultimately leading to a better understanding of OL functions in health and disease.
Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice
Authors: Nicolicht-Amorim Priscila , Delgado-Garcia Lina M. , Nakamura Thabatta Karollynne Estevam , Courbassier Natália Rodrigues , Mosini Amanda Cristina , Porcionatto Marimelia A.
Published: October 2022

The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood–brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen–glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.
Altered stability of brain functional architecture after sleep deprivation: A resting-state functional magnetic resonance imaging study
Authors: Huang Nao-Xin , Gao Zhu-Ling , Lin Jia-Hui , Lin Yan-Juan , Chen Hua-Jun
Published: October 2022

Background and aims

Resting-state functional magnetic resonance imaging (fMRI) studies using static and dynamic functional connectivity (FC) approaches have revealed brain dysfunction resulting from sleep deprivation (SD). The effects of SD on the stability of brain functional architecture remain unclear. This study investigated the functional stability (FS) changes induced by SD and its association with neurocognitive alterations.

Materials and methods

In this study, we recruited 24 healthy women. All participants underwent two sessions of resting-state fMRI scanning and neurocognitive assessment. The assessments included the Digit Symbol Test, Digit Span Test, Trail-Making Test (TMT), and Complex Figure Test (CFT). Participants completed one session under rested wakefulness (RW) and one session after SD for 24 h. To estimate dynamic FC, we used the sliding window approach; and then, to characterize the FS of each voxel, we measured dynamic FC concordance over time. We used a paired t-test to identify differences in FS between RW and SD. To examine the relationship between these changes in FS and alterations in neurocognitive performance, we conducted Spearman’s correlation analyses.

Results

SD affected the performance of the Digit Symbol Test, Digit Span Test, and CFT. Compared with RW, subjects with SD exhibited decreased FS in the bilateral anterior and posterior cingulate gyrus and medial frontal gyrus, right superior frontal gyrus, and cerebellum posterior lobe, while they exhibited increased FS in the bilateral precentral/postcentral gyrus and supplementary motor area, right parahippocampal gyrus and fusiform gyrus, left inferior occipital gyrus, and bilateral cerebellum anterior lobe. After SD, FS changes in the right parahippocampal gyrus and fusiform gyrus were correlated with altered performance in the Digit Symbol Test and CFT.

Conclusion

Our findings showed that the stability of the brain’s functional architecture could be altered by SD. This stability alteration may correspond to multiple neurocognitive domain changes.
Involvement of the cerebellum in migraine
Authors: Wang Mengya , Tutt Joseph O. , Dorricott Nicholas O. , Parker Krystal L. , Russo Andrew F. , Sowers Levi P.
Published: October 2022

Migraine is a disabling neurological disease characterized by moderate or severe headaches and accompanied by sensory abnormalities, e.g., photophobia, allodynia, and vertigo. It affects approximately 15% of people worldwide. Despite advancements in current migraine therapeutics, mechanisms underlying migraine remain elusive. Within the central nervous system, studies have hinted that the cerebellum may play an important sensory integrative role in migraine. More specifically, the cerebellum has been proposed to modulate pain processing, and imaging studies have revealed cerebellar alterations in migraine patients. This review aims to summarize the clinical and preclinical studies that link the cerebellum to migraine. We will first discuss cerebellar roles in pain modulation, including cerebellar neuronal connections with pain-related brain regions. Next, we will review cerebellar symptoms and cerebellar imaging data in migraine patients. Lastly, we will highlight the possible roles of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine symptoms, including preclinical cerebellar studies in animal models of migraine.
Effects of a 12-week whole-grain or refined wheat intervention on plasma acylcarnitines, bile acids and signaling lipids, and association with liver fat: A post-hoc metabolomics study of a randomized controlled trial
Authors: Gijbels Anouk , Schutte Sophie , Esser Diederik , Wopereis Suzan , Gonzales Gerard Bryan , Afman Lydia A.
Published: October 2022

Background

We previously showed that whole-grain wheat (WGW) consumption had beneficial effects on liver fat accumulation, as compared to refined wheat (RW). The mechanisms underlying these effects remain unclear.

Objective

In this study, we investigated the effects of WGW vs. RW consumption on plasma metabolite levels to explore potential underlying mechanisms of the preventive effect of WGW consumption on liver fat accumulation.

Methods

Targeted metabolomics of plasma obtained from a concluded 12-week double-blind, randomized controlled trial was performed. Fifty overweight or obese men and women aged 45–70 years with mildly elevated levels of plasma cholesterol were randomized to either 98 g/d of WGW or RW products. Before and after the intervention, a total of 89 fasting plasma metabolite concentrations including acylcarnitines, trimethylamine-N-oxide (TMAO), choline, betaine, bile acids, and signaling lipids were quantified by UPLC-MS/MS. Intrahepatic triglycerides (IHTG) were quantified by 1H-MRS, and multiple liver markers, including circulating levels of β-hydroxybutyrate, alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (γ-GT), serum amyloid A (SAA), and C-reactive protein, were assessed.

Results

The WGW intervention increased plasma concentrations of four out of 52 signaling lipids—lysophosphatidic acid C18:2, lysophosphatidylethanolamine C18:1 and C18:2, and platelet-activating factor C18:2—and decreased concentrations of the signaling lipid lysophosphatidylglycerol C20:3 as compared to RW intervention, although these results were no longer statistically significant after false discovery rate (FDR) correction. Plasma concentrations of the other metabolites that we quantified were not affected by WGW or RW intervention. Changes in the above-mentioned metabolites were not correlated to change in IHTG upon the intervention.

Conclusion

Plasma acylcarnitines, bile acids, and signaling lipids were not robustly affected by the WGW or RW interventions, which makes them less likely candidates to be directly involved in the mechanisms that underlie the protective effect of WGW consumption or detrimental effect of RW consumption on liver fat accumulation.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [NCT02385149].
A review of the biology and therapeutic implications of cancer-associated fibroblasts (CAFs) in muscle-invasive bladder cancer
Authors: Burley Amy , Rullan Antonio , Wilkins Anna
Published: October 2022

Cancer-associated fibroblasts (CAFs) play a fundamental role in the development of cancers and their response to therapy. In recent years, CAFs have returned to the spotlight as researchers work to unpick the mechanisms by which they impact tumour evolution and therapy responses. However, study of CAFs has largely been restricted to a select number of common cancers, whereas research into CAF biology in bladder cancer has been relatively neglected. In this review, we explore the basics of CAF biology including the numerous potential cellular origins of CAFs, alongside mechanisms of CAF activation and their diverse functionality. We find CAFs play an important role in the progression of bladder cancer with significant implications on tumour cell signaling, epithelial to mesenchymal transition and the capacity to modify components of the immune system. In addition, we highlight some of the landmark papers describing CAF heterogeneity and find trends in the literature to suggest that the iCAF and myCAF subtypes defined in bladder cancer share common characteristics with CAF subtypes described in other settings such as breast and pancreatic cancer. Moreover, based on findings in other common cancers we identify key therapeutic challenges associated with CAFs, such as the lack of specific CAF markers, the paucity of research into bladder-specific CAFs and their relationship with therapies such as radiotherapy. Of relevance, we describe a variety of strategies used to target CAFs in several common cancers, paying particular attention to TGFβ signaling as a prominent regulator of CAF activation. In doing so, we find parallels with bladder cancer that suggest CAF targeting may advance therapeutic options in this setting and improve the current poor survival outcomes in bladder cancer which sadly remain largely unchanged over recent decades.
Peripheral absolute eosinophil count identifies the risk of serious immune-related adverse events in non-small cell lung cancer
Authors: Wu Yan , Li Dapeng , Wu Mengyao , Yang Ying , Shen Meng , Chen Kai
Published: October 2022

Background

Immune-related adverse events (irAEs) have drawn a lot of attention lately as a result of the predominance of immunotherapy in advanced non-small cell lung cancer (NSCLC). However, the clinical evidence for irAEs in real life is limited. In this paper, the occurrence of irAEs in Chinese NSCLC patients was examined, and possible risk factors for the emergence of severe irAEs were discovered.

Methods

Our retrospective investigation assessed the occurrence of adverse events (AEs) and prognosis of 213 patients who received immunotherapy for NSCLC. Using univariate and multivariate logistic regression models, the association between clinicopathological traits and the incidence of severe irAEs was investigated. To assess the prognostic impact of irAEs, survival data was analyzed.

Results

Among the 213 NSCLC patients, 122 (57.3%) had irAEs of any grade, and 38 (17.8%) had high-grade (grade 3-5) AEs. Baseline peripheral absolute eosinophil count (AEC) (HR 6.58, 95% CI: 1.5-28.8, P=0.012) was found to be an independent predictor of high-grade irAEs by multivariate analysis. The survival analysis revealed that patients with severe irAEs had worse OS (15.7 vs. 20.8 months, 95% CI: 11.6-19.8 vs. 16.0-25.5, P=0.026).

Conclusion

According to our findings, the peripheral absolute eosinophil count (AEC) is a reliable indicator of severe irAEs in NSCLC. Serious irAEs that occur in patients often reflect poor prognoses. In the future, high-grade irAEs should receive more attention.
MARCH1 as a novel immune-related prognostic biomarker that shapes an inflamed tumor microenvironment in lung adenocarcinoma
Authors: Xu Zhiyong , Liu Jun , Liu Zichuan , Zhang Haibo
Published: October 2022

E3 ubiquitin ligases (E3s), the second most common cancer-related functional protein family, play vital roles in multiple tumors. However, their importance in prognosis and immunotherapy of lung adenocarcinoma (LUAD) is not clear. First, utilizing the data from The Cancer Genome Atlas (TCGA), we comprehensively assessed the expression profile and immunological association of 13 E3s in LUAD patients. Consequently, MARCH1 was considered a candidate for further study. Second, several algorithms were applied to assess the correlation between MARCH1 and immunological characteristics in the LUAD tumor microenvironment. Third, an immune risk score (IRS) was developed to predict the prognosis. Finally, the immunological relationship of MARCH1 in pan-cancer was also estimated. We found that E3s were disordered in LUAD. Among them, MARCH1 was positively correlated with most immunological characteristics, indicating that MARCH1 designed an inflamed TME in LUAD. Coincidently, LUAD with low MARCH1 expression had a poor prognosis and was not sensitive to immune checkpoint blockers. In addition, the IRS could accurately predict the prognosis. In pan-cancer, MARCH1 was also positively correlated with most immunological characteristics. In conclusion, MARCH1 could be a novel and promising biomarker for immune status and effectiveness of immunotherapy for LUAD patients.
The role of lncRNAs in regulation of DKD and diabetes-related cancer
Authors: Cheng Yawei , Wu Xiaowen , Xia Yujie , Liu Wenjun , Wang Peter
Published: October 2022

Diabetes mellitus often results in several complications, such as diabetic kidney disease (DKD) and end-stage renal diseases (ESRDs). Cancer patients often have the dysregulated glucose metabolism. Abnormal glucose metabolism can enhance the tumor malignant progression. Recently, lncRNAs have been reported to regulate the key proteins and signaling pathways in DKD development and progression and in cancer patients with diabetes. In this review article, we elaborate the evidence to support the function of lncRNAs in development of DKD and diabetes-associated cancer. Moreover, we envisage that lncRNAs could be diagnosis and prognosis biomarkers for DKD and cancer patients with diabetes. Furthermore, we delineated that targeting lncRNAs might be an alternative approach for treating DKD and cancer with dysregulated glucose metabolism.
Combined clinical features and MRI parameters for the prediction of VEGFR2 in hepatocellular carcinoma patients
Authors: Zhang Laizhu , Cheng Chunxiao , Li Binghua , Chen Jun , Peng Jin , Cao Yajuan , Yue Yang , Mai Xiaoli , Yu Decai
Published: October 2022

Purpose

To develop a prediction model for estimating the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in hepatocellular carcinoma (HCC) patients using clinical features and the contrast-enhanced MRI Liver Imaging Reporting and Data System (LI-RADS).

Methods

A total of 206 HCC patients were subjected to preoperative contrast-enhanced MRI, radical resection, and VEGFR2 immunohistochemistry labeling. The intensity of VEGFR2 expression was used to split patients into either the positive group or the negative group. For continuous data, the Mann-Whitney U test was employed, and for categorical variables, the χ2 test was utilized.

Results

VEGFR2-positivity was identified in 41.7% (86/206) of the patients. VEGFR2-positive HCCs were confirmed by higher serum alpha-fetoprotein (AFP) levels, larger tumor dimensions (either on MRI or upon final pathology), and a higher LI-RADS score (all p < 0.001). LI-RADS scores and AFP levels were independent predictors for high VEGFR2 expression. These two parameters were used to establish a VEGFR2-positive risk nomogram, which was validated to possess both good discrimination and calibration. The area under the curve was 0.830 (sensitivity 83.6%, specificity 72.5%) and the mean absolute error was 0.021. The threshold probabilities ranged between 0.07 and 0.95, and usage of the model contributed net benefits.

Conclusion

A nomogram including clinical features and contrast-enhanced MRI parameters was developed and was demonstrably effective at predicting VEGFR2 expression in HCC patients.
Screening of possible biomarkers and therapeutic targets in kidney renal clear cell carcinoma: Evidence from bioinformatic analysis
Authors: Peng Longfei , Cao Zhangjun , Wang Qi , Fang Lu , Yan Songbai , Xia Dian , Wang Jinyou , Bi Liangkuan
Published: October 2022

Renal cell carcinoma (RCC), as one of the most common urological malignancies, has many histologic and molecular subtypes, among which clear cell renal cell carcinoma (ccRCC) is one of the most common causes of tumor-related deaths. However, the molecular mechanism of ccRCC remains unclear. In order to identify the candidate genes that may exist in the occurrence and development of ccRCC, microarray datasets GSE6344, GSE16441, GSE36895, GSE53757 and GSE76351 had been downloaded from Gene Expression Omnibus (GEO) database. Apart from that, the differentially expressed genes (DEGs) were screened through Bioinformatics & Evolutionary Genomics. In addition, the protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. By virtue of DAVID online database, GO/KEGG enrichment analysis of DEGs was performed. Consequently, a total of 118 DEGs were screened, including 24 up-regulated genes and 94 down-regulated genes. The plug-in MCODE of Cytoscape was adopted to analyze the most significant modules of DEGs. What’s more, the genes with degree greater than 10 in DEGs were selected as the hub genes. The overall survival (OS) and disease progression free survival (DFS) of 9 hub genes were analyzed through GEPIA2 online platform. As shown by the survival analysis, SLC34A1, SLC12A3, SLC12A1, PLG, and ENO2 were closely related to the OS of ccRCC, whereas SLC34A1 and LOX were closely related to DFS. Among 11 SLC members, 6 SLC members were highly expressed in non-cancerous tissues (SLC5A2, SLC12A1, SLC12A3, SLC34A1, SLC34A2, SLC34A3). Besides, SLC12A5 and SLC12A7 were highly expressed in ccRCC. Furthermore, SLC12A1-A7, SLC34A1 and SLC34A3 were closely related to OS, whereas SLC12A2/A4/A6/A7 and SLC34A1/A3 were closely related to DFS. In addition, 5 algorithms were used to analyze hub genes, the overlapping genes were AQP2 and KCNJ1. To sum up, hub gene can help us understand the molecular mechanism of the occurrence and development of ccRCC, thereby providing a theoretical basis for the diagnosis and targeted therapy of ccRCC.
Role of diffusion-weighted MRI in differentiation between benign and malignant anterior mediastinal masses
Authors: Thuy Tran Thi Mai , Trang Nguyen Truong Hoang , Vy Tran Thanh , Duc Vo Tan , Nam Nguyen Hoang , Chien Phan Cong , Nhi Le Huu Hanh , Minh Le Huu Nhat
Published: October 2022

Diffusion-weighted imaging (DWI) is considered to be a useful biomarker to characterize the cellularity of lesions, yet its application in the thorax to evaluate anterior mediastinal lesions has not been well investigated. The aims of our study were to describe the magnetic resonance (MR) characteristics of anterior mediastinal masses and to assess the role of apparent diffusion coefficient (ADC) value in distinguishing benign from malignant lesions of the anterior mediastinum. We conducted a retrospective cross-sectional study including 55 patients with anterior mediastinal masses who underwent preinterventional MR scanning with the following sequences: T1 VIBE DIXON pre and post-contrast, T2 HASTE, T2 TIRM, DWI-ADC map (b values of 0 and 2000 sec/mm2). The ADC measurements were obtained by two approaches: hot-spot ROI and whole-tumor histogram analysis. The lesions were grouped by three distinct ways: benign versus malignant, group A (benign lesions and type A, AB, B1 thymoma) versus group B (type B2, B3 thymoma and other malignant lesions), lymphoma versus other malignancies. The study was composed of 55 patients, with 5 benign lesions and 50 malignant lesions. The ADCmean, ADCmedian, ADC10, ADC90 in the histogram-based approach and the hot-spot-ROI-based mean ADC of the malignant lesions were significantly lower than those of benign lesions (P values< 0.05). The hot-spot-ROI-based mean ADC had the highest value in differentiation between benign and malignant mediastinal lesions, as well as between group A and group B; the ADC cutoffs (with sensitivity, specificity) to differentiate malignant from benign lesions and group A from group B were 1.17 x 10-3 mm2/sec (80%, 80%) and 0.99 x 10-3 mm2/sec (78.4%, 88.9%), respectively. The ADC values obtained by using the hot-spot-ROI-based and the histogram-based approaches are helpful in differentiating benign and malignant anterior mediastinal masses.
A concise pathophysiological model of acute appendicitis against the background of the COVID-19 pandemic
Authors: Reismann Marc
Published: October 2022

One of the most common clinical pictures has become the focus of attention during the COVID-19 pandemic: acute appendicitis with the associated diagnostics and therapy. The aim of the work is to show inconsistencies with regard to epidemiology, pathophysiology and therapy against the background of the pandemic with special attention to the conditions for children and to explain the pathophysiological processes that are likely to underlie the disease based on scientifically plausible models.
Increased efficacy of dietary supplement containing wax ester-rich marine oil and xanthophylls in a mouse model of dry macular degeneration
Authors: Melecchi Alberto , Amato Rosario , Lapi Dominga , Dal Monte Massimo , Rusciano Dario , Bagnoli Paola , Cammalleri Maurizio
Published: October 2022

Age-related macular degeneration (AMD) is nowadays considered among the retinal diseases whose clinical management lacks established treatment approaches, mainly for its atrophic (dry) form. In this respect, the use of dietary patterns enriched in omega-3 and antioxidant xanthophylls has emerged as a promising approach to counteract dry AMD progression although the prophylactic potential of omega-3 of fish origin has been discussed. Whether enriched availability of omega-3 and xanthophylls may increase the effectiveness of diet supplementation in preventing dry AMD remains to be fully established. The present study aims at comparing the efficacy of an existing orally administered formulation based on lutein and fish oil, as a source of omega-3, with a novel formulation providing the combination of lutein and astaxanthin with Calanus oil (COil), which contains omega-3 together with their precursors policosanols. Using a mouse model of dry AMD based on subretinal injection of polyethylene glycol (PEG)-400, we assessed the comparative efficacy of both formulations on PEG-induced major hallmarks including oxidative stress, inflammation, glial reactivity and outer retinal thickness. Dietary supplementation with both mixtures has been found to exert a significant antioxidant and anti-inflammatory activity as reflected by the overall amelioration of the PEG-induced pathological hallmarks. Noteworthy, the formulation based on COil appeared to be more protective than the one based on fish oil, presumably because of the higher bioavailability of omega-3 in COil. These results support the use of dietary supplements combining omega-3 and xanthophylls in the prevention and treatment of AMD and suggest that the source of omega-3 might contribute to treatment efficacy.
Shear induced diffusion of platelets revisited
Authors: Kotsalos Christos , Raynaud Franck , Lätt Jonas , Dutta Ritabrata , Dubois Frank , Zouaoui Boudjeltia Karim , Chopard Bastien
Published: October 2022

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory.