bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐125a‐3p regulates the expression of FSTL1, a pro‐inflammatory factor, during adipogenic differentiation, and inhibits adipogenesis in mice
Authors: Liu Haifeng , Wen Jie , Tian Xue , Li Tong , Zhao Ju , Cheng Jingjing , Huang Lishi , Zhao Ye , Cao Quanquan , Jiang Jun 
Published: August 2023

AbstractAdipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low‐grade chronic inflammatory disease. Follistatin‐like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain‐ and loss‐of‐function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro‐inflammatory factors IL‐1β and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR‐125a‐3p targeted the 3′ UTR region of FSTL1. These results demonstrated that miR‐125a‐3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR‐125a‐3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL‐1β and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR‐125a‐3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte‐induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR‐125a‐3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity‐related inflammatory diseases.
Frizzled‐9 triggers actin polymerization and activates mechano‐transducer YAP to rescue simulated microgravity‐induced osteoblast dysfunction
Authors: Shi Qiusheng , Gui Jinpeng , Sun Lianwen , Song Yaxin , Na Jing , Zhang Jingyi , Fan Yubo , Zheng Lisha 
Published: August 2023

AbstractLong‐term spaceflight can result in bone loss and osteoblast dysfunction. Frizzled‐9 (Fzd9) is a Wnt receptor of the frizzled family that is vital for osteoblast differentiation and bone formation. In the present study, we elucidated whether Fzd9 plays a role in osteoblast dysfunction induced by simulated microgravity (SMG). After 1–7 days of SMG, osteogenic markers such as alkaline phosphatase (ALP), osteopontin (OPN), and Runt‐related transcription factor 2 (RUNX2) were decreased, accompanied by a decrease in Fzd9 expression. Furthermore, Fzd9 expression decreased in the rat femur after 3 weeks of hindlimb unloading. In contrast, Fzd9 overexpression counteracted the decrease in ALP, OPN, and RUNX2 induced by SMG in osteoblasts. Moreover, SMG regulated phosphorylated glycogen synthase kinase‐3β (pGSK3β) and β‐catenin expression or sublocalization. However, Fzd9 overexpression did not affect pGSK3β and β‐catenin expression or sublocalization induced by SMG. In addition, Fzd9 overexpression regulated protein kinase B also known as Akt and extracellular signal‐regulated kinase (ERK) phosphorylation and induced F‐actin polymerization to form the actin cap, press the nuclei, and increase nuclear pore size, thereby promoting the nuclear translocation of Yes‐associated protein (YAP). Our study findings provide mechanistic insights into the role of Fzd9 in triggering actin polymerization and activating YAP to rescue SMG‐induced osteoblast dysfunction and suggest that Fzd9 is a potential target to restore osteoblast function in individuals with bone diseases and after spaceflight.
Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis
Authors: Li Yan , Liang Xueyan , Li Huijuan , Chen Xiaoyu 
Published: August 2023

Abstract

Background:
Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer (NSCLC); however, evidence regarding their relative efficacy and safety is lacking. This study compared the efficacy and safety of all currently available ICI treatments in patients with advanced NSCLC to identify optimal treatment regimens.

Methods:
PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases were systematically searched for randomized controlled trials (RCTs) published up to August 8, 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR) and adverse events (AEs).

Results:
Forty RCTs involving 22,526 patients were selected, and a total of 26 treatment regimens were identified. Treatment with anti-programmed cell death protein-1 (anti-PD-1) provided superior OS compared with anti-programmed death ligand 1 (anti-PD-L1) treatment. ICIs plus platinum-based chemotherapy (PBC) were superior to ICIs treatment alone, although the addition of PBC increased treatment toxicity. Cemiplimab ranked first for OS and lowest for any-grade AEs in advanced NSCLC patients without PD-L1 selection. Regarding grade ≥3 AEs, the toxicity of ICI monotherapy or ICI–ICI combination was consistently lower than that of the other treatments. For patients without PD-L1 selection, cemiplimab showed the best OS, pembrolizumab plus docetaxel (Pem-DXT) showed the best PFS, and atezolizumab plus bevacizumab and PBC (Atezo-Beva-PBC) showed the best ORR. Pembrolizumab plus PBC and Atezo-Beva-PBC were the most likely optimal treatments for OS and PFS in patients with PD-L1 expression <1%, respectively. In patients with PD-L1 expression ≥1%, treatment regimens containing anti-PD-1 provided superior OS benefits compared with those of anti-PD-L1 treatment, and sintilimab plus PBC (Sint-PBC) provided the best OS benefit; as for PFS, ICI plus PBC consistently showed greater PFS benefits than ICI or PBC alone. For patients with anti-PD-L1 expression of 1–49%, camrelizumab plus PBC provided the best benefit for OS and PFS among included treatment. Durvalumab-tremelimumab-PBC and Atezo-Beva-PBC respectively presented the highest OS and PFS for patients with PD-L1 expression ≥50%. Moreover, cemiplimab and Atezo-Beva-PBC yielded the best OS and PFS benefits as first-line treatments for patients with advanced NSCLC, respectively.

Conclusions:
Although ICI plus PBC likely resulted in superior survival outcomes compared to ICI treatment alone, it did increase toxicity. Cemiplimab presented a well-balanced efficacy and safety profile in advanced NSCLC treatment. Our findings with the current ICIs comparisons will aid future trials for cancer immunotherapy.

Registration:
PROSPERO, https://www.crd.york.ac.uk/PROSPERO/, CRD42022323879.
Provision of chaplaincy services in U.S. hospitals
Authors: White Kelsey B. , Lee Shoou-Yih Daniel , Jennings J’Aime C. , Karimi Seyed , Johnson Christopher E. , Fitchett George 
Published: August 2023

Background
Increasingly, hospitals are expected to provide patient-centered care that attends to patients’ health needs, including spiritual care needs. Chaplaincy services help to meet patients’ spiritual care needs, which have been shown to have a positive impact on health outcomes. Variation in the provision of chaplaincy services suggests hospitals do not uniformly conform to the expectation of making chaplaincy services available.

Purpose
The aim of this study was to examine the availability and factors that influence hospitals’ provision of chaplaincy services.

Methodology
Data were combined from the American Hospital Association annual surveys with the Area Health Resource File at the county level from 2010 to 2019. Observations on general, acute-care community hospitals were analyzed (45,384 hospital-year observations) using logistic regression that clustered standard errors at the hospital level.

Results
Hospitals with Joint Commission accreditation, more staffed beds, nonprofit and government ownership, teaching status, one or more intensive care units, a higher percentage of Medicare inpatient days, church affiliation, and system membership were more likely to provide chaplaincy services than their counterparts. Certification as a trauma hospital and market competition showed no influence on the provision of chaplaincy services.

Conclusion
The lack of chaplaincy services in many hospitals may be due to limited resources, workforce shortage, or a lack of consensus on scope and nature of chaplaincy services.

Practice Implications
Chaplaincy services are an underutilized resource that influences patient experience, clinician burnout and turnover, and the goal of ensuring care is patient-centered. Administrators should consider stronger partnerships where services are provided; researchers and policymakers should consider how the lack of these services in some hospitals may reinforce existing health disparities.
Extracellular vesicles stimulate smooth muscle cell migration by presenting collagen VI
Authors: Kapustin Alexander , Tsakali Sofia Serena , Whitehead Meredith , Chennell George , Wu Meng-Ying , Molenaar Chris , Kutikhin Anton , Bogdanov Leo , Sinitsky Maxim , Rubina Kseniya , Clayton Aled , Verweij Frederik J , Pegtel Dirk Michiel , Zingaro Simona , Lobov Arseniy , Zainullina Bozhana , Owen Dylan , Parsons Maddy , Cheney Richard E. , Warren Derek , Humphries Martin James , Iskratsch Thomas , Holt Mark , Shanahan Catherine M 
Published: August 2023

AbstractThe extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular smooth muscle cells (VSMCs) are essential for vessel repair and, via their secretome, are able to invade from the vessel media into the intima to mediate ECM remodelling. Accumulation of fibronectin (FN) is a hallmark of early vascular repair and atherosclerosis and here we show that FN stimulates VSMCs to secrete small extracellular vesicles (sEVs) by activating the β1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. Spatially, sEV were secreted via filopodia-like cellular protrusions at the leading edge of migrating cells. We found that sEVs are trapped by the ECMin vitroand colocalise with FN in symptomatic atherosclerotic plaquesin vivo. Functionally, ECM-trapped sEVs induced the formation of focal adhesions (FA) with enhanced pulling forces at the cellular periphery. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI.In vitroassays identified collagen VI as playing the key role in cell adhesion and invasion. Taken together our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collage VI enriched sEVs by VSMCs. These sEVs stimulate migration and invasion by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction forces to enable VSMC movement within the complex vascular ECM network.Abstract FigureFigure AbstractVascular smooth muscle cells sense fibronectin via β1 integrin and secrete small extracellular vesicles loaded with collagen VI via filopodia-like protrusions. These extracellular vesicles are entrapped in the extracellular matrix and induce formation of peripheral focal adhesions. Focal adhesions anchor extracellular matrix to the actin fibrils in the cell. Contraction of the actin fibrils generates the mechanical force for cell locomotion and invasion through the matrix. This figure was created with BioRender(https://biorender.com/).
On standardization of controls in lifespan studies
Authors: Spiridonova Olga , Kriukov Dmitrii , Nemirovich-Danchenko Nikolai , Peshkin Leonid 
Published: August 2023

AbstractThe search for interventions to slow down and even reverse aging is a burgeoning field. The literature cites hundreds of supposedly beneficial pharmacological and genetic interventions in model organisms: mice, rats, flies and worms, where research into physiology is routinely accompanied by lifespan data. Naturally the negative results are more frequent, yet scientifically quite valuable if analyzed systematically. Yet, there is a strong “discovery bias”, i.e. results of interventions which turn out not to be beneficial remain unpublished. Theoretically, all lifespan data is ripe for re-analysis: we could contrast the molecular targets and pathways across studies and help focus the further search for interventions. Alas, the results of most longevity studies are difficult to compare. This is in part because there are no clear, universally accepted standards for conducting such experiments or even for reporting such data. The situation is worsened by the fact that the authors often do not describe experimental conditions completely. As a result, works on longevity make up a set of precedents, each of which might be interesting in its own right, yet incoherent and incomparable. Here we point out specific issues and propose solutions for quality control by checking both inter- and intra-study consistency of lifespan data.
Tertiary lymphoid structures are associated with enhanced macrophage activation, immune checkpoint expression and predict outcome in cervical cancer
Authors: Gorvel Laurent , Panouillot Marylou , Rouvière Marie-Sarah , Billon Emilien , Fattori Stéphane , Sonongbua Jumaporn , Boucherit Nicolas , Ben Amara Amira , Quilichini Olivia , Granjeaud Samuel , Degos Clara , Nunes Jacques A. , Carcopino Xavier , Lambaudie Eric , Chretien Anne-Sophie , Sabatier Renaud , Dieu-Nosjean Marie-Caroline , Olive Daniel 
Published: August 2023

AbstractBackgroundCervical tumors are usually treated using surgery, chemotherapy, and radiotherapy, and would benefit from immunotherapies. However, the immune microenvironment in cervical cancer remains poorly described. Tertiary lymphoid structures (TLS) were recently described as markers for better immunotherapy response and overall better prognosis in cancer patients.MethodsWe integratedly evaluated the cervical tumor immune microenvironment, and specifically TLS importance, using combined high-throughput phenotyping, soluble factor dosage, spatial interaction analyses, and statistical analyses.ResultsWe demonstrate that TLS presence is associated with a more inflammatory soluble microenvironment, with the presence of B cells as well as more activated macrophages and dendritic cells (DCs). Furthermore, this myeloid cell activation is associated with expression of immune checkpoints, such as PD-L1 and CD40, and close proximity of activated conventional DC2 to CD8+T cells, therefore indicating better immune interactions and tumor control. Finally, we associate TLS presence, greater B cell density, and activated DC density to improved progression-free survival, and present it as an additional prognostic marker.ConclusionTo conclude, our results provide an exhaustive depiction of the cervical tumor immune microenvironment where TLS presence marks cell activation and immunotherapy target expression. These findings provide predictive clues for patient response to targeted immunotherapies.SignificanceTLS maturation stratifies cervical cancer patients and associates with improved prognosis. TLS associate with the expression of immune checkpoints, notably in the macrophage compartment, which may represent a new therapeutic strategy.
Chrysalis: decoding tissue compartments in spatial transcriptomics with archetypal analysis
Authors: Túrós Demeter , Vasiljevic Jelica , Hahn Kerstin , Rottenberg Sven , Valdeolivas Alberto 
Published: August 2023

AbstractDissecting tissue compartments in spatial transcriptomics (ST) remains challenging due to limited spatial resolution and dependence on single-cell reference data. We present Chrysalis, a novel method to rapidly detect tissue compartments through spatially variable gene (SVG) detection and archetypal analysis without external references. We applied Chrysalis on ST datasets originating from various species, tissues and technologies and demonstrated state-of-the-art performance in identifying cellular niches.
Comparative transcriptome in rhesus macaques and crab-eating macaques
Authors: Mao Yuxiang , Li Yamei , Yang Zikun , Xu Ning , Zhang Shilong , Wang Xuankai , Yang Xiangyu , Sun Qiang , Mao Yafei 
Published: August 2023

AbstractUnderstanding the variations in gene expression between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques and crab-eating macaques serve as crucial nonhuman primate biomedical models with different phenotypes, but the large-scale of comparative transcriptome research between these two species has yet to be fully elucidated. Here, we conduct systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples encompassing 14 common tissues. Our findings reveal that a small fraction of genes (∼3.7%) show differential expression between the two macaque species, while ∼36.5% of genes show tissue-specific expression in both macaques. We also compare gene expression between macaques and humans and ∼22.6 % of the orthologous genes show differential expression in at least 2 tissues. Moreover, ∼19.41% of genes overlapped with macaque-specific structural variants are more likely to show differential expression between humans and macaques. Of these,FAM220Ashows elevated gene expression in humans compared to macaques because of lineage-specific duplication. In summary, our study presents a large-scale analysis of the transcriptomes within macaque species and between macaques and humans. These insights into gene expression variations will enhance the biomedical utility of macaque models and contributing to the broader realm of primate genomic studies.
The effects of skin tone on photoacoustic imaging and oximetry
Authors: Else Thomas R. , Hacker Lina , Gröhl Janek , Bunce Ellie V. , Tao Ran , Bohndiek Sarah E. 
Published: August 2023

ABSTRACTSignificancePhotoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO2). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations.AimTo examine the effects of skin melanin pigmentation on photoacoustic imaging and oximetry.ApproachWe evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealised photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression.ResultsOur computational skin model was consistent with representative literature forin vivoskin reflectance measurements. We observed consistent spectral colouring effects across all model systems, with an overestimation of sO2and more image artefacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO2still suffered from a skin tone-dependent effect.ConclusionPAI demonstrates measurement bias, including an overestimation of blood sO2, in higher Fitzpatrick skin types. Future research should aim to characterise this effect in humans to ensure equitable application of the technology.
Purification, crystallization, and preliminary structural analysis of multivalent immunogenic effector protein-anchored SARS-CoV-2 RBD
Authors: Kwon Taek Hun , Kim Tae Gyun 
Published: August 2023

ABSTRACTThe continuous spread of highly transmissible variants of concern and the potential diminished effectiveness of existing vaccines necessitate ongoing research and development of new vaccines. Immunogenic molecule-anchored antigen has demonstrated superior efficacy in subunit vaccination, primarily due to enhanced cellular uptake facilitated by the affinity between the surface of Immunogenic molecule and the cell membrane. Based on the Immunogenic recombinaseB. malayiRecA (BmRecA), we have overexpressed the construct ofBmRecA with SARS-CoV-2 RBD (BmRecA-RBD) that exists as a stable helical filament formation; it was purified and crystallized to obtain X-ray diffraction data at 2.7 Å, belonged to the hexagonal symmetry groupP65in the unit-cell parameters of a=b=122.12, c=75.55 and α=β=90°, γ=120°. The Matthews coefficient was estimated to be 3.12 Å3Da-1, corresponding to solvent contents of 52.65.
Investigating the Effect of GLU283 Protonation State on the Conformational Heterogeneity of CCR5 by Molecular Dynamics Simulations
Authors: Dogan Berna , Durdagi Serdar 
Published: August 2023

AbstractCCR5 is one of the co-receptors for HIV-1 entry into host cells and is class A GPCR. This receptor has vital roles in the immune system and is involved in the pathogenesis of different diseases. Various studies were conducted to understand its activation mechanism including structural studies in which inactive and active states of the receptor were determined in complex with various binding partners. These determined structures provided opportunities to perform molecular dynamics simulations (MD) and analyze conformational changes observed in protein structures. The atomic level dynamical studies allow us to explore the effects of ionizable residues in the receptor. Here, our aim was to investigate the changes observed in the conformation of CCR5 when it is in complex with inhibitor maraviroc (MRV), an approved anti-HIV drug or HIV-1 envelope protein GP120 in comparison to when the receptor was inapoform. In our simulations, we considered both ionized and protonated states of ionizable binding site residue GLU2837.39in CCR5 as the protonation state of this residue was considered ambiguously in previous studies. Our simulation results suggested that in fact, the change in the protonation state of GLU2837.39caused interaction profiles to be different between CCR5 and its binding partners, GP120 or MRV. We observed that when the protonated state of GLU2837.39was considered in complex with envelope protein GP120, there were substantial structural changes in CCR5 indicating it adopts more of an active-like conformation. On the other hand, CCR5 when it was in complex with MRV always adopted inactive conformation regardless of the protonation state. Hence, CCR5 coreceptor displays conformational heterogeneity not only based on its binding partner but also on the state of the protonation state of a binding site residue GLU2837.39. This outcome is also in accordance with some studies showing that GP120 binding could activate signaling pathways. Additionally, this outcome could also have critical implications for the discovery of novel CCR5 inhibitors to be used as anti-HIV drugs by in silico methods such as molecular docking since consideration of the protonated state of GLU2837.39could be required.