bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct mural cells and fibroblasts promote pathogenic plasma cell accumulation in idiopathic pulmonary fibrosis
Authors: Yang Zhi , Cao Gaoyuan , Tan Xiaosheng , Orfanos Sarah , Jude Joseph , Barbet Gaetan , An Steven S. , Jiang Dianhua , Panettieri Reynold A. , Yang Qi 
Published: February 2025

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterized by significant, but poorly understood immune and antibody responses. This study examines the spatial transcriptomes and microenvironmental niches of antibody-producing plasma cells and tertiary lymphoid structures (TLS) in IPF lungs, and the molecular pathways influencing antibody accumulation and pulmonary fibrosis.MethodsExplant lung tissues from IPF patients and control normal lungs were used for spatial transcriptome assays and validating RNA-scope and immunofluorescence assays. Fibroblasts derived from IPF and control lungs were examined for their capability to attract plasma cells. Neutralizing antibodies were administered to investigate molecules affecting pulmonary plasma cell accumulation and fibrosis in bleomycin-treated mice.ResultsHuman IPF lungs exhibited a remarkably widespread distribution of plasma cells and local antibodies in the fibrotic regions, disseminating from plasma cell-generating TLS. Novel mural cells wrapped the vessels in TLS regions, expressing CCR7 ligands that attracted T cells into TLS to promote plasma cell generation. Distinct IPF-associated fibroblasts further secreted CXCL12, providing an extramedullary niche to foster the dissemination and accumulation of plasma cells in the fibrotic regions. Neutralization of CCR7 ligands or CXCL12 reduced plasma cell and local antibody accumulation in the lungs of bleomycin-treated mice, leading to reduced TGFβ concentrations and alleviated pulmonary fibrosis.ConclusionsPlasma cells and local antibodies are widely distributed in the fibrotic regions of IPF lungs. Distinct subsets of IPF-associated mural cells and fibroblasts promote pathological plasma cell and antibody accumulation. These findings have potential implications for strategies aimed at targeting immune and antibody responses to combat IPF.
Pulmonary functıon ın chıldren post-empyema: spırometryversusLung Clearance Index
Authors: Senturk Mehmet Cihan , Gokdemir Yasemin , Ergenekon Almala Pinar , Altas Zeynep Meva , Eralp Ela Erdem , Yegit Cansu Yilmaz , Cenk Muruvvet , Kalyoncu Mine , Kiyan Gursu , Kanmis Saniye Girit , Atag Emine , Gulec Seda Geylani , Karakoc Fazilet , Karadag Bulent 
Published: February 2025

BackgroundWe hypothesize that Lung Clearance Index (LCI) would be superior to spirometry in diagnosing early-stage respiratory diseases earlier and, more precisely, in patients who received medical or surgical treatment for empyema.MethodsChildren over five diagnosed with empyema at least six months ago were recruited. In addition, a control group was created from healthy individuals between the ages of 5 to 18 years. Spirometry and LCI were performed in both groups.ResultsThe spirometric values of the patients were compared with the spirometric values of the controls; there was no significant difference between the patient and control groups FEV1, FVC, and FEV1/FVC z scores results when compared. (p: 0.610, p: 0.342, p: 0.298; respectively). In addition, when the LCI 2.5% values of the patients were compared with the LCI 2.5% values of the controls and reference values, the LCI 2.5% was found to be significantly abnormal (p: 0.003 and p:0.005, respectively).ConclusionIn the long-term follow-up of patients who received inpatient treatment for empyema, airway disease that could not be detected by spirometry was obtained using the LCI method.
Evaluation of a screening protocol for telomere biology disorders in individuals with interstitial lung disease undergoing lung transplant evaluation
Authors: Zhu Daisy , Patel Namrata B. , Pishko Allyson M. , Weinberg Ethan M. , Takako Tanaka I. , Kallish Staci , Johnson F. Bradley , Babushok Daria V. , Courtwright Andrew M. 
Published: February 2025

BackgroundBecause of the potential for extrapulmonary disease, it is important for lung transplant programs to identify telomere biology disorder-related interstitial lung disease (TBD ILD). The aim of this study was to evaluate a TBD phenotype screen among ILD patients undergoing lung transplant evaluation, including the sensitivity and specificity of individual phenotype screening questions and the characteristics of patients with TBD identified outside of the screening protocol.MethodsThis was a retrospective cohort study of adults with ILD who underwent lung transplant evaluation from 1/1/2018–2/28/2023. The TBD phenotype screen included early graying, family history of ILD, and unexplained liver disease, cytopenias, or macrocytosis. TBD screen positive patients underwent telomere length (TL) testing.ResultsAmong 383 patients evaluated, 92 (24.0%) had a positive phenotype screen. Fifty-eight (63.0%) had early graying, 39 (42.4%) had a first-degree relative with ILD, and 29 (31.5%) had unexplained macrocytosis or cytopenias. Using granulocyte and lymphocyte TL <10th percentile, 51 (55.4%) patients met criteria for a TBD. Early graying had the highest sensitivity for TBD (72.5%) with specificity increasing with the number of positive screening questions. Among the 23 patients who underwent TL testing outside of the screening protocol—most commonly because of an early age of onset of ILD—8 (34.8%) had TL between 1st–10th percentile.ConclusionLymphocyte and granulocyte TL <10th is common among TBD phenotype screen positive ILD patients undergoing transplant evaluation. Inclusion of additional screening questions related to age of onset of ILD could improve the sensitivity of the protocol for short TL.
Cancer-secreted exosomal miR-1246 promotes colorectal cancer liver metastasis by activating hepatic stellate cells
Authors: Liu Xiaolong , Liu Jialong , Wang Xuanyin , Zou Yang , Tao Xinyi , Li Jingyu , Ye Mengnan , Xu Wanbei , Deng Yunyao , Liu Lixin , Sun Jingbo , Zhang Qingling 
Published: February 2025

Abstract
Colorectal cancer liver metastases (CRLM) are the primary cause of mortality in colorectal cancer (CRC) patients, highlighting the importance of understanding the underlying mechanisms. The tumor microenvironment (TME) and its interaction with tumor cells play a crucial role in CRLM progression. Notably, the stability and peak levels of tumor-derived exosomal miRNAs facilitate intercellular communication in the TME. Hepatic stellate cells (HSCs), key liver mesenchymal cells, constitute about 33% of the liver's nonsolid cell population and exhibit plasticity. However, the specific role of tumor-derived exosomal miRNAs in the crosstalk between HSCs and tumor cells during the CRLM process remains unclear. We studied CRC-secreted exosomal miR-1246 and its impact on HSCs, as well as its effects on CRC cell proliferation and metastasis. Our findings demonstrate that CRC-secreted exosomal miR-1246 can be internalized by HSCs, leading to their activation and facilitating the metastatic potential of CRC cells. Mechanistically, exosomal miR-1246 targets INSIG1, resulting in SREBP2 nucleation and cholesterol metabolism alterations. This accumulation of free cholesterol (FC) regulates the TLR4/NF-κB/TGF-β pathway, promoting HSC activation. Activated HSCs, in turn, enhance liver metastasis of CRC cells through the TNFSF13/TNFRSF13B axis. Our study reveals the role of CRC-secreted exosomal miR-1246 in triggering HSC activation and reprogramming the TME, ultimately facilitating liver metastasis in CRC patients. Exosomal miR-1246 could serve as a potential non-invasive biomarker for predicting colorectal cancer liver metastasis, enhancing our understanding of CRC-associated liver metastases.

Graphical abstract
Matrix metalloproteinases and their tissue inhibitors as upcoming biomarker signatures of connective tissue diseases-related interstitial lung disease: towards an earlier and accurate diagnosis
Authors: Pulito-Cueto Verónica , Atienza-Mateo Belén , Batista-Liz Joao C. , Sebastián Mora-Gil María , Mora-Cuesta Víctor M. , Iturbe-Fernández David , Izquierdo Cuervo Sheila , Aguirre Portilla Carolina , Blanco Ricardo , López-Mejías Raquel 
Published: February 2025

Abstract

Background
Lack of understanding of interstitial lung disease (ILD) associated with systemic sclerosis (SSc) and rheumatoid arthritis (RA) hinders the early and accurate identification of these devastating diseases. Current clinical tools limitations highlight the need to complement them with accessible and non-invasive methods. Accordingly, we focused on identifying useful matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) as new biomarkers with clinical value in the diagnosis and prognosis of RA-ILD+ and SSc-ILD+.

Methods
Peripheral blood was collected from patients with RA-ILD+ (n = 49) and SSc-ILD+ (n = 38); as well as with RA-ILD- (n = 25), SSc-ILD- (n = 20) and idiopathic pulmonary fibrosis (IPF) (n = 39). MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, TIMP-1, and TIMP-2 serum levels were measured using xMAP Technology.

Results
Concerning early connective tissue disease (CTD)-ILD+ diagnosis, increased MMP-7, MMP-9, MMP-10, and MMP-12 levels were found in RA-ILD+ and SSc-ILD+ patients in relation to RA-ILD- and SSc-ILD- patients, respectively. RA-ILD+ patients showed higher MMP-2 levels and lower TIMP-1 levels than RA-ILD- patients. Interestingly, a reliable utility for identifying ILD in CTD was confirmed for the MMP-2, MMP-7, MMP-9, MMP-10, MMP-12, and TIMP-1 combination in RA and MMP-7, MMP-9, MMP-10, and MMP-12 combinatorial signature in SSc. Regarding accurate CTD-ILD+ diagnosis, RA-ILD+ and SSc-ILD+ patients showed lower MMP-7 and MMP-10 levels than IPF patients. Lower MMP-9 and TIMP-1 levels and higher MMP-3 levels were found in RA-ILD+ compared to IPF. Remarkably, effectively better differentiation between CTD-ILD+ and IPF was confirmed for a 5-biomarker signature consisting of MMP-3, MMP-7, MMP-9, MMP-10, and TIMP-1 in RA as well as for the MMP-7 and MMP-10 combination in SSc. Finally, in RA-ILD+ patients, higher MMP-10 levels were associated with worse pulmonary function, increased MMP-2 levels were related to the treatment with conventional synthetic disease-modifying anti-rheumatic drugs, and decreased TIMP-1 levels were linked with positivity rheumatoid factor status.

Conclusions
MMPs and TIMPs form combinatorial biomarker signatures with clinical value for non-invasive, early, and accurate diagnosis of RA-ILD+ and SSc-ILD+, constituting promising screening tools in clinical practice.
Recurrent strokes as the sole manifestation of antineutrophil cytoplasmic antibody associated vasculitis in a patientwith panuveitis: a case report
Authors: Seraj Hadeel , Alshalan Hanan A. , Alemam Reham , Omair Mohammed A. 
Published: February 2025

Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of rare, autoimmune conditions characterized by widespread, multisystemic inflammation of small to medium-sized blood vessels. We present a case report of a 46-year-old male with a history of prior ischemic strokes and recurrent bilateral non-granulomatous panuveitis associated with a strongly positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) titer. Initial treatment with steroids, methotrexate, and rituximab were ineffective, but the condition responded moderately to cyclophosphamide. This case underscores the importance of considering AAV in patients with unexplained ocular inflammation and highlights the role of c-ANCA testing in diagnosing and managing such cases, even in the absence of classic systemic symptoms.
Impact of SMOFlipid emulsion integration in total parenteral nutrition on inpatient outcomes and economic burden for preterm neonates: a retrospective cohort study
Authors: Refaay Mohamed Emad Eldin , Yassine Omaima Gaber , Abu-Sheasha Ghada Ahmed , Zaki Adel 
Published: February 2025

Abstract

Introduction
The use of lipid emulsion in TPN for preterm infants can affect clinical outcomes.

Objective
To assess the potential beneficial health outcomes and economic impact of including SMOFlipid emulsion in TPN for preterm infants, specifically focusing on the incidence of neonatal sepsis, LOS in the NICU, and the associated economic implications from the perspective of healthcare providers in Egypt.

Methods
A record-based retrospective cohort study was conducted in 2021. We collected data from the neonatal intensive care unit (NICU) of Alexandria University Pediatric Hospital, Egypt, for newborns who received TPN. The collected data included gestational age, birth weight, sex, diagnosis of sepsis, LOS in the NICU and type of TPN. Our sample consisted of 103 newborns who received TPN with SMOFlipid and 104 newborns who received TPN without SMOFlipid. Using the propensity score, the study groups’ baseline characteristics were balanced. Odds ratios were estimated using logistic regression, and the statistical significance was set at < 0.05.

Results
Compared to TPN without lipids, the use of SMOFlipid was associated with an observed reduction in the risk of sepsis (OR = 0.64, 95% CI: 0.272–1.51), as well as a difference in the mean reduction in hospital stay (4.12 days, p = 0.08). Furthermore, using SMOFlipid was associated with a significant mean reduction in cost of 6,396 EGP (95% CI: 1,491–11,546 EGP).

Conclusion
The integration of SMOFlipid into TPN for preterm infants is associated with decreased incidence of sepsis, reduced NICU stay, and significant cost savings, warranting consideration for standard care practices.
Mitophagy is required to protect against excessive skeletal muscle atrophy following hindlimb immobilization
Authors: Rahman Fasih A. , Graham Mackenzie Q. , Adam Amanda M. , Juracic Emma S. , Tupling A. Russell , Quadrilatero Joe 
Published: February 2025

Abstract

Background
Skeletal muscle atrophy involves significant remodeling of fibers and is characterized by deficits in mitochondrial content and function. These changes are intimately connected to shifts in mitochondrial turnover, encompassing processes such as mitophagy and mitochondrial biogenesis. However, the role of these mitochondrial turnover processes in muscle atrophy remains poorly understood.

Methods
We used a novel mitophagy reporter model, mt-Keima mice, to perform hindlimb immobilization and accurately measure mitophagy. A comprehensive set of analyses were conducted to investigate biochemical and molecular changes at the muscle and mitochondrial levels. We also performed image analyses to determine mitophagic flux. To further explore the role of mitophagy in immobilization-induced atrophy, we treated animals with N-acetylcysteine (NAC; 150 mg/kg/day) to modify reactive oxygen species (ROS) signaling and colchicine (0.4 mg/kg/day) to inhibit autophagy.

Results
Our study revealed that hindlimb immobilization leads to muscle weakness and atrophy of fast-twitch muscle fibers (types IIA, IIX, and IIB), with recovery observed in IIA fibers following remobilization. This atrophy was accompanied by a significant increase in mitophagic flux. Additionally, immobilization induced notable mitochondrial dysfunction, as shown by diminished respiration, increased mitochondrial ROS, and greater whole muscle lipid peroxidation. Treatment of immobilized mice with NAC enhanced mitochondrial respiration and reduced ROS generation but suppressed mitophagic flux and intensified atrophy of type IIX and IIB fibers. Additionally, administration of colchicine to immobilized mice suppressed mitophagic flux, which also exacerbated atrophy of IIX and IIB fibers. Colchicine treatment led to significant reductions in mitochondrial function, accompanied by CASP9 and CASP3 activation.

Conclusion
These findings emphasize the role of mitophagy in limiting excessive muscle atrophy during immobilization. Targeting mitophagy may offer new strategies to preserve muscle function during prolonged periods of immobilization.
New horizons for the therapeutic application of nanozymes in cancer treatment
Authors: Malla Pravanjan , Wang Yu-Ming , Su Chia-Hao 
Published: February 2025

Abstract
The advent of nanozymes has revolutionized approaches to cancer diagnosis and therapy, introducing innovative strategies that address the limitations of conventional treatments. Nanozyme nanostructures with enzyme-mimicking catalytic abilities exhibit exceptional stability, biocompatibility, and customizable functions, positioning them as promising tools for cancer theranostics. By emulating natural enzyme reactions, nanozymes can selectively target and eradicate cancer cells, minimizing harm to adjacent healthy tissues. Nanozymes can also be functionalized with specific targeting ligands, allowing for the precise delivery and regulated release of therapeutic agents, improving treatment effectiveness and reducing adverse effects. However, issues such as biocompatibility, selectivity, and regulatory compliance remain critical challenges for the clinical application of nanozymes. This review provides an overview of nanozymes, highlighting their unique properties, various classifications, catalytic activities, and diverse applications in cancer treatments. The strategic oncological deployment of nanozymes could profoundly impact future advancements in personalized medicine, highlighting recent progress and prospective directions in enzyme-mimetic approaches for cancer treatment. This review summarizes an overview of nanozymes, highlighting their unique properties, various classifications, catalytic activities, and diverse applications in cancer treatments.

Graphical Abstract
A political economy analysis of the legislative response to unhealthy food and beverage marketing in Chile, Canada and the UK
Authors: Sing Fiona , Mackay Sally , Swinburn Boyd , Garton Kelly 
Published: February 2025

Abstract
United Nations bodies call for legal responses to restrict children’s exposure to unhealthy food marketing; however, few governments have introduced legislative controls. This research studies the underlying political economy influences that impacted the introduction of legal responses. We used a multiple case study methodology to examine the political economy influences on the policy process in three contexts (Chile, Canada and the UK). Data from documentary evidence and 21 semi-structured key informant interviews were analysed using a political economy framework studying the institutions, interests, ideas and the associated power dynamics that shaped the policy process. The prevailing neoliberal ideologies and overarching institutional paradigm, in which all actors were operating, meant any form of government intervention had to be justified, evidence-based and no more intrusive on commercial enterprise and public life than necessary. The neoliberal paradigm permeated each of the political economy elements (institutions, ideas and interests). In addition, its influence was observed in all stages of the policy process, from introduction through to adoption of the resulting law or regulation, and experienced in both the executive and legislative branches of government. A paradigm shift away from the protection and primacy of commercial enterprise and limited government interference would reduce the barriers governments face when introducing legislative responses to unhealthy food marketing. These dynamics may be tempered if institutional, actor and discursive power is harnessed in support of the legitimate public health measure, which would involve a strong mandate for the ministry responsible and a dedicated and influential policy entrepreneur.
- Provides an insight into how three different governments legislated unhealthy food marketing.
- Provides lessons for other governments about what challenges those countries faced and how they overcame them.
- Considers the political reality behind policy making that impacts on how evidence-based policy making occurs.
A multi-level implementation strategy to increase adoption of chiropractic care for low back pain in primary care clinics: a randomized stepped-wedge pilot study protocol
Authors: Roseen Eric J. , Bussières André , Reichman Rocky , Bora Celia , Trieu Jennifer , Austad Kirsten , Williams Charles , Fischer Ryan A. , Parrilla Danielle , Laird Lance D. , LaValley Michael , Evans Roni L. , Saper Robert B. , Morone Natalia E. 
Published: February 2025

Abstract

Introduction
Limited adoption of first line treatments for low back pain (LBP) in primary care settings may contribute to an overreliance on pain medications by primary care providers (PCPs). While chiropractic care typically includes recommended nonpharmacologic approaches (e.g., manual therapy, exercise instruction, advice on self-care), implementation strategies to increase adoption of chiropractic care for LBP in primary care clinics are understudied, particularly in underserved communities.

Methods
We will use a stepped-wedge cluster randomized controlled pilot trial design to evaluate the feasibility of a multi-level implementation strategy to increase adoption of chiropractic care for LBP in primary care clinics at community health centers. Key barriers and facilitators identified by site champions and other key stakeholders will help us to develop and tailor implementation strategies including educational materials and meetings, developing a network of local chiropractors, and modifying the electronic health record to facilitate referrals. Three primary care clinics will be randomized to receive the implementation strategy first, second, or third over a fourteen-month study period. At our first clinic, we will have a four-month pre-implementation period, a two-month implementation deployment period, and a subsequent eight-month follow-up period. We will stagger the start of our implementation strategy, beginning in a new clinic every two months. We will evaluate the proportion of patients with LBP who receive a referral to chiropractic care in the first 21 days after their index visit with PCP. We will also evaluate adoption of other guideline concordant care (e.g., other nonpharmacologic treatments) and non-guideline concordant care (e.g., opioids, imaging) over the study period.

Discussion
LBP is currently the leading cause of disability worldwide. While there are several treatment options available for individuals with LBP, patients in underserved populations do not often access recommended nonpharmacologic treatment options such as chiropractic care. The results from this study will inform the development of practical implementation strategies that may improve access to chiropractic care for LBP in the primary care context. Furthermore, results may also inform policy changes needed to expand access to chiropractic care in underserved communities.

Clintrials.gov NCT#
NCT06104605.