bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of inflammatory biomarkers IL-6, vascular endothelial growth factor and matrix metalloproteinases-9 expression in endometriosis
Authors: Hua Maofang , Wang Yuan , Yao Jun , Zhu Zhenxuan , Liu Xiaoyun , Meng Fanfei , Yu ShuangHua
Published: February 2025

Objective:

Special attention has been paid to genetic mechanisms that might have a significant impact on the context of the risk of developing endometriosis, in recent years. The study aimed to analyze the expression levels of three inflammatory biomarkers Interleukin-6 (IL-6), vascular endothelial growth factor, and matrix metalloproteinases-9, in the increased incidence of endometriosis.

Methods:

The material for genetic testing was tissue slices embedded in paraffin blocks from these patients with endometriosis (I–II) ( n = 24), endometriosis (III–IV) ( n = 24), and the control group ( n = 30) in Lianyungang maternal and child health hospital from January 2020 to December 2023. The expression levels of IL-6, vascular endothelial growth factor, and matrix metalloproteinases-9 genes were determined by the real-time polymerase chain reaction technique.

Results:

The expression levels of IL-6 and vascular endothelial growth factor gene in the peripheral blood and peritoneal fluid of these endometriosis patients were not statistically significant lower than in the control group. Besides, the significant differences were found in IL-6, vascular endothelial growth factor and matrix metalloproteinases-9 between eutopic endometrial tissues of the endometriosis group, compared to the control group; and these increased significantly with the severity of the disease. In addition, there was significant difference in the expression level of matrix metalloproteinases-9 in peripheral blood and peritoneal fluid, and the difference was statistically significant in these patients with stages III–IV, compared with these patients with stages I–II. Among them, the Revised American Society for Reproductive Medicine classification of endometriosis was used in the group of patients with endometriosis.

Conclusion:

These patients with endometriosis showed the significant differences in matrix metalloproteinases-9 expression in peripheral blood, peritoneal fluid, and eutopic and ectopic endometrial tissues as the condition worsens. The research suggested that the determination of matrix metalloproteinases-9 in peripheral blood has certain value in evaluating the condition of endometriosis, which might play an important role in the pathogenesis of endometriosis and be explored for postoperative recurrence monitoring.
Spatialization of Digital Platforms
Authors: Jia Lianrui
Published: February 2025

This article challenges the common tendency to pinpoint a “nationality” to a multi-national capitalist platform company. It calls for a close examination of how platform companies, as capitalist enterprises, organize themselves legally and spatially. The article first reviews how platforms have been studied in relation to space. I then use the case of the Sina model, also known as the Variable Interests Entities (VIE) model, to challenge the meaning of the “Chinese” prefix. This example illustrates that, Chinese or not, capitalist platform companies engineer a composite geography to guarantee maximum flexibility and mobility for the accumulation of private wealth and, in the process, generate great power differentials. In short, this commentary is a call to study digital platforms over the course of capitalism permutations as well as its interpolation and interdependence with existing systems of power.
Framework for Adoption of Enabling Technologies for Improved Outcomes in Spine Surgery
Authors: Muthu Sathish , Ramasubramanian Swaminathan , Jeyaraman Madhan , Hartl Roger , Tavakoli Javad , Cho Samuel K , Scaramuzzo Laura , Singh Hardeep , Louie Philip K , Demetriades Andreas K. , Hsieh Patrick C. , Ćorluka Stipe , Wu Yabin , Chen Xiaolong , Le Hai V. , Vadala Gianluca , Hamouda Waeel , Buser Zorica , Wang Jeffrey C , Meisel Hans-Jorg , Yoon Tim , Jain Amit ,   AO Spine Knowledge Forum Degenerative
Published: February 2025

Study Design

Narrative Review.

Objectives

We aim to investigate the integration and impact of enabling technologies, such as augmented reality, virtual reality, mixed reality, navigation, robotics, and artificial intelligence within the domain of spinal surgery.

Methods

We made a literature review for articles that examined the progression of adoption from initial to subsequent adopters. We also analysed the key determinants that influence adopting these technologies into clinical settings. These include cost-effectiveness, ease of integration, patient acceptance, learning curves, and availability of training resources. Based on the available data a suggestion has been made on the adoption framework for clinical utility.

Results

These technological advancements have the potential to transform surgical practice, offering improved precision and efficiency. The journey toward widespread adoption presents challenges, which include the financial implications, the necessity for specialized training, and the complexities associated with integration. To navigate these hurdles, the study proposes recommendations aimed at improving cost efficiency, streamlining technology integration, investing in professional development, and nurturing a culture of innovation and research.

Conclusions

A framework has been established for the evaluation and integration of state-of-the-art technologies in spinal surgery, thereby maximizing their potential impact on surgical outcomes and patient welfare.
Tear Pattern of the Complete Discoid Lateral Meniscus According to Meniscal Morphology
Authors: Kim Ho Yeon , Kim Jong-Min , Lee Bum-Sik , Ryu Jaejung
Published: February 2025

Background:

The pattern and distribution of tears for the complete discoid lateral meniscus (DLM) are not well documented.

Purpose:

To investigate the prevalence and pattern of tear types for the complete DLM using magnetic resonance imaging (MRI) and arthroscopic data.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

We reviewed consecutive series of 1219 patients (1406 knees) who underwent arthroscopic knee surgery for any pathology and were diagnosed with DLM between January 1998 and December 2022. After excluding cases with incomplete DLM (774 knees) and previous history of ipsilateral knee surgery (55 knees), a total of 486 patients (577 knees; mean age, 37.4 years; range, 5-76 years) with complete DLM were evaluated. Preoperative MRI and intraoperative arthroscopic findings were analyzed to classify tears into the following: peripheral tear—including bucket-handle tear; horizontal tear; radial tear; flap tear; and no tear. In addition, preoperative MRI was used to categorize 2 distinct morphological variants of complete DLM: (1) a block-shaped type with a thick blunt free edge; and (2) a wedge-shaped type with a tapering sharp free edge.

Results:

When categorized by meniscal morphology, 435 knees (75.4%) were classified as block-type and 142 knees (24.6%) as wedge-type complete DLM. Peripheral tears (66.7%) were the most prevalent in the block type, followed by horizontal tears (22.5%) and radial tears (0.7%). In the wedge type, horizontal tears (43%) were observed most frequently, followed by radial tears (18.3%), peripheral tears (11.3%), and flap tears (5.6%).

Conclusion:

A block-shaped morphology was the predominant form of complete DLM in this cohort of operatively treated patients. The wedge-type morphology had a distinctly different tear pattern, with horizontal tears being the most common. While the block type exhibited either a peripheral or horizontal tear, the wedge type was characterized by a greater variation in tear pattern.
Promoting Tourism Sustainability in Jordan: Policy Effectiveness and Stakeholders Perspectives
Authors: Harb Ayman , Alhammad Fawwaz Ali , Almajali Tawfiq Aref , Freewan Ahmed , Shkokani Hanan M. K. , Slehat Muna
Published: February 2025

This study examines the effectiveness of sustainable tourism policies in Jordan, focusing on the roles of key stakeholders, including government bodies, local communities, and tourism businesses. Using a qualitative analysis of focus group discussions, it analyzes the challenges and opportunities in implementing sustainable tourism policies and strategies. While frameworks such as the National Tourism Strategy and Green Growth Action Plan (2021–2025) provide a foundation, concerns persist regarding exploiting natural resources and limited stakeholders’ engagement. The findings stress the need for enhanced policy coordination, greater community involvement, and robust climate change mitigation measures. The study offers actionable recommendations to strengthen the sustainability of Jordan’s tourism sector, ensuring long-term environmental, economic, and cultural benefits.
A Guide to Causal Inference in Life-Event Studies
Authors: Lawes Mario , West Stephen G. , Eid Michael
Published: February 2025

There is considerable interest in studying the impact of major life events (e.g., marriage, job loss) on people’s lives. This line of research is inherently causal: Its goal is to study whether life events cause changes in the examined outcomes. However, because major life events cannot be randomly assigned, studies in this area necessarily rely on longitudinal observational data. In this article, we provide guidelines for researchers interested in studying life events in an explicitly causal framework. Although focused on life-event studies for substantive context, many recommendations also apply to longitudinal observational studies more broadly. We begin by emphasizing the importance of clearly specifying the causal estimand and describe conditions in which the defined causal estimand can be identified. Then, we discuss the features and challenges of the two main analytical approaches to causal inference in life-event studies: difference-in-difference designs with a (matched) comparison group that attempt to separate event-related changes from normative changes and within-person designs that control for all time-invariant person-level confounders. We describe how the desired causal effect can be estimated in these designs and provide recommendations for when to apply each modeling strategy. In addition, we present methods for conducting sensitivity analysis, probing the robustness of the estimated causal effects, and evaluating the generalizability of the results. We conclude by describing how new specialized panel studies can be designed to examine the impact of various life events in more controlled settings.
Acute Coronary Syndrome Following Consumption of Kiwi Juice: A Rare Presentation
Authors: Vijayachandra Yerramareddy , Wilson Antony , Sreeram Jayalakshmi , Kumar Aishwarya Mahesh
Published: February 2025

Kounis syndrome is a rare phenomenon wherein cardiovascular symptoms develop after allergic or hypersensitivity reactions. We present the case of a 51-year-old male who developed anaphylactic shock after consuming kiwi fruit juice, followed by acute ST-elevation myocardial infarction (STEMI). Coronary angiography showed normal coronary arteries. This case emphasizes the importance of considering Kounis syndrome in patients with anaphylaxis and acute coronary symptoms.
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

Background

Idiopathic 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.

Methods

Explant 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.

Results

Human 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.

Conclusions

Plasma 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

Background

We 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.

Methods

Children 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.

Results

The 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).

Conclusion

In 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

Background

Because 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.

Methods

This 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.

Results

Among 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.

Conclusion

Lymphocyte 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

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

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

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

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

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

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

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

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.
Haemoproteus tartakovskyi and Plasmodium relictum (Haemosporida, Apicomplexa) differentially express distinct 18S rRNA gene variants in bird hosts and dipteran vectors
Authors: Harl Josef , Himmel Tanja , Ilgūnas Mikas , Chagas Carolina Romeiro Fernandes , Matt Julia , Nedorost Nora , Iezhova Tatjana A. , Valkiūnas Gediminas , Weissenböck Herbert
Published: February 2025

Background

Most mammalian Plasmodium species possess distinct 18S ribosomal RNA (rRNA) gene copies, which are differentially expressed in vertebrate hosts and mosquito vectors. Although similar sequence patterns were found in avian haemosporidian parasites, expression patterns have not been studied yet. This study aimed to test whether 18S variants of Plasmodium relictum SGS1 and Haemoproteus tartakovskyi SISKIN1 are expressed differentially in bird hosts and dipteran vectors using real-time quantitative polymerase chain reaction (qPCR) and chromogenic in situ hybridization (CISH).

Methods

Eurasian siskins (Spinus spinus) experimentally infected with P. relictum SGS1 and naturally infected with H. tartakovskyi SISKIN1 were used. Culex quinquefasciatus mosquitoes (SGS1) and Culicoides nubeculosus biting midges (SISKIN1) were fed on the blood of infected birds and maintained for several days to allow for the development of oocysts and sporozoites. Total RNA was extracted from bird blood and a subset of the dipteran vectors during each stage of parasite development, followed by qPCRs specifically targeting distinct 18S variants of the two parasites. Organs of the donor birds and whole bodies of the vectors were examined histologically using CISH by targeting different 18S variants of the parasites.

Results

Plasmodium relictum SGS1 expressed two 18S variants in bird blood and mosquitoes, but their expression levels were reversed in birds and vectors, with one variant being preferentially expressed over the other. Using CISH, oocysts were stained with probes targeting both 18S variants, but sporozoites could not be detected, suggesting a suboptimal development of the parasites. Haemoproteus tartakovskyi SISKIN1, which features three distinct 18S variants, expressed one 18S variant in bird blood and two variants in the biting midges, while no signals were detected for the third variant. The results were corroborated by CISH, but surprisingly, some oocysts were also stained by the probe targeting the third variant.

Conclusions

The results indicate that distinct 18S variants of the two parasite species are differentially expressed in bird hosts and vectors. Moreover, for the first time, we provide visualizations of avian haemosporidian oocysts in tissue sections of the vectors, with the discovery of extraintestinal development of oocysts in SISKIN1-infected biting midges.

Graphical Abstract
The causal relationships between gut microbiota and venous thromboembolism: a Mendelian randomization study
Authors: Huang Pin , Xiao Ying , He Ye
Published: February 2025

Background

Venous thromboembolism (VTE) is still one of the most severe health issues, increasing mortality and lengthening hospital stays. Different abundances of gut microbiota have been clinically linked to VTE and coagulopathy. However, whether gut microbiota affected VTE formation remained uncertain.

Methods

The causative links between VTE and 211 gut microbiota at phylum, class, order, family and genus level were separately investigated using two-sample Mendelian Randomization (MR) analysis. Firstly, single nucleotide polymorphisms (SNPs) locus-wide significantly (P < 1.0 × 10− 5) related with gut microbiome abundance were extracted from large genome-wide analysis (GWAS) meta-analysis summary data. Instrumental variables (IVs) without pleiotropy were selected using the PhenoScanner and MR PRESSO test. Then, the MR analysis was implemented using the inverse variance weighted (IVW) method. Moreover, weighted median method, MR Egger method, simple median method and MR PRESSO were conducted to validate the causal associations. The reliability of the results was also assessed utilizing various sensitivity analyses, reverse MR analysis and multivariate Mendelian Randomization analysis (MVMR).

Results

We found the phylum Firmicutes was robustly protective against VTE with MR analysis. Moreover, five taxa of Actinobacteria phylum (Bifidobacteriales order, Actinomycetales order, Bifidobacteriaceae family, Actinomycetaceae family, Slackia genus) and two taxa of Firmicutes phylum (Bacillales order, Lachnospiraceae UCG-010 genus) were suggestively protective for VTE. While three taxa of Firmicutes phylum (Bacilli class, Lactobacillales order and Lactococcus genus) might suggestively increase the risk of VTE. Sensitivity analyses indicated no significant horizontal pleiotropy, heterogeneity, or reverse causal associations. Furthermore, MVMR analysis unveiled independently positive causal association of Firmicutes phylum and Lachnospiraceae UCG-010 genus with risk of VTE.

Conclusion

Two taxa of gut microbes (Firmicutes phylum and Lachnospiraceae UCG-010 genus) were independently protective against VTE, which suggests a potential avenue for developing new cost-effective strategies with minor side effects for VTE prevention and treatment.
A social return on investment analysis of patient-reported outcome measures in value-based healthcare
Authors: Crane Ellie , Noyes Jane , Bianchim Mayara S. , Mclaughlin Leah , Cahill Adele , Roberts Gareth , Stringer Carys
Published: February 2025

Objectives

There is growing interest in the use of Patient Reported Outcome Measures (PROMs) to improve patient and healthcare service outcomes. This study aimed to measure the social and economic value of PROMs implemented within a VBHC framework.

Methods

We conducted a Social-Return on Investment (SROI) analysis in Epilepsy, Heart Failure, and Parkinson’s Disease services, to measure the value generated by PROMs for patients and the healthcare provider.

Results

The SROI analysis revealed substantial variation in the value derived from the PROMs intervention across different services. The highest value was observed in Heart Failure with an SROI ratio of 5.55:1, which represents a substantial return on investment for patients and services. In contrast, the Parkinson’s Disease service had small return on investment from PROMs with an SROI ratio of 1.29:1. In Epilepsy, the social value derived from PROMs was proportionally less than the investment made, with an SROI ratio of 0.85:1.

Conclusion

These findings demonstrate the complexities of implementing PROMs within a clinical context, and careful consideration is likely needed in selecting suitable services and tailoring the implementation of PROMs to effectively meet specific service and patient requirements. Where PROMs yielded low or no value, the lack of return-on-investment prompts a strategic re-evaluation regarding how PROMs are funded, implemented, and utilized. As the first economic evaluation of PROMs in clinical practice, this study is a novel contribution to the emergent VBHC and PROMs evidence base. Furthermore, the findings from this study will inform recommendations to improve PROMs delivery across Wales.
Exploring risk resistant banking strategies: implications for sustainable practices
Authors: Ashik-Uz-Zaman  , Abedin Md.Thasinul , Hossain Md.Sharif
Published: February 2025

The subprime mortgage crisis has sharply traumatized the world financial system and subsequently put a question on the resilience. Even the commercial banks from a strong economy like the USA have experienced abrupt collapse. Such a scenario has induced deep concern among the stakeholders of the banking sector globally. Almost all the recent bank failure cases are centered on incapacitated risk governance mechanisms. Credit risk, liquidity risk and capital risks are the fundamental contributors of a risk management framework as per the recent empirical evidence and they are very much intertwined. We have explored the expert justification of the magnitude of these pivotal risks through an open-ended interview approach in order to formulate a sophisticated risk governance framework. We have also explored the determinants of these key risks using both the difference GMM and the System GMM approach on panel data from 2005 to 2020 of listed Bangladeshi banks. We have found that capital adequacy is significantly affected by asset turnover and cash in a positive manner, whereas management efficiency and non-performing loan (NPL) ratio negatively affect it. Asset turnover, experience and cost-to-income ratio negatively affect the credit risk, whereas NPL ratio and liquidity risk ratio influence it in a significant positive manner. Liquidity risk is significantly affected mostly by asset turnover, return on assets, cost-to-income ratio and credit risk. Following the empirical assessment, we have suggested a few policies for the regulatory authority with a view to making the banking practice more risk-resilient and sustainable.
“I Would Advise That It Be Kept from the Schools at All Cost”: The Influenza of 1918–1920 at Nonreservation Indian Boarding Schools
Authors: Adams Mikaëla M. , Dimka Jessica , Mamelund Svenn-Erik , Sattenspiel Lisa
Published: February 2025

In this article, the authors investigate the 1918–20 influenza pandemic in the federal government’s nonreservation Indian boarding schools. Nonreservation boarding schools, which served approximately 6,200 Indigenous youths in 1919, provide a particularly fruitful terrain for analysis due to the detailed records, reports, and correspondence they shared with the Indian Office before, during, and after the pandemic. This rich source base offers a rare opportunity to analyze comparatively how these institutions handled the influenza crisis and how different factors resulted in different outcomes. The authors first describe the Indigenous education system at the time, then document and evaluate patterns of infection, mitigation efforts and medical aid, and responses by the superintendents and Indian Office to the overall experience. Drawing from this discussion, they also use quantitative analysis to investigate the roles of different factors in morbidity and mortality outcomes.
Psychedelic Codes and Close Listening to South Korean Fiction, 1971 – 1989
Authors: Waddell Ethan
Published: February 2025

This article draws upon the vernacularized psychedelic rock of Shin Joong Hyun (Sin Chung-hyŏn, b. 1938) and youth culture fiction of Ch’oe In-ho (1945–2013) in order to formulate a method for close listening to literary articulations of a shared artistic pursuit of individual liberation through the undermining of established modes of feeling and consciousness. The article overviews psychedelic aesthetics and coding and explicates their recodification by novelist Yi In-sŏng (b. 1953). It then contextualizes the coeval advent of psychedelic counterculture and youth culture in South Korea vis-à-vis the emergence of a nascent middle class. Next the article illustrates how Ch’oe transposed cosmopolitan musical sensibilities onto stories of alienated urban youth and daydreams of class mobility. It then moves from textual reference to formal homology, interpreting the global countercultural call for self-liberation in two novellas by Ch’oe through psychedelic musical codes of noise and upward movement, respectively. Finally, the conclusion draws upon the work of Kim Ch’ae-wŏn (b. 1946) to reflect upon the legacy of vernacularized psychedelic codes in Korean literature. The article argues that close listening to heterodox and hallucinatory resonances across popular music and understudied works of fiction by well-known authors complicates conventional understandings and cultural histories of subversive art.
Sound, Gender, and the Thing: Earphone and Miss Earphone in Shanghai Cinema, 1939–1949
Authors: Cao Qilin
Published: February 2025

This article argues that the earphone is a microcosm of the broader material and societal changes that occurred within the film translation industry in Republican Shanghai. As one of the acoustic devices that shaped the transmission and consumption of sounds in the modern world, the earphone was introduced to Shanghai cinema in 1939 to interpret Western sound films for Chinese audiences. The application of earphones gave rise to a new profession, “Miss Earphone,” whose practitioners were exclusively female, thereby precipitating a counteraction to the male-dominated print translation industry. Such an abrupt transformation brings to the fore the role of the earphone in mediating the entanglement of media, gender, and language. Through the prism of thing theory, this article recognizes the earphone as not only a technical object that assisted the translation enterprise but also a thing through which a rehistoriography could be undertaken concerning media development, the gendering of the labor force, and the remolding of mass entertainment. Correspondingly, within the purview of this essay is not only the human-machine interplay but also the illocutionary force of the earphone in articulating the (re)formation of the human-object relationship within a larger circuit of material development. The thingness of the earphone is, as this article argues, intrinsically inherent in the cross-linguistic endeavors of Shanghai cinema and invariably conditioned by the dynamic interactions between the nonhuman—mediums and techniques—and the human—genders, bodies, senses, and affects.