bluuebunny/crossref_metadata_2025 huggingface dataset:
The Contribution of Inclusive Theology to Religious Pluralism Among Indonesian Christians
Authors: Pranoto Fatony
Published: February 2025

This study explores the contribution of inclusive theology in enhancing the understanding of religious pluralism among Indonesian Christians. The background of this research is the complexity of religious diversity in Indonesia and the importance of fostering interfaith harmony. This study aims to: (1) understand the experiences and perceptions of Christians regarding religious pluralism, (2) analyze the contribution of inclusive theology in enhancing the understanding of religious pluralism among Indonesian Christians, and (3) formulate the practical implications of inclusive theology in strengthening religious pluralism within the Christian community in Indonesia. Using a literature study method with a qualitative approach, this research examines the role of inclusive theology in fostering comprehension and acceptance of religious pluralism. The findings indicate that inclusive theology plays a crucial role in constructing a more open theological framework, cultivating values of tolerance, and strengthening the church’s role in fostering interfaith relationships. The practical implications of this study include the integration of inclusive theological education, interfaith dialogue, and social justice advocacy. By understanding and applying the principles of inclusive theology, Christian communities can contribute to building a more harmonious and tolerant society.
Analytical and clinical validation of a novel MeltPlus TB-NTM/RIF platform for simultaneous detection of Mycobacterium tuberculosis complex, Non-Tuberculous Mycobacteria and rifampicin resistance
Authors: Wang Zhuo , Zou Yuanwu , Wei Zihan , Bai Guanghong , Wang Xiaolin , Qu Shaoyi , Shi Jie , Jiang Yaping , Gu Cuijiao
Published: February 2025

Background

Rapid and accurate diagnosis of tuberculosis, particularly rifampin (RIF)-resistant tuberculosis (RR-TB) and Non-Tuberculous Mycobacteria (NTM), is essential for implementing appropriate proper therapy to benefit patients and improve TB/NTM patient management.

Methods

In this study, we developed a novel MeltPlus MTB-NTM/RIF platform, designed to simultaneously detect Mycobacterium tuberculosis complex (MTBC), NTM and RIF resistance. The platform was evaluated for its limit of detection (LOD) and specificity before clinical validation, followed by a prospective single-center study in patients with presumptive TB cases.

Results

The calculated LOD for MTBC, NTM and RIF susceptibility was found to be 10.31 CFU/mL, 57.55 CFU/mL and 48.584 CFU/mL, respectively. The assay showed a sensitivity of 98.76% (95% CI: 96.41-99.74%) and a specificity of 94.42% (95% CI: 90.82-96.92%) for MTBC detection compared to the bacteriological TB standard. For NTM detection, the assay demonstrated a sensitivity of 91.98% (95% CI: 76.32-98.14%) and a specificity of 99.59% (95% CI: 98.54-99.95%). RIF resistance detection showed a sensitivity of 90.24% (95% CI:76.87-97.28%) and specificity of 95.98% (95% CI: 91.89-98.37%), with a high level of diagnostic agreement (Kappa: 0.8338) compared to GeneXpert. Sanger sequencing revealed that novel assay correctly classifies 98.6% of study cases as RIF resistant or susceptible, slightly higher that of GeneXpert.

Discussion

These findings indicate that the novel MeltPlus MTB-NTM/RIF platform provides a rapid and accurate method for the simultaneously detecting MTBC, NTM, and RIF resistance, making it a promising tool for clinical TB/NTM diagnosis and management, further multi-center and field studies are recommended to validate its broader applicability.
Type 2 diabetes mellitus’ impact on heart failure patients’ exercise tolerance: a focus on maximal fat oxidation during exercise
Authors: Zhu Huiying , Pan Jianchao , Wen Jianxuan , Dang Xiaojing , Chen Xiankun , Fan Yunxiang , Lu Weihui , Jiang Wei
Published: February 2025

Objective

To explore the impact of type 2 diabetes mellitus (T2DM) on exercise tolerance and fat oxidation capacity in patients with heart failure (HF).

Methods

We retrospectively analyzed 108 Chinese patients with HF who were divided into a diabetic group (T2DM group, n = 47) and a non-diabetic group (non-T2DM group, n = 61). All subjects completed cardiopulmonary exercise testing (CPX). We determined their fat oxidation (FATox) by indirect calorimetry.

Results

In the HF patients, the peak oxygen uptake (VO2) value was 14.76 ± 3.27 ml/kg/min in the T2DM group and 17.76 ± 4.64 ml/kg/min in the non-T2DM group. After adjusting for age, sex, body mass index (BMI), log N-terminal pro-B type natriuretic peptide (log NT-proBNP), left ventricular ejection fraction (LVEF), hemoglobin, renal function, coronary heart disease and hypertension, the peak VO2 was lower in the T2DM group compared to the non-T2DM group with a mean difference (MD) of −2.0 ml/kg/min [95% confidence interval (CI), −3.18 to −0.82, P < 0.01]. The VO2 at anaerobic threshold (AT VO2) was also lower in the T2DM group than in the non-T2DM group, with a MD of −1.11 ml/kg/min (95% CI −2.04 to −0.18, P < 0.05). Regarding the fat oxidation capacity during CPX, the T2DM group's maximal fat oxidation (MFO) was lower than that of the non-T2DM group (0.143 ± 0.055 vs. 0.169 ± 0.061 g/min, P < 0.05). In addition, the T2DM group had lower FATox at exercise intensity levels of 40% (P < 0.05) and 50% (P < 0.05) of peak VO2, compared to the non-T2DM group.

Conclusions

T2DM is associated with a decrease in exercise tolerance and fat oxidation capacity in patients with heart failure. Thus, it could be useful to develop exercises of appropriate intensity to optimize physical and metabolic health.
The weight-adjusted-waist index predicts all-cause and cardiovascular mortality in hypertension
Authors: Zheng Yu , Nie Zixing , Zhang Yifan , Sun Tao
Published: February 2025

Background

Weight-adjusted-waist (WWI) is a novel indicator of obesity that reflects the degree of central obesity in the human body.

Objectives

The study aimed to explore the relationship between WWI and mortality in hypertensive individuals.

Methods

Cross-sectional data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES) dataset were used in this study. The relationship between WWI and mortality was assessed using a weighted Cox proportional risk model; the nonlinear relationship was explored using restricted cubic splines. The robustness of the results was verified by subgroup and sensitivity analyses.

Results

A cohort of 11,556 people with a diagnosis of hypertension was included in this study. As a continuous variable, WWI was linked to higher rates of mortality from all-cause (HR = 1.23, 95% CI = 1.14, 1.33) and cardiovascular disease (CVD) (HR = 1.43, 95% CI = 1.23, 1.66) with hypertension in Model 3 adjusted for variables. Using WWI as a tertile categorical variable, individuals in the highest tertile had a 33% higher risk of all-cause death (HR = 1.33, 95% CI = 1.14, 1.56) and a 65% higher risk of CVD death (HR = 1.65, 95% CI = 1.19, 2.27) than individuals in the lowest tertile. According to the subgroup analysis, almost all groups showed a consistent positive correlation between WWI and mortality related to all-cause and CVD.

Conclusion

In adults with hypertension, there is a positive association between WWI and all-cause and CVD mortality.
A smartphone-guided secondary prevention digital health application reduces systolic blood pressure in patients with chronic coronary syndrome and insufficient blood pressure control
Authors: Düsing Philip , Schirmer Stephan H. , Schäfer Sebastian , Krogmann Alexander , Sinning Jan-Malte , Werner Nikos , Bönner Florian , Sedaghat Alexander , Müller Cornelius , Eckardt Irina , Nickenig Georg , Zietzer Andreas
Published: February 2025

Background

Chronic coronary syndrome (CCS) leads to high morbidity and mortality despite therapeutic advances in recent decades. Several modifiable risk factors, including increased blood pressure (BP), significantly contribute to cardiovascular risk in CCS. Therefore, optimal secondary prevention includes managing BP through lifestyle changes and pharmacological therapy. The CHANGE study aimed to provide evidence for optimizing secondary prevention in CCS patients using a smartphone application.

Methods

The CHANGE-Study is a prospective, randomized, controlled trial performed in 9 centers in Germany. Patients with CCS were randomly allocated to either a control or an intervention group. The intervention group received the “Vantis | KHK und Herzinfarkt” digital health application and standard care. The control group received standard care alone. From the original cohort, subgroups of patients with systolic BP ≥140 mmHg (n = 44), ≥130 mmHg (n = 89) and diastolic BP ≥90 mmHg (n = 28) were analyzed for BP reduction after 12 weeks.

Results

In patients with systolic BP ≥140 mmHg, the intervention group showed a reduction in systolic BP by 15.5 mmHg (± 16.7 mmHg, p = 0.0001), which was greater compared to the control group (6.0 ± 13.0 mmHg, p = 0.058). This observation was consistent in patients with systolic BP ≥130 mmHg at baseline. No significant differences between both groups were observed in diastolic BP reduction in patients with diastolic BP ≥90 mmHg.

Conclusion

The CHANGE study documents that a smartphone-guided digital health application positively affects systolic BP in CCS patients. This study underlines the potential of digital interventions in cardiology to improve secondary prevention.
Association between pan-immune-inflammation value and coronary heart disease in elderly population: a cross-sectional study
Authors: Ma Ruicong , Ren Jinyi , Chen Xianmei , Li Xia , Zhao Ying , Ding Yanchun
Published: February 2025

Background

Systemic inflammation, immune and nutrition status are closely linked to the occurrence and development of coronary heart disease (CHD). Pan-immune-inflammation value (PIV) is a new method for evaluating systemic inflammation and immune status. Our objective is to explore the connection between PIV and CHD especially in elderly people, as well as the diagnostic value of PIV combined with controlling nutritional status (COUNT) score for CHD.

Methods

Participants eligible for the study were sourced from NHANES data from 1999 to 2018. Logistic regression models were employed to evaluate the link between PIV and CHD. Additionally, restricted cubic spline was utilized to explore the correlations. Subgroup analysis was adopted in order to ensure the credibility of the results. The receiver operator characteristic (ROC) curve was used to explore the predictive value of PIV combined with COUNT score for CHD.

Results

41,713 individuals qualified for analysis. The individuals with CHD had higher levels of PIV. In the logistic regression model, PIV was positively related to CHD [Q4 vs. Q1, OR = 1.23 (1.03–1.48, P < 0.001)]. Restricted cubic spline indicated a positive non-linear relationship (P for overall <0.001, P for non-linear = 0.009). However, restricted cubic spline shows that this positive correlation is only significant in the elderly population aged 60 and above. Subgroup analysis shows that the relationship between PIV and CHD is more significant in the elderly population (P < 0.001). The ROC curve shows that PIV has better diagnostic value for CHD than other common inflammatory indicators. Furthermore, the combination of PIV and COUNT score is superior to PIV or COUNT score.

Conclusions

A positive link between PIV and CHD, especially in the elderly. The combination of PIV and COUNT score has better diagnostic value for CHD.
Edge-level multi-constranint graph pattern matching with lung cancer knowledge graph
Authors: Tu Houdie , Li Lei , Tao Zhenchao , Zhang Zan
Published: February 2025

Introduction

Traditional Graph Pattern Matching (GPM) research mainly focuses on improving the accuracy and efficiency of complex network analysis and fast subgraph retrieval. Despite their ability to return subgraphs quickly and accurately, these methods are limited to their applications without medical data research.

Methods

In order to overcome this limitation, based on the existing research on GPM with the lung cancer knowledge graph, this paper introduces the Monte Carlo method and proposes an edge-level multi-constraint graph pattern matching algorithm TEM with lung cancer knowledge graph. Furthermore, we apply Monte Carlo method to both nodes and edges, and propose a multi-constraint hologram pattern matching algorithm THM with lung cancer knowledge graph.

Results

The experiments have verified the effectiveness and efficiency of TEM algorithm.

Discussion

This method effectively addresses the complexity of uncertainty in lung cancer knowledge graph, and is significantly better than the existing algorithms on efficiency.
Training and onboarding initiatives in high energy physics experiments
Authors: Reinsvold Hall Allison , Skidmore Nicole , Benelli Gabriele , Carlson Ben , David Claire , Davies Jonathan , Deconinck Wouter , DeMuth David , Elmer Peter , Garg Rocky Bala , Hageböck Stephan , Lieret Killian , Lukashenko Valeriia , Malik Sudhir , Morris Andy , Schellman Heidi , Stewart Graeme A. , Veatch Jason , Hernandez Villanueva Michel
Published: February 2025

In this article we document the current analysis software training and onboarding activities in several High Energy Physics (HEP) experiments: ATLAS, CMS, LHCb, Belle II and DUNE. Fast and efficient onboarding of new collaboration members is increasingly important for HEP experiments. With rapidly increasing data volumes and larger collaborations the analyses and consequently, the related software, become ever more complex. This necessitates structured onboarding and training. Recognizing this, a meeting series was held by the HEP Software Foundation (HSF) in 2022 for experiments to showcase their initiatives. Here we document and analyze these in an attempt to determine a set of key considerations for future HEP experiments.
Proximity extension assay revealed novel inflammatory biomarkers for follicular development and ovarian function: a prospective controlled study combining serum and follicular fluid
Authors: Wang Chong , Feng Ying , Chen Yu , Lin Xianhua , Li Xiangjuan
Published: February 2025

Background

Many components in follicular fluid (FF), such as peptide hormones, cytokines, and steroids, undergo dynamic changes during folliculogenesis and have important roles in follicular development. Because systemic inflammation has also been found to contribute to diminished ovarian reserve (DOR) in previous studies, do certain serum/FF inflammatory biomarkers affect both follicular development and ovarian function?

Methods

Serum samples from the menstruation phase (n=26), serum samples from the ovulation phase (n=26), FF samples of mature oocytes (n=26), and FF samples of immature oocytes (n=10) were collected. Olink proteomic proximity extension assay (PEA) technology was used to compare the differentially expressed proteins (DEPs), and patients were divided into two subgroups—the normal ovarian reserve (NOR) group and the DOR group—for further bioinformatics analysis and verification by enzyme-linked immunosorbent assay (ELISA).

Results

In total, 16 DEPs were detected between the mature group and the immature group (FF), and 11 DEPs were detected between the ovulation group and the menstruation group (serum). Further subdivision of the ovarian reserve subgroups revealed 22 DEPs in FF and 3 DEPs in serum. Among all four comparisons, only the expression of oncostatin M (OSM) significantly differed. The OSM signaling pathway, the IL-10 anti-inflammatory signaling pathway, and the PI3K−Akt signaling pathway are three notable pathways involved in affecting ovarian reserve capacity according to bioinformatics analysis. In addition, the concentration of estradiol on the hCG day was slightly but positively correlated with OSM (r=0.457, P=0.029). A significantly greater level of OSM (5.41 ± 2.65 vs. 3.94 ± 1.23 pg/mL, P=0.007) was detected in the serum of NOR patients via ELISA verification, and the sensitivity and specificity of ovarian reserve division were 50.00% and 83.33%, respectively.

Conclusion

This study proposed that immunological changes assessed by PEA technology affect ovarian function in humans and that OSM may serve as a potential inflammatory biomarker for ovarian function in serum, thus revealing alterations in FF.
Efficacy and safety of once-weekly semaglutide monotherapy in a young subject with Prader-Willi syndrome, obesity, and type 2 diabetes: a case report
Authors: Dinoi Elisa , Daniele Giuseppe , Michelucci Angela , Baldinotti Fulvia , Campi Fabrizio , Marchetti Piero , Del Prato Stefano , Dardano Angela
Published: February 2025

Background

The treatment of obesity and type 2 diabetes (T2D) in Prader-Willi syndrome (PWS) is still a challenge. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are attractive options, since they effectively reduce weight and improve blood glucose, without increasing the risk of hypoglycemia. However, data on their use in PWS are scarce.

Case description

In 2019, a 27-year-old male came to our Clinic because of first appearance of severe hyperglycemia (fasting plasma glucose 22.5 mmol/L). Based on clinical presentation, PWS was suspected, and diagnosis was confirmed by genetic tests. The patient was discharged on a basal-bolus insulin therapy managed by his parents due to his cognitive impairment. In spite of COVID-19 pandemic, the patient achieved tight glycemic control (HbA1c 41 mmol/mol) with non-severe hypoglycemic events in the face of significant body weight (BW) increase (+ 13 kg vs baseline). Insulin therapy was then discontinued, and once-weekly semaglutide (up to 0,5 mg weekly) was started. At 12-month follow-up, BW dropped from 79 to 73 kg while maintaining excellent glycemic control (HbA1c 40 mmol/mol). At 24-month follow-up, glycemic control remained optimal (HbA1c 38 mmol/mol) with further BW reduction (71 kg). Neither hypoglycemia nor gastro-intestinal or psychiatric adverse events were reported.

Conclusion

This case supports the potential use of semaglutide for the treatment of subjects with PWS, obesity and T2D. Ad hoc trials are needed to evaluate the long-term efficacy and tolerability in these subjects.
Digital financial inclusion and economic green growth: evidence from counties covered by China’s national key ecological functional zones
Authors: Mo Li , Chen Song , Wan Shenwei , Liang Chen , Ma Ye
Published: February 2025

Against the backdrop of growing attention being paid to both ecological compensation and the digital economy, this paper explores the impact of digital financial inclusion on green economic growth in counties within China’s National Key Ecological Functional Zones (NKEFZs) from 2014 to 2022, using panel data from 393 counties. Employing a two-way fixed-effects model, the study finds that digital financial inclusion promotes both traditional and green economic growth. The study results are robust, even after a series of robustness tests. The mechanisms identified include agricultural technology progress, industrial structure upgrading, and enterprise innovation and entrepreneurship. However, the effect is less significant in western and northeastern regions, as well as in windbreak and sand-fixing zones. The study highlights the potential of digital finance to help resource-rich, underdeveloped regions overcome the “resource curse” and foster sustainable economic growth.
Spatial analysis of measles cases and vaccination coverage in the Somali region, eastern Ethiopia
Authors: Muse Abdilahi Ibrahim , Kayat Mahdi Yonis , Aden Mohamed Harir , Shuramu Jemal Beksisa , Mohammed Shikur , Ibrahim Musse Ahmed , Berhe Binyam Mohammedbirhan , Kalinle Ahmed Abdi , Abdilahi Sahardiid Ali
Published: February 2025

Background

Measles is a major public health concern that causes morbidity and mortality among children. In 2019, measles incidence reached its highest level in 23 years, with low measles containing vaccine dose one coverage playing a vital role. It can be prevented by two doses of the measles vaccine, either alone or in combination with measles-rubella (MR), which is a low-cost strategy for lowering morbidity and mortality among children.

Objectives

To conduct spatial analysis of measles cases and vaccination coverage in the Somali region, Eastern Ethiopia.

Methods

This retrospective study was done by using public health emergency directorate measles data from 2022 to 2023 and four years (July 2019–July 2023) of vaccination data from district health information system version 2.36. After the data completeness and consistency were ensured, it was cleaned and recoded. STATA version 17 and QGIS version 3.38 software were used for the data analysis.

Results

From 2022 to 2023, the disease affected more than 5,930 people. The majority of the participants, 5,260 (88.7%), were under the age of 59 months, with 3,184 (53.7%) being male. Furthermore, the majority of residents were from Nogob 2,238 (37.7%), Erer 1,027 (17.3%), and Jarar 954 (16.1%). According to clinical symptoms, 5,930 (100%) of the cases had fever, cough, and rash, and more than two-thirds, 4,901 (82.6%), had complications. A measles vaccination coverage of 59.4% and a measles incidence of 0.087 per 100 people were found in the region.

Conclusions

This study found a very low measles vaccination coverage. Furthermore, Nogob, Erer, and Jarar zones showed the highest measles incidence rate, respectively. It is recommended to strengthen routine immunization services according to the national vaccination agenda, categorize, and reach unvaccinated children through catch-up vaccination campaigns. A concerted effort should be made to improve MCV2 coverage in hard-to-reach areas of the region. Special focus should be given to vaccine cold chain management in the zone and its districts with high vaccination coverage but also a high measles incidence rate. An investigation should be done into the associated factors of the higher incidence despite its vaccination coverage.
Predicting pregnancy loss and its determinants among reproductive-aged women using supervised machine learning algorithms in Sub-Saharan Africa
Authors: Yehuala Tirualem Zeleke , Mengesha Sara Beyene , Baykemagn Nebebe Demis
Published: February 2025

Background

Pregnancy loss is a significant public health issue globally, particularly in Sub-Saharan Africa (SSA), where maternal health outcomes continue to be a major concern. Despite notable progress in improving maternal health, pregnancy-related complications, including s due to miscarriages, stillbirths, and induced abortions, continue to impact women's health, social wellbeing, and economic stability in the region. This study aims to identify the key predictors of pregnancy loss and develop effective predictive models for pregnancy loss among reproductive-aged women in SSA.

Methods

We derived the data for this cross-sectional study from the most recent Demographic and Health Survey of Sub-Saharan African countries. Python software was used to process the data, and machine learning techniques such as Random Forest, Decision Tree, Logistic Regression, Extreme Gradient Boosting, and Gaussian were applied. The performance of the predictive models was evaluated using several standard metrics, including the ROC curve, accuracy score, precision, recall, and F-measure.

Result

The final experimental results indicated that the Random Forest model performed the best in predicting pregnancy loss, achieving an accuracy of 98%, precision of 98%, F-measure of 83%, ROC curve of 94%, and recall of 77%. The Gaussian model had the lowest classification accuracy, with an accuracy of 92.64% compared to the others. Based on SHPY values, unmarried women may be more likely to experience pregnancy loss, particularly in contexts where premarital pregnancies are stigmatized. The use of antenatal care and family planning services can significantly impact the risk of pregnancy loss. Women from lower-income backgrounds may face challenges in accessing prenatal care or safe reproductive health services, leading to higher risks of loss. Additionally, higher levels of education are often correlated with increased awareness of family planning methods and better access to healthcare, which can reduce the likelihood of unintended pregnancy loss.

Conclusion

The Random Forest machine learning model demonstrates greater predictive power in estimating pregnancy loss risk factors. Machine learning can help facilitate early prediction and intervention for women at high risk of pregnancy loss. Based on these findings, we recommend policy measures aimed at reducing pregnancy loss Sub-Saharan African countries.
Bibliometric analysis of targeted immunotherapy for osteosarcoma-current knowledge, hotspots and future perspectives
Authors: Hu Yunxiang , Yang Rui , Ni Shuai , Song Zefeng
Published: February 2025

Objective

The objective of this study is to conduct a bibliometric analysis on examining the current condition, areas of interest, and rising trends of immunotherapy for osteosarcoma (ITFOS), as well as its importance in associated research domains.

Methods

An extensive collection of academic papers on the use of ITFOS was obtained from the Web of Science between January 1, 2000 and October 20, 2023. Then, using a variety of tools like HisCite, VOSviewer, CiteSpace, and the bibliometrix package, a bibliometric study was carried out. This study included the collection of information on country, institution, author, journal, and keywords.

Results

A comprehensive analysis was undertaken on a total of 616 publications obtained from 247 journals, encompassing the contributions of 3725 authors affiliated with 831 institutes spanning across 43 countries/regions. Notably, China exhibited the highest quantity of published 277 (44.99%) articles on ITFOS. The most productive institution was Zhejiang University, with 26 (4.22%) publications. The author with the highest publication output was Tsukahara, Tomohide from Japan with 15 (2.44%) publications. The article with the most citation was “DOI: 10.1200/JCO.2014.58.0225”. Frontiers in Immunology demonstrated the highest level of productivity, having published a total of 31 (5.03%) articles. The most frequently used were “osteosarcoma,” “immunotherapy,” and “cancer,”. Meanwhile, “sequencing”, “prognostic signature” and “immune microenvironment“ have been identified as the research frontiers for the forthcoming years.

Conclusion

This paper provides a thorough evaluation of current research trends and advancements in ITFOS. It includes relevant research findings and emphasizes collaborative efforts among authors, institutions, and countries.
Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy
Authors: De Lucia Anna , Mazzotti Lucia , Gaimari Anna , Zurlo Matteo , Maltoni Roberta , Cerchione Claudio , Bravaccini Sara , Delmonte Angelo , Crinò Lucio , Borges de Souza Patricia , Pasini Luigi , Nicolini Fabio , Bianchi Fabrizio , Juan Manel , Calderon Hugo , Magnoni Chiara , Gazzola Luca , Ulivi Paola , Mazza Massimiliano
Published: February 2025

Over the past decades, significant progress has been made in the understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting in the development of novel strategies for early detection and wide-ranging care approaches. Since their introduction, over 20 years ago, targeted therapies with tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for NSCLC. Nowadays, targeted therapies remain the gold standard for many patients, but still they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance mutations, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits for patients without targetable alterations. Despite this notable progress, challenges remain, as not all patients respond favorably to ICIs, and resistance to therapy can develop over time. A crucial factor influencing clinical response to immunotherapy is the tumor microenvironment (TME). The TME is pivotal in orchestrating the interactions between neoplastic cells and the immune system, influencing tumor growth and treatment outcomes. In this review, we discuss how the understanding of this intricate relationship is crucial for the success of immunotherapy and survey the current state of immunotherapy intervention, with a focus on forthcoming and promising chimeric antigen receptor (CAR) T cell therapies in NSCLC. The TME sets major obstacles for CAR-T therapies, creating conditions that suppress the immune response, inducing T cell exhaustion. To enhance treatment efficacy, specific efforts associated with CAR-T cell therapy in NSCLC, should definitely focus TME-related immunosuppression and antigen escape mechanisms, by combining CAR-T cells with immune checkpoint blockades.
Efficacy of natural killer T and gammadelta T cells in mesothelin-targeted immunotherapy of pancreatic cancer
Authors: Zhu Yuankui , Yang Yaxi , Yue Linghe , Wan Lei , Ma Xuqian , Yang Qing , Tian Xuan , Li Yuguan , Wang Ke , Wei Shaozhong , Zuo Dianbao , Feng Mingqian
Published: February 2025

Current pancreatic cancer immunotherapy focused on alphabeta (αβ) T cells, either through CD3-engaged bispecific antibodies or CAR-T. Despite their promise, dose-limited toxicity (DLT) remains a challenge in clinical practice. In light of these concerns, there is a growing interest in exploring alternative T cell types, natural killer T (NKT) cells and gammadelta (γδ) T cells, that possess the capacity to lyse tumors while potentially offering a safer therapeutic profile with fewer side effects. These cells present a compelling alternative that warrants a comprehensive evaluation of their therapeutic potential and safety profile. This study employed a MSLN/CD3 bispecific antibody to compare the anti-tumor activity of NKT and γδT cells with peripheral blood mononuclear cells (PBMCs) as controls, both in vitro and in vivo. This study demonstrated that MSLN/CD3 BsAb effectively activated and recruited PBMCs, NKT and γδT. Furthermore, under the influence of MSLN/CD3 BsAb, γδT and NKT cells exhibited notably superior anti-tumor activity compared to PBMCs, both in vitro and in vivo, while demonstrating low cytokine release. γδT cells showed almost negligible toxic side effects. In addition, the systemic administration of NKT and γδT cells activators, α-galactosylceramide (α-GalCer) and Zoledronate, could enhance the anti-tumor effect of MSLN/CD3 bsAb, with no apparent toxicity. NKT and γδT cells are promising synergistic therapeutic cell types that may overcome the limitations of CD3 bispecific antibodies in pancreatic tumor treatments, offering a new perspective for clinical applications in immunotherapy.
Association of high-sensitivity C-reactive protein with hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease
Authors: Wu Yunfei , Zheng Guojun , Zhang Fan , Li Wenjian
Published: February 2025

Objective

This study aimed to investigate the association between high-sensitivity C-reactive protein (hsCRP) levels and hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and assess its predictive efficacy.

Methods

The study included 1,477 participants from the United States and 1,531 from China diagnosed with MASLD. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the presence and degree of hepatic fibrosis and steatosis. The relationship between hsCRP levels and hepatic fibrosis in MASLD patients was examined using multivariable-adjusted and restricted cubic spline (RCS) models. Additionally, subgroup analyses were conducted to investigate the potential heterogeneity among different characteristic subgroups.

Results

The results demonstrated a significant correlation between elevated hsCRP levels and an increased risk of significant fibrosis, advanced fibrosis, and cirrhosis in the US cohort of MASLD patients (OR 2.22, 1.69, and 2.85, respectively; all P <0.05). The results of the Chinese cohort were consistent with those of the US cohort, and there was a significant and positive correlation between hsCRP levels and the risk of hepatic fibrosis in patients with MASLD (OR 2.53, 3.85, and 3.78, respectively, all P <0.001). The RCS analysis revealed a significant non-linear relationship between hsCRP levels and the degree of hepatic fibrosis, with disparate inflection point values observed across different cohorts (approximately 9 mg/L in the US cohort and 4 mg/L in the Chinese cohort). The impact of hsCRP levels on the risk of hepatic fibrosis varied across different subgroups with distinct characteristics.

Conclusion

The present study demonstrated a significant correlation between hsCRP levels and the degree of hepatic fibrosis in patients with MASLD, with notable dose-response relationships and subgroup differences.
Synthesis of PVA-based macromolecular photoinitiators through esterification with TXOCH₂COOH and cysteine, and investigation of their photophysical properties: in situ fabrication of flexible nanocomposite films
Authors: Konar Melisa , Nakamura Kazuki , Arsu Nergis
Published: February 2025

2-(Carboxymethoxy) thioxanthone (TX-OCH₂COOH), a thioxanthone derivative, was utilized for the esterification of polyvinyl alcohol (PVA) to synthesize a macromolecular photoinitiator, both in the absence and presence of Cysteine (Cys). The covalent attachment of the thioxanthone (TX) group to PVA through esterification enabled the exploration of the photophysical properties of the resulting macromolecular photoinitiators (TXOCH₂COO-PVA and TXOCH₂COO-PVA-Cys) via UV-Vis and fluorescence studies. UV-Vis absorption spectrum of TXOCH₂COO-PVA confirmed the covalent bonding of TX, marked by a characteristic absorption peak at 397 nm corresponding to the thioxanthone chromophore. Fluorescence lifetimes were recorded as TXOCH₂COO-PVA was cast into a mold and air dried, resulting in a flexible form of PVA esterified with TXOCH₂COOH. In-situ synthesis of both silver and selenium nanoparticles was carried out using both TXOCH₂COO-PVA and TXOCH₂COO-PVA-Cys macromolecular initiators, successfully yielding nanocomposite flexible polymeric films.
Diagnostic efficacy and necessity of 18F-FDG PET/CT in fever of unknown origin: insights from a retrospective cohort study
Authors: Yu Xiaoman , Wang Shuang , Du Na , Zhao Hongguang , Chen Haiying
Published: February 2025

Background

Despite advancements in medical examination equipment and techniques, fever of unknown origin (FUO) remains challenging in internal medicine.

Purpose

This study evaluates the diagnostic efficacy and necessity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with FUO.

Methods

We retrospectively analyzed the results of 18F-FDG PET/CT in a cohort of 284 patients with FUO admitted to the Department of Infection at the First Hospital of Jilin University between January 2018 and March 2024. All patients received a final clinical diagnosis after various treatments, which helped determine the diagnostic relevance of identified lesions using 18F-FDG PET/CT. Additionally, univariate and multivariate logistic regression analyses were performed to evaluate the predictive value of relevant laboratory indices on the true-positive results of 18F-FDG PET/CT. The diagnostic performance for different etiologies of FUO was assessed by calculating the area under the receiver operating characteristic curve.

Results

Of the 284 enrolled patients, infectious diseases were diagnosed in 53 (18.7%), non-infectious inflammatory diseases in 76 (26.8%), malignant tumors in 66 (23.2%), and 89 (31.3%) remained undiagnosed. The final diagnoses of 136 patients (47.9%) correlated with their 18F-FDG PET/CT results, yielding a sensitivity of 79.5%, specificity of 61.1%, positive predictive value of 75.6%, and negative predictive value of 66.3%. Furthermore, a correlation was found between localized pain, prolonged activated partial thromboplastin time, and true-positive 18F-FDG PET/CT results.

Conclusion

The high diagnostic efficacy of 18F-FDG PET/CT in FUO suggests its potential as a routine imaging modality, which could enhance patient management and reduce the need for costly and unnecessary invasive procedures. The identification of clinical factors that are predictive of true-positive diagnosis could facilitate more effective allocation of PET/CT imaging.
Efferocytosis and inflammation: a bibliometric and systematic analysis
Authors: Cao Xin , Li Fen , Xie Xi , Ling Guanghui , Tang Xiaoyu , He Wenfang , Tian Jing , Ge Yan
Published: February 2025

Objective

To visualize and analyze the trends and hotspots of efferocytosis and inflammation via bibliometric methods.

Methods

Relevant articles and reviews from 2006 to 2023 were retrieved from the Web of Science Core Collection. The data were processed with CiteSpace, and some graphs were generated with Microsoft Excel (version 2016), VOSviewer, Scimago Graphica, Bibliometrix and R Studio.

Results

A total of 1,003 papers were included, revealing a significant upward trend in efferocytosis and inflammation research. The United States (456, 45.46%), China (164, 16.35%) and the United Kingdom (99, 9.87%) were the three countries with the highest numbers of publications. Harvard University (84, 6.74%) contributes the most out of the top 5 institutions. Among the researchers in this field, Serhan CN was the author with the highest number of articles in the field (35, 3.49%), and deCathelineau AM first named “efferocytosis” in 2003. Keyword analysis identified “activation,” “tam receptors,” “docosahexaenoic acid” “systemic lupus erythematosus,” “myocardial infarction” and “alveolar macrophages” as core topics, indicating a concentrated trend in the mechanism of physiological state and inflammatory diseases such as autoimmune, cardiovascular, and pulmonary diseases. The latest surge words “inflammation resolution” and “cancer” in the keyword heatmap indicate future research directions.

Conclusion

Research on the association between efferocytosis and inflammation has been a promising field. Key areas of focus include the crucial role of efferocytosis on tissue homeostasis and the pathogenesis of nontumorous inflammatory diseases. Future research will likely continue to explore these frontiers, with an emphasis on understanding efferocytosis in the context of chronic diseases and cancer, as well as developing novel therapeutic strategies.
A vacuum lyophilization and bacterial tablet-based method for culture medium evaluation and potential use in probiotic products
Authors: Cui Wen , Zhao Liang , Shi Yuwen , Feng Wei , Chen Xiao , Liu Hui
Published: February 2025

Introduction

The fundamental step in microbiological detection is the preparation of culture medium. The reliability and accuracy of microbiological assay heavily relies on this step. Currently in China, the most recognized standard method for such medium evaluation is ISO 11133-2014. However, this method requires highly complicated biosafety management, detailed standard strains record-keeping and substantial working time.

Methods and results

Bacterial tablet is considered to be a novel strategy for bacteria culture medium evaluation. The filter membrane as a carrier ensures uniform cell dispersion, forming a singular colony that can facilitate counting. We examined the viability and storage durability of vacuum freeze-dried bacterial tablets using a filter membrane as a carrier and utilized the results to evaluate culture medium. We found that the recipe GBSS (Glycerinum, Brain Heart Infusion, Sucrose, Sodium Glutamate) showed the highest survival rate for Escherichia coli in vacuum freeze-drying. As a qualified medium, the productivity of target bacterium should be greater than 0.7. A comparison of freeze-dried bacterial tablet method with ISO 11133-2014 quantitative method showed the sensitivity and specificity of this novel method were 94.1% and 88.9% respectively. The results suggested that vacuum freeze-dried bacterial tablet method had high conformity when compared to ISO 11133-2014 quantitative method (χ2 = 0.25, p > 0.05; Kappa = 0.75).

Discussion

Hence, vacuum freeze-drying method is an integral part of preservation of bacterial strains and the preparation of related biological products. In conclusion, we have developed a novel and effective disposable product for estimating efficiency of the culture medium.
Cassava–soybean intercropping alleviates continuous cassava cropping obstacles by improving its rhizosphere microecology
Authors: Chen Huixian , Ruan Lixia , Cao Sheng , He Wen , Yang Haixia , Liang Zhenhua , Li Hengrui , Wei Wanling , Huang Zhenling , Lan Xiu
Published: February 2025

Introduction

Continuous cropping is the main cause of cassava yield reduction. To find an effective method to alleviate the obstacle of cassava continuous cropping and explore the effect of cassava–soybean intercropping, this study analysed the differences in cassava agronomic traits, yield, soil physicochemical properties, microbial community structure, and metabolites between cassava single cropping (M) and cassava–soybean intercropping (MD) and its effects on continuous cassava cropping soil.

Methods

The correlations between yield, agronomic traits, soil physicochemical properties, microbial diversity, and metabolites were explored, and the effect of the cassava–soybean intercropping model on cassava soil was revealed.

Results

The results showed that compared with group M, soil pH, porosity, organic matter, available nitrogen, and fresh potato yield in the MD group significantly increased by 8.59, 13.66, 20.68, 23.29, and 50.61%, respectively, and soil bulk density significantly decreased by 9.68%. Soil bacterial community diversity in the MD group did not change significantly but had significant effects on soil fungal community diversity. The relative abundances of Trichoderma and Micropsalliota in the MD group were significantly upregulated. The contents of phenol glucuronide, 2,3-butanediol, L-phenylalanine, deoxyguanosine, other carbohydrates, alcohols, purine nucleotides, and amino acids in the soil of the MD group were significantly upregulated. Organic acids, such as fumaric acid, succinic acid, phosphoenolpyruvic acid, decreased significantly. Correlation analysis showed that Trichoderma was significantly negatively correlated with fumaric acid, succinic acid, phosphoenolpyruvic acid, and soil bulk density. However, there was significant positive correlation with phenol glucuronide, alpha-CEHC deoxyguanosine and other carbohydrates, nucleotide substances, organic matter, and pH. Phenol glucuronide, 2,3-butanediol, L-phenylalanine, deoxyguanosine and other carbohydrates, alcohols, purine nucleotides, and amino acids were significantly positively correlated with organic matter, available nitrogen, soil porosity, and pH.

Discussion

Therefore, cassava–soybean intercropping can effectively alleviate the obstacles of continuous cassava cropping by affecting the accumulation of metabolites and microbial community structure in continuous cropping soil, thereby improving the adverse factors of severe soil acidification, soil compaction, and nutrient decline.
iPSC-derived exosomes as amphotericin B carriers: a promising approach to combat cryptococcal meningitis
Authors: Zhao Jingyu , Fang Wei , Gao Yangjie , Chen Jiquan , Wang Guizhen , Gu Julin
Published: February 2025

Background

Cryptococcal meningitis (CM) is a significant global health issue, particularly affecting individuals with HIV. Amphotericin B (AmB) serves as the cornerstone treatment for CM; however, its clinical application is restricted due to limited penetration of the blood–brain barrier and associated nephrotoxicity.

Objective

This study investigates the use of exosomes derived from induced pluripotent stem cells (iPSC-Exos) as carriers for AmB in treating CM, aiming to enhance therapeutic efficacy and safety and reduce AmB toxicity.

Methods

Exosomes were extracted from iPSC culture supernatants using ultrafiltration and ultracentrifugation. Their morphology and size were analyzed using transmission electron microscopy (TEM) and nanoparticle flow cytometry (nFCM). Purity was confirmed by Western blotting for markers CD9, CD63, and TSG101. AmB was loaded into iPSC-Exos using a co-incubation method. The cytotoxicity of the iPSC-Exo/AmB complex was evaluated on HEK 293 T and RAW264.7 cells using the CCK-8 assay, while apoptosis was assessed using live/dead cell staining and flow cytometry. The hemolytic effects were tested using rabbit red blood cells. In a C57BL/6 J mouse model of cryptococcal infection, treatment groups (AmB, iPSC-Exo/AmB, and iPSC-Exo) were administered corresponding drugs, with blood and brain samples collected for analysis. The minimum inhibitory concentration (MIC) of iPSC-Exo/AmB and conventional AmB against Cryptococcus was determined.

Results

The iPSC-Exo/AmB complex exhibited reduced cytotoxicity in vitro and decreased AmB-induced renal and hepatic toxicity in vivo. Its MIC against Cryptococcus was over eight times lower than conventional AmB, significantly reducing fungal burden in the mouse brain and lowering serum inflammatory factors.

Conclusion

The iPSC-Exo/AmB complex is a promising therapeutic strategy that enhances AmB efficacy while reducing toxicity, offering new hope for treating CM and other refractory fungal infections of the central nervous system.
Effects of continuous cropping on bacterial community diversity and soil metabolites in soybean roots
Authors: An Liwei , Lu Xinnan , Zhang Pengyu , Sun Jiayao , Cong Baiming , Sa Rula , He Dexin
Published: February 2025

The alternating planting of corn and soybeans is regarded as an effective strategy in addressing the challenges faced in soybean cultivation. However, the precise mechanisms that control the bacterial microbiome in soybean roots in the soil, particularly in continuous cropping and rotational corn–soybean farming rotations, are remain unclear. This study employed both field and pot positioning experiments, using high-throughput and generic metabolomics sequencing techniques to explore the dynamics between soybean plants, root microflora, and soil metabolites, especially in the context of continuous cropping and fluctuating corn–soybean crop rotation. The process that included rotating corn soybeans significantly enhanced their grain yield, dry weight, soil nitrogen concentration, urease activity, as well as the accumulation of nitrogen, phosphorus, and potassium in various plant organs, compared to the traditional practice of continuous soybean cultivation. There is a significant reduction in the transit of bacterial operational taxonomic units (OTUs) from the rhizosphere to the endosphere through rhizoplane. The number of bacterial OTUs that are consumed and enriched on rhizoplane is greater than those that are enriched and absorbed in the endosphere. Continuous cropping practices significantly boost Burkholderiales, whereas chloroplast microorganisms significantly improve crop rotation techniques. Soil environmental factors, such as urease and accessible phosphorus, are crucial in establishing the relative prevalence of Rhodanobacter and other bacterial groups. Soil metabolites, such as benzyl alcohol, show a positive correlation with Cyanobacteria, while acidic compounds, such as D-arabinitol, are positively linked with Burkholderiales. This study indicates that the rotation of corn and soybean crops facilitates the growth of soybeans, increases nutrient accumulation in both plants and soil, enhances the presence of beneficial bacteria, and improves soybean yields.