bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies against tick-borne pathogens
Authors:   , Bakker Berendina Johanna Adriana
Published: February 2025

Climate change has expanded tick habitats, leading to greater human exposure to ticks and the pathogens they carry, especially in areas where nature-preserving activities like reforestation and urban greenspaces create overlapping habitats. In Northern Europe, Ixodes ricinus is the most prevalent tick species, known for transmitting Borrelia burgdorferi s.l., the causative agent of Lyme borreliosis (LB). In the Netherlands, LB is the most common vector-borne disease, with its incidence quadrupling since the 1990s. Other known I. ricinus-borne pathogens, including Anaplasma phagocytophilum, Babesia species, and Rickettsia helvetica, are emerging. Little is known about their epidemiology, which requires further study. The dissertation has two main objectives: (i) evaluating the performance of commercially available antibody assays and test strategies for LB diagnosis and their clinical interpretation, and (ii) assessing the prevalence of human antibodies against tick-borne pathogens and associated risk factors in various populations.
The main conclusions of part I of this dissertation were that commercially available assays and test strategies perform comparably well. While IgG or combined IgM/IgG assays and strategies showed high sensitivity and acceptable specificity, the added value of IgM testing is debatable. Despite advancements in serological testing, a reliable marker for active LB is still lacking, emphasizing the importance of interpreting laboratory results in the context of clinical history. A survey among medical microbiologists in the Netherlands revealed challenges in diagnosing active disease for low-incidence Lyme manifestations, suggesting the need for continued education. Artificial intelligence-guided algorithms and a case register could aid clinical decision-making, resulting in optimized diagnostic accuracy and increased patient trust.
In part II, a study of 2016/2017 data found a 4.4% prevalence of B. burgdorferi s.l.-specific antibodies in the general population, with higher rates in men, older individuals, and those with frequent tick bites. Comparisons with 1995/1996 data showed a significant increase in seroprevalence over time, particularly among those over 50, possibly due to increased outdoor activities. A cohort of nature management workers showed higher seropositivity rates for B. burgdorferi s.l. and demonstrated exposure to non-borrelial pathogens, indicating occupational exposure risks. Future research should focus on identifying reliable markers for active LB and developing state-of-the-art diagnostics for rare pathogens. Continued surveillance and diagnostic development are crucial for understanding the epidemiology and pathology of tick-borne diseases, ultimately aiding in disease prevention and burden reduction.
The effects of running shoe stack height on running style and stability during level running at different running speeds
Authors: Kettner Cagla , Stetter Bernd , Stein Thorsten
Published: February 2025

The footwear market contains a wide variety of running shoe solutions aiming at optimizing performance and minimizing injuries. Stack height is one of the most highly discussed design features of running shoes, but its effects are not yet well understood. This study investigated the effects of different shoes differing mainly in their stack heights (High: 50 mm, Medium: 35 mm and Low: 27 mm) on running style and stability during treadmill running at 10 and 15 km/h. A total of 17 healthy experienced runners participated. The kinematic data were recorded with a 3D motion capturing system. The running style was investigated with duty factor (DF) and leg length normalized to step frequency (SFnorm). Additionally, the ratio of landing to take-off duration, the lower body joint angle time series in the sagittal and frontal planes, the vertical center of mass oscillation (COMosc), and the stiffness parameters (kver and kleg) were compared for different conditions. The stability was analyzed using linear (i.e., discrete frontal ankle parameters) and nonlinear methods (i.e., Maximum Lyapunov Exponent for local dynamic stability of head, trunk, hip, and foot, and detrended fluctuation analysis of stride time). High resulted in longer ground contact relative to stride time (i.e., DF) compared to Low. The higher the stack height, the higher was the COMosc. Furthermore, High led to a longer foot eversion during stance compared to Medium. In addition, the local dynamic stability of the hip decreased with High in comparison with Low. The higher stack heights (≥35 mm) led to a lower SFnorm at 15 km/h but not at 10 km/h. The remaining shoe effects were independent of running speed. Findings showed that changes in stack height can affect running style. Furthermore, the highest stack height resulted in changes related with instabilities (i.e., longer foot eversion and lower hip dynamic stability) which may be a critical issue in terms of injuries and performance. However, this study did not include joint load analysis or running performance measures such as VO2. Future studies may benefit from combination of analysis approaches to better understand stack height effects on running injuries and performance.
Projections of population exposure to hot and dry events in the end of the 21st century on the Iberian Peninsula
Authors: Bento Virgílio A. , Lima Daniela C. A. , Russo Ana
Published: February 2025

The Iberian Peninsula (IP) is anticipated to undergo future shifts in precipitation patterns and an increased occurrence of hot and dry extreme (HDE) weather events, including droughts and heatwaves. Such events pose substantial risks to the region’s population and ecosystems, particularly amidst evolving demographic dynamics marked by an overall population decrease and contrasting growth in urban areas. This study evaluates population exposure to HDEs in the IP, comparing projected conditions for the late 21st century with the historical period (1971–2000). The Standardized Precipitation-Evapotranspiration Index (SPEI) is used to quantify droughts’ duration and the number of warm months to assess the frequency of extreme heat events. Two representative concentration pathways (RCPs), specifically RCP4.5 and RCP8.5, are considered to represent distinct greenhouse gas emission scenarios. This research reveals a significant projected increase in population exposure to both drought and warm months across the entire IP by the century’s end, with climate change identified as the primary driver of this escalation. Certain regions will experience a particularly drastic surge in drought exposure, while exposure to warm months may exceed 500% in some cases. Climate change’s impact on exposure surpasses that of population change, and the interplay between climate and population changes predominantly contributes negatively across all Iberian regions. These findings are expected to provide valuable insights for policymakers, planners, and stakeholders, guiding the development of targeted adaptation strategies and resource allocation. This proactive approach aims to enhance the resilience of vulnerable communities and ecosystems in response to the evolving climatic conditions.
Studies of three dimensional stagged-grid finite difference for Z-axis tipper electromagnetic numerical simulation
Authors: Wang Yu , Qu Junhao , Chen Tingting , Zhou Shaohui , Li Yajun
Published: February 2025

ZTEM (Z-Axis Tipper Electromagnetic System) is a frequency-domain airborne electromagnetic exploration method that utilizes natural field sources. This method is highly efficient and capable of probing great depths, making it widely applicable in the exploration of polymetallic mineral deposits. However, large-scale 3D forward modeling faces computational challenges due to the increase in data volume. This study employs the Aggregation-based Algebraic Multigrid (AGMG) and staggered grid finite-difference methods to achieve rapid solutions for three-dimensional ZTEM problems. The study shows that the AGMG-CG algorithm requires fewer iterations and achieves faster solutions, significantly enhancing computational speed, especially for large-scale 3D forward modeling problems. By analyzing the forward response characteristics of ZTEM, we show that tipper data accurately reflect lateral electrical interfaces. Furthermore, through extensive model testing, we analyze the main factors influencing the forward response of ZTEM. The study reveals that topographical variations may produce false anomalies, that a reasonable data acquisition bandwidth is crucial for identifying anomalies at different depths, and that low-altitude flights yield better responses.
Sedimentary microfacies prediction based on multi-point geostatistics under the constraint of INPEFA curve
Authors: Wang Xudong , Yang Zicheng , Liu Xibao , Yuan Chengyuan
Published: February 2025

The D Oilfield in the Songliao Basin has entered a critical phase of hydrocarbon exploration targeting the Quantou Formation. However, challenges persist in achieving precise stratigraphic division, sedimentary cycle characterization, and microfacies prediction. This study aims to enhance stratigraphic resolution and prediction accuracy of sedimentary microfacies to address uncertainties in sand body distribution within dense well pattern areas. Integrated Pattern Recognition and Fuzzy Analysis (INPEFA) was applied to natural gamma logging data from 4,215 wells, combined with maximum entropy spectrum attribute analysis (MESA) for high-precision sequence interface identification. Multi-point geostatistical simulations were implemented using well data and INPEFA-derived sequence stratigraphic frameworks. High-order compatibility algorithms constrained the simulations, with iterative human-computer interaction refining sedimentary microfacies models for three sand groups. Three distinct sedimentary phases were resolved: (1) Sand Group III exhibits rapid water encroachment with narrow, strip-like sand bodies; (2) Sand Group II records gradual lacustrine regression, forming extensive sheet-like sands; (3) Sand Group I reaches maximum flooding conditions, displaying laterally continuous sand bodies with intensified fluvial dynamics. The method predicts sedimentary microfacies under INPEFA curve constraints, which makes sequence interface identification more intuitive and improves cycle division and correlation precision. This multi-point geostatistics-based prediction image accurately reproduces river channel distribution patterns, offering high predictability and presenting a novel approach to characterizing fine sand bodies. This integrated approach not only predicts sedimentary microfacies distribution in dense well pattern areas of the Songliao Basin, but also presents a novel solution to the challenging geological problem of accurately forecasting effective sand body distribution. Furthermore, it provides critical stratigraphic evidence for developing remaining oil potential strategies in the basin, while offering an innovative methodology for reservoir characterization in other mature exploration regions worldwide.
Association of systemic immune inflammation index with depression among adult type 2 diabetic patients in a tertiary hospital, Ethiopia, 2022
Authors: Ali Seid Yimam , Sadik Mohammed Ibrahim , Seid Ahmed Muhye , Mohammed Awol Hassen , Yimam Ahmed Adem , Shegere Mekonin Meskelu , Shimels Ayele Tesfaneh , Wako Abdulmalik Jeben , Ibrahim Mohamedaman Mohamedsied
Published: February 2025

Background

The inflammatory and hormonal aspects of T2DM can influence the development or worsening of depressive symptoms. While most of the burden had due consideration, the mental health impact of T2DM such as depression is often unnoticed, undiagnosed, or untreated. Despite some studies exploring depression in Ethiopian T2DM patients, none have investigated the predictive role of the Systemic Immune inflammation Index (SII) in depression.

Objective

This study aimed to determine the prevalence of depression and its association with the Systemic Immune Inflammation Index (SII), socio-economic factors, and behavioral predictors among adult T2DM patients at Jigjiga University Comprehensive Specialized (JJU CS) Hospital.

Methods and materials

A hospital-based cross-sectional study was conducted from Oct 3 to Nov 13/2022 at JJUSH. Depression was assessed by using the Patient Health Questionnaire (PHQ-9). A complete blood count was done to calculate SII. Data entry was conducted using Epidata version 4.6 and subsequently analyzed in SPSS-V-26. Multiple logistic regression with the backward elimination method was performed. Variables with a p-value < 0.05 were considered statistically significant at a 95% CI

Results

A total of 263 T2DM patients were recruited in the study. Of these, 134 individuals (51%) were male. The overall prevalence of depression was 47.1%. Of the 263 enrolled T2DM patients, the majority, 142 (54%) had elevated SII. A multivariable logistic regression analysis indicated that high SII (AOR= 2.76), current Khat chewers (AOR= 2.83), ex-Khat chewers (AOR= 4.12), and female sex (AOR= 2.68) were identified independent predictors of depression.

Discussion

There was a high prevalence of depression among T2DM patients on follow-up at JJUSH. As well, SII, Khat chewing, and female sex were identified as predictors of depression. Therefore, relevant stakeholders should work towards control of systemic inflammation, avoidance of risky behaviors such as khat chewing, and promotion of healthy behavior particularly among females.
The triglyceride–glucose index is a promising predictor for the risk of cardiovascular disease in the diabetic population aged ≥60 years in the United States: a retrospective cohort study from NHANES (2007-2016)
Authors: Yang Shu , Wang Zhenwei
Published: February 2025

Background

The predictive value of triglyceride-glucose index (TyG) for cardiovascular disease (CVD) in the US elderly diabetic patients is ambiguous. This study aimed to investigate the association between TyG index and the risk of CVD in an older US population with diabetes.

Methods

The study examined data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Univariate and multivariate regression analysis models were obtained to explore the association between baseline TyG index and the risk of CVD. Non-linear association were investigated using restricted cubic spline (RCS) regression. Subgroup analyses and interaction tests were constructed and a sensitivity analyses was carried out. The 10 - year CVD risk were evaluated via the Framingham Risk Score (FRS). Mediation analysis explored the mediating role of glycated hemoglobin in the above relationships.

Results

A total of 2987 subjects were included (977 CVD patients and 2010 non-CVD persons). CVD patients had higher TyG values (9.01 ± 0.58 vs. 8.94 ± 0.56, P=0.003), and the prevalence of CVD increased with TyG index (P=0.015). In a multifactorial regression model with gradual adjustment for all covariates, the risk of CVD associated with TyG increased by 48.0% in the highest quartile group (OR 1.480, 95% Cl 1.171-1.871, P=0.001). The RCS curves showed a U-shaped association between TyG index and CVD risk (P for overall=0.013, P for nonlinear=0.043). Subgroup analyses showed that in the highest quartile group, individuals with body mass index (BMI) ≥24 kg/m2, an estimated glomerular filtration rate (eGFR) <90 mL/1.73m2/min, individuals without chronic kidney disease, and those with hypertension had significantly higher risks of CVD. Sensitivity analyses indicated that these associations were not associated with other significant confounders. Under different adjustment models, the TyG index exhibited significant correlations with the 10 - year risk of CVD (all P values < 0.05). Glycated hemoglobin mediated in the above relationships.

Conclusion

In a sample of US elderly diabetic patients, there is the U-shaped association of TyG index with CVD risk. This implies that TyG index can be regarded as an extremely important predictor for screening people at high risk of cardiovascular disease among elderly diabetic patients.
Prognostic analysis of esophageal cancer patients after neoadjuvant therapy
Authors: Dong Jing , Li Cheng , Wang Bingxiang , Li Yang , Wang Suzhen , Cui Hongxia , Gao Min
Published: February 2025

Background

Neoadjuvant therapy is widely used for esophageal cancer (EC), but optimal treatment regimens and predictive factors for outcomes remain unclear. This study retrospectively analyzed data from EC patients who underwent neoadjuvant therapy.

Methods

The chi-square test or Fisher’s exact test was utilized to examine differences in general clinicopathological data between treatment benefit groups. Survival analyses were conducted using Kaplan-Meier methods. Cox univariate and multivariate regression analyses were employed to identify independent risk factors affecting overall survival (OS) in EC patients receiving different treatment modalities.

Results

The study included 175 EC patients who underwent neoadjuvant therapy. Analysis of clinical benefit differences revealed that patients aged < 65 years (P = 0.028) and those with esophageal squamous cell carcinoma (ESCC) (P = 0.027) were more likely to achieve a complete response, while N1 patients more frequently attained an objective response (P < 0.001). OS analysis indicated that patients who did not receive immunotherapy exhibited better survival outcomes compared to those who did (P = 0.002). Patients with pretreatment N3 status demonstrated poorer survival compared to those with N0 (P = 0.004), N1 (P = 0.003), and N2 (P = 0.003) status. Among post-neoadjuvant EC patients who did not receive immunotherapy, those with primary tumors located in the middle esophagus (hazard ratio [HR], 0.181; 95% Confidence interval (CI) = 0.044-0.739; P = 0.017) and lower esophagus (HR, 0.163; 95%CI = 0.032-0.821; P = 0.028) demonstrated a better prognosis compared to patients with tumors in the upper esophagus. Notably, EC patients who did not receive immunotherapy after neoadjuvant therapy and underwent 3-6 cycles of therapy exhibited a poorer prognosis compared to those who received 1-2 cycles (HR, 2.731; 95%CI = 1.187-6.284; P = 0.018).

Conclusions

In conclusion, this study found that immunotherapy did not play a decisive role in neoadjuvant EC therapy. Instead, 1-2 cycles of chemotherapy or chemoradiotherapy were associated with a more favorable prognosis for these patients.
A bibliometric analysis of the advance of artificial intelligence in medicine
Authors: Lin Mian , Lin Lingzhi , Lin Lingling , Lin Zhengqiu , Yan Xiaoxiao
Published: February 2025

Introduction

The integration of artificial intelligence (AI) into medicine has ushered an era of unprecedented innovation, with substantial impacts on healthcare delivery and patient outcomes. Understanding the current development, primary research focuses, and key contributors in AI applications in medicine through bibliometric analysis is essential.

Methods

For this research, we utilized the Web of Science Core Collection as our main database and performed a review of literature covering the period from January 2019 to December 2023. VOSviewer and R-bibliometrix were performed to conduct bibliometric analysis and network visualization, including the number of publications, countries, journals, citations, authors, and keywords.

Results

A total of 1,811 publications on research for AI in medicine were released across 565 journals by 12,376 authors affiliated with 3,583 institutions from 97 countries. The United States became the foremost producer of scholarly works, significantly impacting the field. Harvard Medical School exhibited the highest publication count among all institutions. The Journal of Medical Internet Research achieved the highest H-index (19), publication count (76), and total citations (1,495). Four keyword clusters were identified, covering AI applications in digital health, COVID-19 and ChatGPT, precision medicine, and public health epidemiology. “Outcomes” and “Risk” demonstrated a notable upward trend, indicating the utilization of AI in engaging with clinicians and patients to discuss patients’ health condition risks, foreshadowing future research focal points.

Conclusion

Analyzing our bibliometric data allowed us to identify progress, focus areas, and emerging fields in AI for medicine, pointing to potential future research directions. Since 2019, there has been a steady rise in publications related to AI in medicine, indicating its rapid growth. In addition, we reviewed journals and significant publications to pinpoint prominent countries, institutions, and academics. Researchers will gain important insights into the current landscape, collaborative frameworks, and key research topics in the field from this study. The findings suggest directions for future research.
Detection of hemodynamic changes in a porcine lipopolysaccharide model of systemic inflammation using dynamic light scattering measurements of the microcirculation
Authors: te Nijenhuis Louwrina H. , Gangaram-Panday Norani H. , Specht Patricia A. C. , Fine Ilya , Elstein Nimrod , Mik Egbert G. , Harms Floor A. , Reiss Irwin K. M. , van Weteringen Willem
Published: February 2025

Background

The microcirculation is affected during sepsis, yet there is currently no clinically available technology for sepsis detection in the microcirculation. This study aimed to detect microcirculatory changes using a dynamic light scattering (DLS) skin sensor during an endotoxic shock with a systemic inflammatory response in a porcine lipopolysaccharide (LPS) model.

Methods

Thirty female Yorkshire x Norwegian Landrace pigs were divided into three groups: control, LPS, and LPS with resuscitation. After baseline measurements, LPS (1.75 μg∙kg−1∙h−1) was administered in progressively increasing dosages in the LPS and resuscitation groups. Two mDLS™ sensors, placed centrally and peripherally, measured total blood flow (TBF), relative blood velocity (RBV), and relative hemodynamic indices (relHIs) 1 h before (T0) and 1, 2, and 3 h after LPS administration (T1, T2, and T3). New DLS parameters describing heart rate variability (high-and low-frequency components HF and LF) and self-similarity (the Hurst exponent) were calculated.

Results

No differences in TBF, RBV, and HF values were seen between the study groups after LPS administration. LF was peripherally higher at T2 in subjects receiving LPS than in controls. RelHIs showed a change in blood distribution between T0 and T1 in the resuscitation group. Both intervention groups showed a Hurst exponent decrease centrally at T2 and peripherally already at T1.

Conclusion

Changes in microcirculatory parameters, relHIs, and the Hurst exponent, were recorded for 3 h following LPS administration. The Hurst exponent was significantly lower in the LPS and LPS with resuscitation groups than in controls. Further clinical studies are required to determine the sensitivity and specificity of the non-invasive mDLS™ sensor for sepsis detection.
Multiscale fusion enhanced spiking neural network for invasive BCI neural signal decoding
Authors: Song Yu , Han Liyuan , Zhang Tielin , Xu Bo
Published: February 2025

Brain-computer interfaces (BCIs) are an advanced fusion of neuroscience and artificial intelligence, requiring stable and long-term decoding of neural signals. Spiking Neural Networks (SNNs), with their neuronal dynamics and spike-based signal processing, are inherently well-suited for this task. This paper presents a novel approach utilizing a Multiscale Fusion enhanced Spiking Neural Network (MFSNN). The MFSNN emulates the parallel processing and multiscale feature fusion seen in human visual perception to enable real-time, efficient, and energy-conserving neural signal decoding. Initially, the MFSNN employs temporal convolutional networks and channel attention mechanisms to extract spatiotemporal features from raw data. It then enhances decoding performance by integrating these features through skip connections. Additionally, the MFSNN improves generalizability and robustness in cross-day signal decoding through mini-batch supervised generalization learning. In two benchmark invasive BCI paradigms, including the single-hand grasp-and-touch and center-and-out reach tasks, the MFSNN surpasses traditional artificial neural network methods, such as MLP and GRU, in both accuracy and computational efficiency. Moreover, the MFSNN's multiscale feature fusion framework is well-suited for the implementation on neuromorphic chips, offering an energy-efficient solution for online decoding of invasive BCI signals.
Analysis of the efficacy and safety of camrelizumab combined with chemotherapy for cervical cancer treatment
Authors: Yang Song-Tian , Yang Shuang , Wang Ji , Mu Xiao-Ling , Yan Bo
Published: February 2025

Introduction

In this study, we explored the effectiveness and safety of the immune checkpoint inhibitor camrelizumab in combination with chemotherapy for the treatment of cervical cancer by investigating adverse effects and changes in tumor volume, tumor activity, and biochemical indices.

Methods

In this retrospective analysis, the experimental group was administered intravenous camrelizumab in conjunction with a TP regimen (consisting of a paclitaxel analog and a platinum analog), while the control group was given only the TP regimen. The effectiveness of solid tumors, SCC-Ag values, tumor volume, and apparent diffusion coefficient (ADC) values, as well as adverse responses, were compared between the two groups.

Results

In the experimental group, 11 cases (22.45%) exhibited complete remission (CR), 27 cases (55.10%) demonstrated partial resolution (PR), and 11 cases (22.45%) showed stable disease (SD). The objective remission rate (ORR) was 77.55%, and the disease control rate (DCR) was 100%. In the control group, 10 cases (25.64%) exhibited CR, 18 cases (46.15%) demonstrated PR, 9 cases (23.08%) exhibited SD, and 2 cases (5.13%) exhibited disease progression. The ORR was 71.79%, and the DCR was 94.87%. A significant difference was observed between the two groups regarding the post-treatment SCC-Ag value, pre-treatment minimum ADC (minADC), and the change in size of minADC before and after treatment (P < 0.05). A comparison of the pre- and post-treatment size changes in tumor volume in patients with stage IIA2 cancer revealed significant differences (p < 0.05). No adverse responses of grade 3 or higher were detected.

Discussion

Our analysis showed that the combination of camrelizumab and chemotherapy effectively reduced tumor size and malignancy in cervical cancer treatment, demonstrating robust anti-tumor activity with a favorable safety profile.
Use of CatBoost algorithm to identify the need for surgery in infants with necrotizing enterocolitis
Authors: Jin Xinyun , Sun Wenqiang , Li Yihui , Su Yinglin , Xu Lingqi , Zhu Xueping
Published: February 2025

Background

Early identification of infants with necrotizing enterocolitis (NEC) at risk of surgery is essential for an effective treatment. This study aims to clarify the risk factors of surgical NEC and establish a prediction model by machine learning algorithm.

Methods

Infants with NEC were split into two groups based on whether they had surgery or not. Clinical data was collected and compared between the groups. Variables were analyzed with one-way logistic regression and predictive models were built using logistic regression and CatBoost algorithm. The models were evaluated and compared using Receiver Operating Characteristic (ROC) curves and feature importance. Feature importance was ranked using the SHapley Additive exPlanation method and model optimization was performed using feature culling. Final model was selected and a user-friendly GUI software was created for clinical use.

Results

The Catboost model performed better than the logistic regression model in terms of discriminative power. An interpretable final model with 14 features was built after the features were reduced according to the feature importance level. The final model accurately identified Surgicel NEC in the internal validation (AUC = 0.905) and was translated into a convenient tool to facilitate its use in clinical settings.

Conclusions

Catboost machine learning model related to infants with surgical NEC was successfully developed. A GUI interface was developed to assist clinicians in accurately identifying children who would benefit from surgery.
Early caffeine therapy decreases bronchopulmonary dysplasia but might increase mortality in preterm infants? a systematic review and meta-analysis
Authors: Ma Juan , Chen Long , Mu Kaihong , Tang Shifang , Shi Yuan
Published: February 2025

Objectives

To assess the effectiveness of early vs. late caffeine therapy for bronchopulmonary dysplasia (BPD) in infants.

Methods

PubMed, Embase, Web of Science, and Cochrane databases were searched up to October 2024. Studies comparing early and late caffeine therapy for BPD in infants were included. The primary outcomes were the incidence of BPD, severe BPD, and mortality.

Results

Eleven studies (1 RCT and 10 cohorts) with 64,749 patients (34,175 early and 30,574 late) were included. Meta-analysis revealed a significantly lower incidence of BPD (OR: 0.67; 95% CI: 0.56, 0.79; P < 0.00001) but higher mortality (OR: 1.20; 95% CI: 1.12, 1.29; P < 0.00001) in the early group. Subgroup analysis showed a significant difference in BPD incidence in retrospective studies (OR: 0.57; 95% CI: 0.44, 0.74; P < 0.0001), but not in prospective studies (OR: 0.84; 95% CI: 0.44, 1.61; P = 0.61). No significant difference was observed in severe BPD incidence (OR: 0.89; 95% CI: 0.34, 2.35; P = 0.81).

Conclusions

Early caffeine therapy may reduce BPD incidence but increase mortality risk in infants. More large-scale, prospective studies are needed to further evaluate the efficacy of early vs. late caffeine therapy for BPD.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=474351, PROSPERO (CRD42023474351).
Astragalus-containing Chinese herbal medicine used with Western medicine for lupus nephritis: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Jinjiao , Wu Mengyun , Liu Weiwei
Published: February 2025

Background

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that requires effective management to prevent kidney damage and other systemic effects. While Western medicine provides the standard treatment, incorporating traditional Chinese medicine, such as Astragalus-containing Chinese herbal medicine (CHM), may offer additional benefits in improving patient outcomes.

Objective

This study aims to conduct a systematic review and meta-analysis of the efficacy and safety of Astragalus in conjunction with Western medicine for the treatment of LN.

Methods

We conducted a comprehensive, global systematic search across databases including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang. Data were synthesized using fixed- or random-effects models, depending on the level of heterogeneity. Results were presented as standardized mean difference (SMD), risk ratios (RRs), or number needed to treat (NNT) with 95% confidence intervals (CIs). The Cochrane Q test and I2 statistics were used to test the heterogeneity assessment. Trial sequential analysis (TSA) was employed to assess the power of the results. All statistical analysis was carried out using STATA (version 16.0).

Result

The analysis included 14 RCTs, with a total of 800 patients (417 in the treatment group and 383 in the control group). Our meta-analysis revealed that patients treated with Astragalus-containing CHM alongside Western medicine showed markedly improved outcomes compared to those receiving only Western medicine. Significant improvements were observed in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (SMD = 1.01, 95% CI: 0.71–1.30, P < 0.001), 24-h proteinuria (SMD = 0.51, 95% CI: 0.35–0.66, P < 0.001SMD = 0.51, 95% CI: 0.35–0.66, P < 0.001), serum creatinine (SCr) levels (SMD = 0.64, 95%CI: 0.27–1.01, P < 0.001), blood urea nitrogen (BUN) levels (SMD = 0.73, 95%CI: 0.53–0.92, P < 0.001), and overall response rates (ORR) (RR = 1.21, 95%CI: 1.10–1.34, P < 0.001). Additionally, the incidence of adverse events (AEs), such as diarrhea, fever, and other symptoms, was significantly lower in the group treated with Astragalus-containing CHM and Western medicine (RR = 0.56, 95%CI: 0.42–0.73, P < 0.001). The TSA indicated that the data were sufficiently robust to draw reliable numerical conclusions regarding the ORR and the incidence of AEs.

Conclusion

The inclusion of Astragalus-containing CHM alongside Western medicine may be a promising strategy for to improve the therapeutic effectiveness and reduce toxicity in the treatment of LN.
Elucidation of Callistemon lanceolatus-derived natural compounds in STAT 3 pathway against human cancer cells: in silico and in vitro studies
Authors: Zafar Mubashir , Anwar Sadaf , Hussain Malik Asif , Iqbal Naveed , Ali Abrar , Sadaf  , Najm Mohammad Zeeshan , Kausar Mohd Adnan
Published: February 2025

Introduction

Many human tumours have hyperactive signal transducer and activator of transcription 3 (STAT3, positioning it as a prime target for natural compounds with anticancer properties. This study investigated three small-molecule STAT3 inhibitors derived from Callistemon lanceolatus: cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2″-o-galloyl)-β-d-galactopyranoside.

Material and methods

The compounds were explored through virtual screening and molecular dynamics (MD) simulations to understand the intracellular processing of activated STAT3. The biological effects of these STAT3 inhibitors on human cancer cells were assessed via simulation. Further, in-vitro studies were performed to exhibit the anti-cancer role of compounds on cancer cell lines.

Results and discussion

It is revealed through results that active components in these compounds inhibited cancer cell migration and invasion and suppressed the proliferation of noncancer cells. Moreover, these natural compounds from C. lanceolatus downregulated the expression of STAT3 downstream target proteins, indicating their potential as therapeutic agents against cancer. Thus, cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2″-o-galloyl)-β-d-galactopyranoside from C. lanceolatus are promising candidates for cancer treatment.
Ehretia genus: a comprehensive review of its botany, ethnomedicinal values, phytochemistry, pharmacology, toxicology and clinical studies
Authors: Jiang Sai , Wang Mengyun , Kaur Amanpreet , Jiang Lin , Cai Yuan , Luo Jiangyi , Li Minxi , Wang Hongxing , Wan Dan , Peng Yanmei
Published: February 2025

Background

The Ehretia genus, comprising 66 species in the Boraginaceae family, has a history of ethnomedicinal use for various ailments. This review focuses on the botany, traditional uses, phytochemistry, pharmacology, toxicology, clinical studies, cultivation, and commercial potential of the Ehretia genus, with the goal of enhancing current research and applications.

Methods

Literatures related to Ehretia species were compiled using keywords such as “Ehretia,” “traditional use,” “chemical constituents,” and “bioactivity” from scientific databases, including “China Knowledge Resource Integrated Databases (CNKI),” “Flora of China,” “Google Scholar,” “Hunan Library,” “Plants of the World Online,” and “Web of Science” and so on.

Results

From 1980 to August 2024, only 101 compounds have been identified within this genus, primarily consisting of flavonoids, phenylpropanoids, phenolics, benzoquinones, triterpenoids, and fatty acids, with phenylpropanoids being the main components. Extracts and compounds from Ehretia species exhibited various bioactivities, including antioxidant, hepatoprotective, analgesic, anti-inflammatory, antibacterial, and anticancer effects, etc.

Conclusion

Research on the Ehretia genus is limited, with many species remaining underexamined in terms of phytochemistry and pharmacology. Few active compounds have been isolated and assessed for biological activities, and there is a lack of investigation into their mechanisms of action. Despite its documented uses, Ehretia species remains less explored scientifically than other Boraginaceae genera, presenting significant research opportunities. Further comprehensive studies are necessary to deepen our understanding of this diverse genus and validate its therapeutic potential.
MFAP4 is a novel prognostic biomarker in glioma correlating with immunotherapy resistance and ferroptosis
Authors: Lv Yuanhao , Gao Ying , Di Wenyu , Li Zhaoyi , Shi Yashen , Hou Tianyuan , Chen Yiyang , Tian Jiaqi , Xu Miaoming , Su Wei , Zhang Min , Zhong Jiateng
Published: February 2025

Background

Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy.

Methods

Genes associated with immunotherapy resistance were identified by analyzing The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO) database. In addition, gene set enrichment analysis (GSEA) was utilized to reveal relevant signaling pathways. Co-expression, differential expression and functional analyses were performed using TCGA-GBM/LGG, TIMER 2.0, MetScape, GTEx and LinkedOmics databases. Relationships with immune infiltration, ferroptosis and immune checkpoint genes were assessed. Gene mutations were explored by cBioPortal. Logistic regression, Lasso analysis, Receiver Operating Characteristic (ROC), Kaplan-Meier analysis, and Nomogram modeling assessed the correlation between MFAP4 and clinicopathological features of gliomas. By analyzing different datasets, we found that MFAP4 was aberrantly overexpressed in gliomas and correlated with poor clinicopathological features of gliomas. MFAP4 was an independent prognostic indicator and significantly correlated with glioma progression. We also performed functional and pathway enrichment analyses of MFAP4 in gliomas to explore its biological functions and potential molecular mechanisms in gliomas.

Results

MFAP4 was significantly elevated in glioma tissues compared to controls. MFAP4-related genes showed differential expression in pathways involving cytokines. Significant associations between MFAP4 levels, immune infiltration, ferroptosis, and immune checkpoint genes were found in glioma tissues. MFAP4 levels were correlated with glioma stage, histological type, and 1p/19q status, and independently predicted overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). MFAP4 expression is effective in distinguishing tumor tissue from normal brain tissue. Furthermore, Spearman Correlation emphasizes the significant relationship between MFAP4 and ferroptosis-related genes.

Conclusion

Our study demonstrated that MFAP4 is aberrantly overexpressed in gliomas and correlates with adverse clinicopathological features. MFAP4 has relevance in regulating both tumor immunity and iron death, and cellular function assays have demonstrated that MFAP4 promotes the proliferation, migration, and invasion of glioma cells.
Inverse association between atherogenic index of plasma and testosterone in US adult males: A large cross-sectional study from the NAHNES 2011–2016
Authors: Li Tanjian , Chen Lulu , Liang Xin , Li Xinya , Li Yaqin , Huang Yuting , Wang Yu
Published: February 2025

Background and objectives

The atherogenic index of plasma (AIP), defined as log10 (triglycerides/high-density lipoprotein cholesterol), serves as a biomarker for atherosclerosis and cardiovascular disease (CVD). It is also associated with conditions such as type 2 diabetes, insulin resistance, depression, and both cardiovascular and overall mortality. Serum lipids have been proven to influence serum testosterone levels, and AIP is a significant marker of lipid levels. We hypothesize that AIP may have a specific relationship with testosterone. This article aims to evaluate the correlation between AIP and total testosterone (TT), as well as testosterone deficiency (TD), among the U.S. population.

Methods

Data were collected from the National Health and Nutrition Examination Survey (NHANES) database between 2011 and 2016. This study was categorized into four groups based on the quartiles of AIP. Weighted multivariate linear regression and logistic regression were utilized to evaluate the relationships between AIP and TT, TD. Restricted cubic spline (RCS) was used to investigate the non-linear association between AIP and TT and TD. The subgroup analysis method was employed to investigate the relationships between AIP and TT, TD across various stratifications. Ultimately, the sensitivity study involved a comparison of weighted and unweighted data analyses to ascertain the stability of the conclusions.

Results

A total of 2,572 participants were included in the final study. After adjusting for all confounding factors, multivariate linear regression showed that AIP was independently negatively associated with TT (β = −93.42, 95%CI: −123.66, −63.18, P < 0.001), and multivariate logistic regression showed that AIP level was associated with higher risk of TD (OR = 3.45, 95%CI: 2.09, 5.69, P < 0.001). In the quartile of AIP, TT levels decreased the most (β = −74.81, 95%CI: −105.27, −44.35, p < 0.001) and the risk of TD was highest (OR = 2.89, 95%CI: 1.70, 4.93, p < 0.001). In addition, stratified analyses showed similar results in all subgroups except those with diabetes (P for interaction >0.05 for all comparisons). The final sensitivity analysis revealed that elevated AIP were also associated with decreased TT (β = −101.74, 95%CI: −123.18, −80.3, P < 0.001) and increased incidence of TD (OR = 3.01, 95%CI: 2.17, 4.17, P < 0.001) on unweighted data.

Conclusion

Increased levels of AIP correlate with decreased TT levels and a higher prevalence of TD. Additional research is necessary to investigate the underlying mechanisms connecting them.
Heterogeneity of ventricular action potentials in neonatal rat cardiomyocytes and methodological aspects of patch clamp measurements
Authors: Syren Pascal , Zlatopolskaia Anna , Bruehl Claus , Schöffel Axel , Caspari Teresa , Heß Chiara , Frey Norbert , Thomas Dierk , Lugenbiel Patrick
Published: February 2025

Measurement of the ventricular action potential (AP) via whole-cell patch clamp is an important contributor to cardiac electrophysiological research. Neonatal rat ventricular cardiomyocytes (NRVCM) are a commonly used model, in particular for stressor- or drug-related questions. High variability of APs and individual methodological settings hinder comparison both in individual studies and, to an even greater degree, between different projects. This study aims to describe sources of AP heterogeneity in NRVCM related to patch clamp measurement with a focus on resolvable causes. Therefore, AP of NRVCM were induced in whole-cell configuration and measured in current-clamp mode. The effects of varying setup temperature, electrode resistance, resting- (RMP), respectively holding membrane potential (HMP), induction approach, current pulse duration and amplitude plus total assay duration were studied and compared to systematically analyzed literature. We analyzed the impact on different output parameters, namely, maximal upstroke velocity (dV/dt), maximal AP amplitude (APA) and AP duration at different percentages (XX%) of repolarization, APDXX. In a comparative literature research, we found that mean APD90 in between 27.0 and 560.7 ms (own data 59.7 ± 5.8 ms) were described, with high variability and likely non-Gaussian distribution. In this study, APD90, APD50 and APD30, are decreased at more negative RMP (respectively HMP) values. E.g., APD90 is shortened by ∼60% after lowering HMP from −70 mV to −90 mV) while dV/dt and APA are increased at a more negative HMP. Pulse duration in induction did not affect main AP parameters itself, but induction energy levels above 1.5-fold the threshold energy level increased APA, while APD50 and APD90 were shortened. During series of APs at 1 Hz, spike duration (APD90) decreased by ∼27%, with stable AP after the third repetitive AP. Spike duration did also decreased by ∼40% after prolongated measurements for 21 min, indicating degradation of electrophysiological properties. To improve data quality in NRVCM-APs, we suggest using a constant HMP, adjustment of current pulse amplitude to the individual cells’ threshold and the use of repetitive AP-inductions. Finally, we suggest the use of nonparametric statistical methods for statistical analysis. These aspects could reduce variability and lead to more reliable and comparable data.
Genome-wide identification and expression profile analysis of TALE superfamily genes under hormone and abiotic stress in maize (Zea may L.)
Authors: Guan Peiyan , Zhao Dongbo , Wei Longxue , Cui Peipei , Zhang Shicai
Published: February 2025

Introduction

The three-amino-acid-loop-extension (TALE) of the homeobox superfamily genes plays important roles in plant growth, development, and responses to environmental stress. Although TALE members have been identified in various species, they have not been systematically characterized in maize and their expression profiles under ABA hormone and abiotic stress are unknown.

Methods

Bioinformatics methods were employed to identify the TALE family genes in the maize genome. The expression levels of ZmTALEs under ABA, salt, drought, and high temperature conditions was detected by qRT-PCR. The subcellular localization of ZmKNOX05 and ZmBELL11 proteins was observed in maize protoplasts.

Results

In this study, we identified 52 TALE members in maize, which can be divided into two subfamilies, KNOX and BELL. ZmKNOXs and ZmBELLs can be further divided into two subclasses based on the domains they contain. The protein characterizations and gene structures in the same subclass were similar, whereas they were distinct across different subclasses. There were 18 collinear gene pairs in maize genome. Inter-species evolutionary analyses showed that TALE family genes of maize were more homologous to monocotyledons than to dicotyledons. The promoter regions of ZmTALE contained abundant stress-responsive, hormone-responsive, light-responsive, and plant growth and development cis-elements. Specific spatiotemporal expression patterns analysis showed that ZmBELLs were highly expressed in root and mature leaf, whereas the ZmKNOX1 subfamily genes were more expressed in the primordium, internode, vegetative meristem, and root during developmental stages. It was found that most ZmTALEs could respond to ABA, drought, high temperature, and salt stress, indicating their roles in hormone and abiotic stress responsive. ZmKNOX05 and ZmBELL11 were cloned from B73 maize. Unexpectedly, a novel alternative transcript with a 99-base deletion for ZmKNOX05 were found, named ZmKNOX05.2, which exhibited alternative splicing event at the noncanonical site. Subcellular localization analysis revealed that ZmKNOX05.1-eGFP and ZmKNOX05.2-eGFP were localized in both the nucleus and cytoplasm, while ZmBELL11-eGFP was localized in perinuclear cytoplasm (perinuclear region of the cytoplasm).

Discussion

We identified TALE superfamily members in maize and conducted a comprehensive and systematic analysis. These results can lay the foundation for analysis of the functions of ZmTALE genes under ABA and abiotic stresses.