bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable biosurfactant production from secondary feedstock—recent advances, process optimization and perspectives
Authors: Miao Yahui , To Ming Ho , Siddiqui Muhammad Ahmar , Wang Huaimin , Lodens Sofie , Chopra Shauhrat S. , Kaur Guneet , Roelants Sophie L. K. W. , Lin Carol Sze Ki
Published: January 2024

Biosurfactants have garnered increased attention lately due to their superiority of their properties over fossil-derived counterparts. While the cost of production remains a significant hurdle to surpass synthetic surfactants, biosurfactants have been anticipated to gain a larger market share in the coming decades. Among these, glycolipids, a type of low-molecular-weight biosurfactant, stand out for their efficacy in reducing surface and interfacial tension, which made them highly sought-after for various surfactant-related applications. Glycolipids are composed of hydrophilic carbohydrate moieties linked to hydrophobic fatty acid chains through ester bonds that mainly include rhamnolipids, trehalose lipids, sophorolipids, and mannosylerythritol lipids. This review highlights the current landscape of glycolipids and covers specific glycolipid productivity and the diverse range of products found in the global market. Applications such as bioremediation, food processing, petroleum refining, biomedical uses, and increasing agriculture output have been discussed. Additionally, the latest advancements in production cost reduction for glycolipid and the challenges of utilizing second-generation feedstocks for sustainable production are also thoroughly examined. Overall, this review proposes a balance between environmental advantages, economic viability, and societal benefits through the optimized integration of secondary feedstocks in biosurfactant production.
Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis
Authors: Dai Xiaoting , Zhou Litian , He Xiaopu , Hua Jie , Chen Liang , Lu Yingying
Published: January 2024

Background

Apoptosis is associated with the pathogenesis of Mycobacterium tuberculosis infection. This study aims to identify apoptosis-related genes as biomarkers for differentiating active tuberculosis (ATB) from latent tuberculosis infection (LTBI).

Methods

The tuberculosis (TB) datasets (GSE19491, GSE62525, and GSE28623) were downloaded from the Gene Expression Omnibus (GEO) database. The diagnostic biomarkers differentiating ATB from LTBI were identified by combining the data of protein-protein interaction network, differentially expressed gene, Weighted Gene Co-Expression Network Analysis (WGCNA), and receiver operating characteristic (ROC) analyses. Machine learning algorithms were employed to validate the diagnostic ability of the biomarkers. Enrichment analysis for biomarkers was established, and potential drugs were predicted. The association between biomarkers and N6-methyladenosine (m6A) or 5-methylated cytosine (m5C) regulators was evaluated.

Results

Six biomarkers including CASP1, TNFSF10, CASP4, CASP5, IFI16, and ATF3 were obtained for differentiating ATB from LTBI. They showed strong diagnostic performances, with area under ROC (AUC) values > 0.7. Enrichment analysis demonstrated that the biomarkers were involved in immune and inflammation responses. Furthermore, 24 drugs, including progesterone and emricasan, were predicted. The correlation analysis revealed that biomarkers were positively correlated with most m6A or m5C regulators.

Conclusion

The six ARGs can serve as effective biomarkers differentiating ATB from LTBI and provide insight into the pathogenesis of Mycobacterium tuberculosis infection.
Strategies for combating antibiotic resistance in bacterial biofilms
Authors: Grooters Kayla E. , Ku Jennifer C. , Richter David M. , Krinock Matthew J. , Minor Ashley , Li Patrick , Kim Audrey , Sawyer Robert , Li Yong
Published: January 2024

Biofilms, which are complexes of microorganisms that adhere to surfaces and secrete protective extracellular matrices, wield substantial influence across diverse domains such as medicine, industry, and environmental science. Despite ongoing challenges posed by biofilms in clinical medicine, research in this field remains dynamic and indeterminate. This article provides a contemporary assessment of biofilms and their treatment, with a focus on recent advances, to chronicle the evolving landscape of biofilm research.
Features of trastuzumab-related cardiac dysfunction: deformation analysis outside left ventricular global longitudinal strain
Authors: Nhat Giang M. , Hai Nguyen H. , Duc Vo T. , Tri Ho H. Q. , Hoa Chau N.
Published: January 2024

Background

Cancer therapy-related cardiac dysfunction due to trastuzumab has been well-known for many years, and echocardiographic surveillance is recommended every 3 months in patients undergoing trastuzumab treatment, irrespective of the baseline cardiotoxicity risk. However, the potential harm and cost of overscreening in low- and moderate-risk patients have become great concerns.

Objectives

This study aimed to identify the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the behaviours of left and right heart deformations during trastuzumab chemotherapy in low- and moderate-risk patients.

Methods

We prospectively enrolled 110 anthracycline-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive trastuzumab. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycle and 3 weeks after the final dose of trastuzumab. The baseline risk of CTRCD was graded according to the risk score proposed by the Heart Failure Association (HFA) Cardio-Oncology Working Group and the International Cardio-Oncology Society (ICOS). CTRCD and its severity were defined according to the current European Society of Cardiology (ESC) guidelines.

Results

Twelve (10.9%) patients had asymptomatic CTRCD. All CTRCD occurred sporadically during the first 9 months of the active trastuzumab regimen in both low- and moderate-risk patients. While CTRCD was graded as moderate severity in 41.7% of patients and heart failure therapy was initiated promptly, no irreversible cardiotoxicity or trastuzumab interruption was recorded at the end of follow-up. Among the left and right heart deformation indices, only LV-GLS decreased significantly in the CTRCD group during the trastuzumab regimen.

Conclusions

CTRCD is prevalent in patients with non-high-risk breast cancer undergoing trastuzumab chemotherapy. Low- and moderate-risk patients show distinct responses to trastuzumab. The LV-GLS is the only deformation index sensitive to early trastuzumab-related cardiac dysfunction.
Evaluating the performance of WRF in simulating winds and surface meteorology during a Southern California wildfire event
Authors: Kumar Mukesh , Kosović Branko , Nayak Hara P. , Porter William C. , Randerson James T. , Banerjee Tirtha
Published: January 2024

The intensity and frequency of wildfires in California (CA) have increased in recent years, causing significant damage to human health and property. In October 2007, a number of small fire events, collectively referred to as the Witch Creek Fire or Witch Fire started in Southern CA and intensified under strong Santa Ana winds. As a test of current mesoscale modeling capabilities, we use the Weather Research and Forecasting (WRF) model to simulate the 2007 wildfire event in terms of meteorological conditions. The main objectives of the present study are to investigate the impact of horizontal grid resolution and planetary boundary layer (PBL) scheme on the model simulation of meteorological conditions associated with a Mega fire. We evaluate the predictive capability of the WRF model to simulate key meteorological and fire-weather forecast parameters such as wind, moisture, and temperature. Results of this study suggest that more accurate predictions of temperature and wind speed relevant for better prediction of wildfire spread can be achieved by downscaling regional numerical weather prediction products to 1 km resolution. Furthermore, accurate prediction of near-surface conditions depends on the choice of the planetary boundary layer parameterization. The MYNN parameterization yields more accurate prediction as compared to the YSU parameterization. WRF simulations at 1 km resolution result in better predictions of temperature and wind speed than relative humidity during the 2007 Witch Fire. In summary, the MYNN PBL parameterization scheme with finer grid resolution simulations improves the prediction of near-surface meteorological conditions during a wildfire event.
Development and initial validation of a creative self-efficacy scale for undergraduates: categorical confirmatory factor analysis and multidimensional item response theory
Authors: Abulela Mohammed A. A.
Published: January 2024

Creative self-efficacy (CSE) has recently received much attention due to its association with student learning and creativity. To that end, a CSE scale was developed for undergraduates and sources of validity evidence based on scale content, response processes, and internal structure were collected. Score reliability, using categorical omega based on the categorical confirmatory factor analysis model and marginal reliability for response pattern scores based on item response theory (IRT), were estimated. After various revision iterations of the initial 28-item pool by 10 subject matter experts and 18 undergraduates, some items were revised, four items were dropped, and ultimately 24 items were field tested for measuring two hypothesized dimensions of CSE among 602 undergraduates. Categorical confirmatory factor analysis results indicated that the two-dimensional model had better fit. Similarly, between the two competing multidimensional IRT models, the two-dimensional graded response model had the best fit. Categorical omega coefficients and marginal reliability for response pattern scores were, respectively, 0.88 and 0.81 for the two underlying dimensions.
Optimizing the construction of ecological networks in Beijing using a morphological spatial pattern analysis—minimal cumulative resistance model
Authors: Na Yueqi , Hong Zhujun , Ren Siyuan , Huang Kai
Published: January 2024

Introduction: With the increasing fragmentation of landscapes caused by rapid urbanisation, constructing ecological networks strengthen the connectivity between fragmented habitat patches. As the capital of China, Beijing has a rapid development, resulting in a serious landscape fragmentation, and needing an urgent demand for this study to improve the ecological network system.

Methods: In this study, we choose the elevation, slope, Normalized Difference Vegetation Index and land use data of Beijing in 2020 as the data use. Morphological spatial pattern analysis (MSPA) was used to identify ecological source areas for Beijing, Minimal cumulative resistance (MCR) and gravity models were used to construct ecological network, and stepping stones to improve it.

Results: The core area of Beijing had the highest proportion (96.17%) of all landscape types, forest accounting for 82.01% thereof. Ten core areas were identified as ecological source areas. Forty-five ecological corridors (8 major and 37 ordinary) were constructed. The ecological corridors are mainly concentrated in the middle and eastern regions where ecological mobility is limited. Constructing stepping stones would help uphold the region’s ecological service functions and ecosystem balance. Twenty-nine stepping stones and 32 ecological obstacles were used to create the optimised ecological network, consisting of 171.

Discussion: The results provide an optimised ecological model for Beijing and a reference constructing ecological spatial networks for the sustainable development of ecological environments in high-density urban areas.
Water resource security evaluation and barrier analysis in Henan Province utilizing the DPSIR framework
Authors: Zhao Mengdie , Wei Jinhai , Han Yuping , Shi Jiahao , Wang Shuaibin
Published: January 2024

Water resource health is one of the necessary conditions for society to achieve sustainable development. Due to the predominant focus of most studies on relatively short time spans, with limited attention to long time series and spatial trends, this study, using various regions of Henan Province as a case study, constructs a water resource security assessment framework based on the DPSIR model encompassing Drivers (D), Pressures (P), State (S), Impact (I), and Response (R) dimensions, with a selection of 19 evaluation indicators. Based on this evaluation index system, the CRITIC-TOPSIS evaluation method is formulated by integrating the CRITIC (Criteria Importance Through Intercriteria Correlation) and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) models. This method is employed to assess the degree of water resource security in Henan Province from 2013 to 2022. And the Obstruction Degree Model is introduced to diagnose the water resource security levels in various regions of Henan Province. The assessment results indicate that over the past decade, the overall level of water resource security in various regions of Henan Province has shown an increasing trend. Irrigated area, per capita water resources, water consumption per unit of industrial value added, per acre water consumption for agricultural irrigation, the ratio of river length meeting water quality standards, groundwater supply proportion, and sewage treatment rate are identified as the primary obstacles influencing the water resource security levels in different regions of Henan Province. The research outcomes of this study can serve as theoretical foundations to enhance urban water resource security globally, ultimately facilitating sustainable development.
Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa
Authors: Carter Chris , Boggs Tracy , Case Laura E. , Kishnani Priya
Published: January 2024

Introduction: Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues. There have been trials comparing the efficacy of alglucosidase and avalglucosidase, but there remains a need for more real-world data on patients who switched from alglucosidase to avalglucosidase.

Methods: A chart review was conducted on n = 15 patients with late-onset Pompe disease followed at a single center who switched from alglucosidase to avalglucosidase and continued for at least 6 months.

Results: A total of n = 8/15 patients received alglucosidase for more than 3 years prior to switching, and n = 7/15 received it for more than 5 years prior to switching. There were statistically significant improvements in CK, Hex4, and AST with mean differences of −104.8 U/L, −3.0 mmol/molCr, and −14.7 U/L, respectively, post-switch. 6-Minute Walk Test; comfortable gait speed; Gait, Stairs, Gower, Chair; and Quick Motor Function Test scores improved or stabilized in most patients post-switch (n = 8/12, n = 11/12, n = 9/12, n =7/11, respectively). Of n = 7 patients with pulmonary function testing, n = 4/7 had improved upright FVC. Patient-reported outcomes revealed improvements in dyspnea (n = 4/4), physical function (n = 3/4), fatigue (n = 2/3), and lower back pain (n = 3/3). Avalglucosidase was well tolerated without infusion-associated reactions, and all n = 7 patients on home infusions continued receiving ERT at home. Anti-drug antibodies were seen in n = 9/10 of patients on alglucosidase and n = 8/13 of those on avalglucosidase, with titers below 12,800 in a majority of patients. We also present the first outcome data for a patient with LOPD who is non-ambulatory and a full-time wheelchair user; she demonstrated meaningful improvements in quality of life and motor function with the switch.

Discussion: In summary, improved outcomes were seen in most patients, with a subset whose decline persisted. This study presents evidence that switching from alglucosidase to avalglucosidase may be associated with improved outcomes in certain patients with LOPD.
Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study
Authors: He Menghao , Xu Chun , Yang Renyi , Liu Lijuan , Zhou Desheng , Yan Siyang
Published: January 2024

Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.

Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted.

Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C17H18N2O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk.

Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.
Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity
Authors: Liang Yingnan , Chen Qi , Chang Yue , Han Junsong , Yan Jiaxin , Chen Zhenjie , Zhou Jingwei
Published: January 2024

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.
The uncharted territory of host-pathogen interaction in tuberculosis
Authors: Ghoshal Antara , Verma Akanksha , Bhaskar Ashima , Dwivedi Ved Prakash
Published: January 2024

Mycobacterium tuberculosis (M.tb) effectively manipulates the host processes to establish the deadly respiratory disease, Tuberculosis (TB). M.tb has developed key mechanisms to disrupt the host cell health to combat immune responses and replicate efficaciously. M.tb antigens such as ESAT-6, 19kDa lipoprotein, Hip1, and Hsp70 destroy the integrity of cell organelles (Mitochondria, Endoplasmic Reticulum, Nucleus, Phagosomes) or delay innate/adaptive cell responses. This is followed by the induction of cellular stress responses in the host. Such cells can either undergo various cell death processes such as apoptosis or necrosis, or mount effective immune responses to clear the invading pathogen. Further, to combat the infection progression, the host secretes extracellular vesicles such as exosomes to initiate immune signaling. The exosomes can contain M.tb as well as host cell-derived peptides that can act as a double-edged sword in the immune signaling event. The host-symbiont microbiota produces various metabolites that are beneficial for maintaining healthy tissue microenvironment. In juxtaposition to the above-mentioned mechanisms, M.tb dysregulates the gut and respiratory microbiome to support its replication and dissemination process. The above-mentioned interconnected host cellular processes of Immunometabolism, Cellular stress, Host Microbiome, and Extracellular vesicles are less explored in the realm of exploration of novel Host-directed therapies for TB. Therefore, this review highlights the intertwined host cellular processes to control M.tb survival and showcases the important factors that can be targeted for designing efficacious therapy.
Comprehending the cuproptosis and cancer-immunity cycle network: delving into the immune landscape and its predictive role in breast cancer immunotherapy responses and clinical endpoints
Authors: Liu Xiangwei , Xu Feng , Zhao Kunkun , Liu Yunfei , Ye Guolin , Zhang Xin , Qu Yanyu
Published: January 2024

Background

The role of cuproptosis, a phenomenon associated with tumor metabolism and immunological identification, remains underexplored, particularly in relation to the cancer-immunity cycle (CIC) network. This study aims to rigorously examine the impact of the cuproptosis-CIC nexus on immune reactions and prognostic outcomes in patients with breast cancer (BC), striving to establish a comprehensive prognostic model.

Methods

In the study, we segregated data obtained from TCGA, GEO, and ICGC using CICs retrieved from the TIP database. We constructed a genetic prognostic framework using the LASSO-Cox model, followed by its validation through Cox proportional hazards regression. This framework’s validity was further confirmed with data from ICGC and GEO. Explorations of the tumor microenvironment were carried out through the application of ESTIMATE and CIBERSORT algorithms, as well as machine learning techniques, to identify potential treatment strategies. Single-cell sequencing methods were utilized to delineate the spatial distribution of key genes within the various cell types in the tumor milieu. To explore the critical role of the identified CICs, experiments were conducted focusing on cell survival and migration abilities.

Results

In our research, we identified a set of 4 crucial cuproptosis-CICs that have a profound impact on patient longevity and their response to immunotherapy. By leveraging these identified CICs, we constructed a predictive model that efficiently estimates patient prognoses. Detailed analyses at the single-cell level showed that the significance of CICs. Experimental approaches, including CCK-8, Transwell, and wound healing assays, revealed that the protein HSPA9 restricts the growth and movement of breast cancer cells. Furthermore, our studies using immunofluorescence techniques demonstrated that suppressing HSPA9 leads to a notable increase in ceramide levels.

Conclusion

This research outlines a network of cuproptosis-CICs and constructs a predictive nomogram. Our model holds great promise for healthcare professionals to personalize treatment approaches for individuals with breast cancer. The work provides insights into the complex relationship between the cuproptosis-CIC network and the cancer immune microenvironment, setting the stage for novel approaches to cancer immunotherapy. By focusing on the essential gene HSPA9 within the cancer-immunity cycle, this strategy has the potential to significantly improve the efficacy of treatments against breast cancer.
Effectiveness and cost of integrated cognitive and balance training for balance and falls in cerebellar ataxia: a blinded two-arm parallel group RCT
Authors: Winser Stanley J. , Chan Anne Y. Y. , Whitney Susan L. , Chen Cynthia H. , Pang Marco Y. C.
Published: January 2024

Background

In patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks.

Objective

Evaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA.

Methods

This RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4).

Results

Compared to single-task training CIBT improved the dual-task cost of physical task [MD −8.36 95% CI (−14.47 to −2.36, p < 0.01), dual-tasking ability [−6.93 (−13.16 to −0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [−2.03 (−4.04 to −0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [−18.53 (−25.81 to −11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [−1.11 (−1.42 to −0.78); p < 0.01] and right [−0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group.

Conclusion

We found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim.

Clinical trial registration

https://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501].
Deep learning-based multimodality classification of chronic mild traumatic brain injury using resting-state functional MRI and PET imaging
Authors: Vedaei Faezeh , Mashhadi Najmeh , Alizadeh Mahdi , Zabrecky George , Monti Daniel , Wintering Nancy , Navarreto Emily , Hriso Chloe , Newberg Andrew B. , Mohamed Feroze B.
Published: January 2024

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and improves classification performance. Additionally, a novel data interpretation approach was utilized to identify top-performing features learned by the AEs. Our method delivered a classification accuracy within the range of 79–91.67% for single neuroimaging modalities. However, the performance of classification improved to 95.83%, thereby employing the multimodality model. The models have identified several brain regions located in the default mode network, sensorimotor network, visual cortex, cerebellum, and limbic system as the most discriminative features. We suggest that this approach could be extended to the objective biomarkers predicting mTBI in clinical settings.
Case report: Acute pancreatitis in lung adenocarcinoma with small cell transformation after multiple line targeted therapy
Authors: Jing Yaoyao , Li Xiaoxiao , Sun Xiaoyuan , Ren Minghan , Xiao Ruoxi , Zhao Jiayu , Liu Zimin
Published: January 2024

In lung cancer, metastasis to the liver, bones, brain, and adrenal glands is more commonly observed, whereas pancreatic metastasis from lung cancer is relatively rare. We present a case of a patient with an 8-year history of lung adenocarcinoma (LUAD) who was admitted to our institution exhibiting symptoms consistent with acute pancreatitis. Subsequent histopathological examination through puncture confirmed the occurrence of pancreatic metastasis originating from small cell lung cancer (SCLC). During a multidisciplinary team discussion, we reached a consensus in diagnosing the patient with post-transformation small cell carcinoma alongside moderately severe pancreatitis, which was determined to be a consequence of pancreatic metastasis. The patient received a regimen of etoposide and cisplatin chemotherapy. This unique clinical case highlights the importance of further investigating the factors contributing to pancreatic metastasis in patients with lung cancer, as the underlying mechanisms remain unclear. Understanding these exceptional metastatic events is vital in devising effective therapeutic strategies and improving patient prognosis. Our findings emphasize the need for continued surveillance and comprehensive management of lung cancer patients, particularly those with resistant forms of the disease, to promptly identify and address the progression of metastatic events to uncommon sites such as the pancreas.
Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma
Authors: Wang Yumin , Fleishman Joshua S. , Li Tongda , Li Yulin , Ren Zhao , Chen Jichao , Ding Mingchao
Published: January 2024

In light of a global rise in the number of patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of hepatocellular carcinoma (HCC), with the annual occurrence of MASLD-driven HCC expected to increase by 45%–130% by 2030. Although MASLD has become a serious major public health threat globally, the exact molecular mechanisms mediating MASLD-driven HCC remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on the utility of bioactive compounds to halt the progression of MASLD to MASLD-driven HCC. In this review, we first briefly review the recent progress of the possible mechanisms of pathogenesis and progression for MASLD-driven HCC. We then discuss the application of bioactive compounds to mitigate MASLD-driven HCC through different modulatory mechanisms encompassing anti-inflammatory, lipid metabolic, and gut microbial pathways, providing valuable information for future treatment and prevention of MASLD-driven HCC. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of MASLD-driven HCC is still warranted.
Systematic review and meta-analysis of the interventional effects of resveratrol in a rat model of myocardial ischemia-reperfusion injury
Authors: Zhang Dong-Ze , Jia Ming-Yang , Wei Hong-Yu , Yao Ming , Jiang Li-Hong
Published: January 2024

Objective: To evaluate the intervention effect of resveratrol on rat model of myocardial ischemia-reperfusion injury.

Methods: The relevant studies on the intervention of resveratrol on rat models of myocardial ischemia reperfusion injury were searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and China Science and Technology Journal Database from the start of database establishment to January 2023. Data were extracted from studies that met the inclusion criteria. The results included electrocardiogram (ECG) and myocardial injury markers: ST changes, cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH); hemodynamic indicators: heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of increase of left ventricular pressure (+dp/dtmax), maximum rate of decrease of left ventricular pressure (−dp/dtmax); oxidative damage indicators: nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA); inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); apoptosis index: B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), cardiomyocyte apoptosis index (AI); heart tissue structure: myocardial infarction size. Finally, a meta-analysis of these results was conducted. The methodological quality of the studies was assessed using the SYRCLE Bias Risk tool.

Results: A total of 43 studies were included in the meta-analysis, and the quality of the included studies was assessed. It was found that the evidence quality of these 43 studies was low, and no study was judged to have low risk bias in all risk assessments. The results showed that resveratrol could reduce ST segment, cTn-I, cTn-T, CK, CK-MB, LDH, LVEDP, ROS, MDA, TNF-α, IL-6, AI levels and myocardial infarction size. HR, LVDP, LVSP, +dp/dtmax, NO, Bcl-2, and SOD levels were increased. However, resveratrol had no significant effect on -dp/dtmax and Bax outcome measures.

Conclusion: Resveratrol can reduce ST segment in rat model of myocardial ischemia-reperfusion injury, alleviate myocardial injury, improve ventricular systolic and diastolic ability in hemodynamics, reduce inflammatory response and oxidative damage, and reduce myocardial necrosis and apoptosis. Due to the low quality of the methodologies included in the studies, additional research is required.
Urinary biomarkers associated with podocyte injury in lupus nephritis
Authors: Guo Zhiying , Guo Qianyu , Li Xiaochen , Gao Xinnan , Zhang Liyun , Xu Ke
Published: January 2024

The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN.
Kidney derived apolipoprotein M and its role in acute kidney injury
Authors: Bisgaard Line S. , Christensen Pernille M. , Oh Jeongah , Torta Federico , Füchtbauer Ernst-Martin , Nielsen Lars Bo , Christoffersen Christina
Published: January 2024

Aim: Apolipoprotein M (apoM) is mainly expressed in liver and in proximal tubular epithelial cells in the kidney. In plasma, apoM associates with HDL particles via a retained signal peptide and carries sphingosine-1-phosphate (S1P), a small bioactive lipid. ApoM is undetectable in urine from healthy individuals but lack of megalin receptors in proximal tubuli cells induces loss of apoM into the urine. Besides this, very little is known about kidney-derived apoM. The aim of this study was to address the role of apoM in kidney biology and in acute kidney injury.

Methods: A novel kidney-specific human apoM transgenic mouse model (RPTEC-hapoMTG) was generated and subjected to either cisplatin or ischemia/reperfusion injury. Further, a stable transfection of HK-2 cells overexpressing human apoM (HK-2-hapoMTG) was developed to study the pattern of apoM secretion in proximal tubuli cells.

Results: Human apoM was present in plasma from RPTEC-hapoMTG mice (mean 0.18 μM), with a significant increase in plasma S1P levels. In vitro apoM was secreted to both the apical (urine) and basolateral (blood) compartment from proximal tubular epithelial cells. However, no differences in kidney injury score was seen between RPTEC-hapoMTG and wild type (WT) mice upon kidney injury. Further, gene expression of inflammatory markers (i.e., IL6, MCP-1) was similar upon ischemia/reperfusion injury.

Conclusion: Our study suggests that kidney-derived apoM is secreted to plasma, supporting a role for apoM in sequestering molecules from excretion in urine. However, overexpression of human apoM in the kidney did not protect against acute kidney injury.
To have value, comparisons of high-throughput phenotyping methods need statistical tests of bias and variance
Authors: McGrath Justin M. , Siebers Matthew H. , Fu Peng , Long Stephen P. , Bernacchi Carl J.
Published: January 2024

The gap between genomics and phenomics is narrowing. The rate at which it is narrowing, however, is being slowed by improper statistical comparison of methods. Quantification using Pearson’s correlation coefficient (r) is commonly used to assess method quality, but it is an often misleading statistic for this purpose as it is unable to provide information about the relative quality of two methods. Using r can both erroneously discount methods that are inherently more precise and validate methods that are less accurate. These errors occur because of logical flaws inherent in the use of r when comparing methods, not as a problem of limited sample size or the unavoidable possibility of a type I error. A popular alternative to using r is to measure the limits of agreement (LOA). However both r and LOA fail to identify which instrument is more or less variable than the other and can lead to incorrect conclusions about method quality. An alternative approach, comparing variances of methods, requires repeated measurements of the same subject, but avoids incorrect conclusions. Variance comparison is arguably the most important component of method validation and, thus, when repeated measurements are possible, variance comparison provides considerable value to these studies. Statistical tests to compare variances presented here are well established, easy to interpret and ubiquitously available. The widespread use of r has potentially led to numerous incorrect conclusions about method quality, hampering development, and the approach described here would be useful to advance high throughput phenotyping methods but can also extend into any branch of science. The adoption of the statistical techniques outlined in this paper will help speed the adoption of new high throughput phenotyping techniques by indicating when one should reject a new method, outright replace an old method or conditionally use a new method.
Western and non-western leadership styles and employee wellbeing: a case of a high-power distance context
Authors: Ehrnrooth Mats , Koveshnikov Alexei , Balabanova Evgeniya , Wechtler Heidi
Published: January 2024

The study combines an emic and etic perspective to test the relationships between three different (Western and non-Western) leadership styles, that is, transformational, authoritarian, and benevolent paternalistic, and follower emotional exhaustion in a high-power distance context of Russia. It employs hierarchical linear modeling (HLM) to analyse a sample of 403 followers to middle-level managers in Russian organizations. The analysis finds only transformational leadership to be generally negatively associated with emotional exhaustion. However, under conditions of high individual-level power distance orientation among followers, this association diminishes whereas that of authoritarian leadership and exhaustion increases. Benevolent paternalistic leadership is unrelated to emotional exhaustion. The study extends research on the relative importance of Western and non-Western leadership behaviors for employee wellbeing in high-power distance contexts and on how this importance differs across followers, thus highlighting the role of follower expectations in determining the effectiveness of leadership. It points toward the need for future research to simultaneously test the contingencies and relative importance of paternalistic, authoritarian, transformational, as well as other leadership styles in various cultures as well as to continue exploring the moderating influence of various cultural value orientations on these leadership styles’ follower effects.
Health beliefs and attitudes toward Influenza and COVID-19 vaccination in Portugal: a study using a mixed-method approach
Authors: Santos Ana João , Kislaya Irina , Matias-Dias Carlos , Machado Ausenda
Published: January 2024

Introduction

Vaccination is one of the most effective population strategies to prevent infectious diseases and mitigate pandemics, and it is important to understand vaccine uptake determinants since vaccine hesitancy has been increasing for the past few decades. The Health Belief Model (HBM) has been widely used for understanding vaccination behavior. The current study aimed to assess influenza vaccine (IV) non-uptake and attitudes toward COVID-19 vaccination, two important respiratory diseases with similar symptoms, and routes of transmission in the Portuguese population.

Methods

We conducted a cross-sectional study using a panel sample of randomly chosen Portuguese households. A total of 1,050 individuals aged 18 years and over responded to a telephone or online questionnaire. Through a mixed-method approach, we employed thematic content analysis to describe reasons for not taking the IV, considering the HBM dimensions, and quantitative statistical analysis to estimate IV and COVID-19 vaccine coverage.

Results

The IV uptake for the overall population was 30.7% (CI 95%: 26.5, 35.2). Susceptibility was found to be a main factor for IV non-uptake, followed by barriers, such as stock availability and fear of adverse effects. The uptake of the COVID-19 vaccine was very high in the study population (83.1%, CI 95%: 13.6%−20.9%). There was a high perception of COVID-19-associated severity and fear of the consequences. Individuals who reported IV uptake seemed to perceive a higher severity of COVID-19 and a higher benefit of taking the COVID-19 vaccine for severe complications.

Discussion

Thus, the population does not seem to consider influenza to be a health risk, as opposed to COVID-19, which is considered to be a possibly severe disease. The association between IV uptake and COVID-19 perceptions highlights that an overall attitude toward vaccination in general may be an important individual determinant.
Roles of ribosomal RNA in health and disease
Authors: Johnston Ryan , Aldrich Anne , Lyons Shawn M.
Published: January 2024

Ribosomes are amongst the most ancient molecular machines in cells, showing conservation from the simplest prokaryotes to humans. Ribosomes are an assembly of ribosomal (r)RNA and ribosomal proteins, but the rRNA comprises most of the mass of the ribosome and performs key enzymatic tasks. In humans, rRNA undergoes a laborious maturation that involves multiple processing steps and the deposition of chemical modifications. The correct processing and modification of rRNA ensures the proper function of the mature ribosome. Disturbance of these processes may lead to human disease. Understanding the role of rRNA in protein synthesis and the consequences of its dysregulation is key to deciphering and mitigating the emergence of pathological states in human biology.
pH-dependent interactions of coacervate-forming histidine-rich peptide with model lipid membranes
Authors: Gudlur Sushanth , Ferreira Filipe Viana , Ting Javier Shu Ming , Domene Carmen , Maricar Syed , Le Brun Anton P. , Yepuri Nageshwar , Moir Michael , Russell Robert , Darwish Tamim , Miserez Ali , Cárdenas Marité
Published: January 2024

Peptide-based liquid droplets (coacervates) produced by spontaneous liquid-liquid phase separation (LLPS), have emerged as a promising class of drug delivery systems due to their high entrapping efficiency and the simplicity of their formulation. However, the detailed mechanisms governing their interaction with cell membranes and cellular uptake remain poorly understood. In this study, we investigated the interactions of peptide coacervates composed of HBpep—peptide derived from the histidine-rich beak proteins (HBPs) of the Humboldt squid—with model cellular membranes in the form of supported lipid bilayers (SLBs). We employed quartz crystal microbalance with dissipation monitoring (QCM-D), neutron reflectometry (NR) and atomistic molecular dynamics (MD) simulations to reveal the nature of these interactions in the absence of fluorescent labels or tags. HBpep forms small oligomers at pH 6 whereas it forms µm-sized coacervates at physiological pH. Our findings reveal that both HBpep oligomers and HBpep-coacervates adsorb onto SLBs at pH 6 and 7.4, respectively. At pH 6, when the peptide carries a net positive charge, HBpep oligomers insert into the SLB, facilitated by the peptide’s interactions with the charged lipids and cholesterol. Importantly, however, HBpep coacervate adsorption at physiological pH, when it is largely uncharged, is fully reversible, suggesting no significant lipid bilayer rearrangement. HBpep coacervates, previously identified as efficient drug delivery vehicles, do not interact with the lipid membrane in the same manner as traditional cationic drug delivery systems or cell-penetrating peptides. Based on our findings, HBpep coacervates at physiological pH cannot cross the cell membrane by a simple passive mechanism and are thus likely to adopt a non-canonical cell entry pathway.