bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic biology approaches to negative emissions technologies: a technological and ethical appraisal
Authors: Logel Dominic Y. , Wodak Josh
Published: January 2025

This article explores the impact that synthetic biology approaches may have on Negative Emissions Technologies (NETs). Synthetic biology has both altered and created biological pathways inspired by nature to develop new NETs that sequester greenhouse gases into industrially useful chemicals, such as biomass and calcium carbonate. However, synthetic biology continues to encounter difficulties when implementing and scaling up production due to a combination of hard limits (within biology) and ‘soft’ limits (of social and economic costs). Additionally, NETs, along with Ecosystem Technologies in general, operate as climate technofixes, wherein insufficient thought is given to the ethical quandaries arising from releasing designed organisms into the environment, even under controlled conditions. In this paper, we provide a technological and ethical appraisal of synthetic biology approaches to NETs, in the context of climate change mitigation through Ecosystem Technology.
Three-dimensional electrical structure in the northwestern sector of the Sichuan-Yunnan diamond block
Authors: Zhang Yunyun , Chen Xiaobin , Wang Peijie , Cai Juntao , Liu Zhongyin , Zhang Jiong , Huang Xingxing
Published: January 2025

The Sichuan-Yunnan diamond block is a significant region of material flow from the Tibetan Plateau. However, its northwest electrical boundary remains undefined. Our study conducted a magnetotelluric profile from Chazha to Luomai across the geological boundary of the Sichuan-Yunnan block in its northwest sector. Using the nonlinear conjugate gradient three-dimensional inversion method, we obtained the deep electrical structure across the northern part of the block. Our findings reveal distinct segmental characteristics in the electrical structure along the profile. Marked by a high-resistivity zone along the Dedeng-Batang-Riyu fault, two high-conductivity layers exist in the upper-middle crust of the southwestern and central sections of the profile, at depths of 5–20 km and 10–30 km, respectively. Thus, our study suggests that the northwest boundary of the Sichuan-Yunnan diamond block, contrary to previous studies that considered it a transitional boundary, is located at the Dedeng-Batang-Riyu fault. Here, the boundary is a high-resistivity barrier, electrically isolating the Qiangtang block in the southwest from the Sichuan-Yunnan block in the northeast. The two significant high-conductivity zones in the upper-middle crust appear within the block’s interior, contrasting with previous assumptions of lower crustal flow.
Socratic wisdom in the age of AI: a comparative study of ChatGPT and human tutors in enhancing critical thinking skills
Authors: Fakour Hoda , Imani Moslem
Published: January 2025

Introduction

This study investigates the perceptual differences between ChatGPT and human tutors in fostering critical thinking among students, highlighting the effectiveness of Socratic tutoring methodologies in modern educational contexts.

Methods

Conducted with a sample of 230 university students in Taiwan, the research employed a mixed-methods approach, combining quantitative surveys and qualitative interviews.

Results and discussion

Results reveal that while a significant portion of students appreciates the benefits of ChatGPT—namely its non-judgmental nature and accessibility—human tutors are acknowledged for their capability to provide tailored feedback and emotional support. Through threshold analysis conducted via a Multilayer Perceptron (MLP) model, the study identified key features affecting student preferences, emphasizing the need for a balanced integration of AI and human tutoring methods. Findings underscore the importance of developing hybrid educational models that leverage both the strengths of human facilitators and the efficiencies of AI tools to enhance student learning and critical thinking skills.
Diagnosis and management of type 2 diabetes mellitus in patients with ischaemic heart disease and acute coronary syndromes - a review of evidence and recommendations
Authors: Shah Muhammad Usman , Roebuck Alun , Srinivasan Bala , Ward Joanna Kate , Squires Paul Edward , Hills Claire Elizabeth , Lee Kelvin
Published: January 2025

Type 2 diabetes mellitus (T2DM) represents a major healthcare condition of the 21st century. It is characterised by persistently elevated blood glucose occurring as a result of peripheral insulin resistance and reduced insulin production which may lead to multiple long-term health conditions such as retinopathy, neuropathy, and nephropathy. The estimated number of individuals suffering from diabetes mellitus (DM) is expected to rise to 591 million by the year 2035 with 4.4 million in the United Kingdom (UK) alone, 90% of which is attributed to T2DM. Moreover, a significant proportion of individuals may have undetected diabetes mellitus, especially among those presenting with symptoms of ischaemic heart disease (IHD). This is particularly important in those individuals presenting with acute coronary syndromes (ACS) who are at the highest risk of complications and sudden cardiac death. Identifying abnormal levels of common biochemical markers of diabetes, such as capillary blood glucose or glycated haemoglobin (HbA1c) in these patients is important for early diagnosis, which will then allow for timely intervention to improve outcomes. However, a significant proportion of individuals who meet the criteria for the diagnosis of diabetes remain undiagnosed, representing missed opportunities for early intervention. This may result in a prolonged period of untreated hyperglycaemia, which can result resulting in significant further microvascular and macrovascular complications. There is an increased risk of IHD, heart failure, cerebrovascular accidents (CVA), and peripheral artery disease (PVD). These account accounting for 50% of deaths in patients with T2DM. Cardiovascular diseases in the context of diabetes particular represent a significant cause of morbidity and mortality with a two to three times higher risk of cardiovascular disease in individuals with T2DM than in those without the condition normo-glycaemia. In the United Kingdom UK alone, around 120 amputations, 770 CVA, 590 heart attacks, and more than 2300 presentations with heart failure per week are attributed to diabetes DM. with One 1 in six 6 hospital beds and around 10% of the healthcare budget may be being spent on managing diabetes DM or its complications. Therefore, it represents a significant burden on our healthcare system.
Decision making about increased building automation – barriers, drivers and motivation factors
Authors: Lane Anna-Lena , Selhammer Andreas , Thollander Patrik , Cehlin Mathias
Published: January 2025

Energy efficiency has been identified as a way of addressing the need to reduce climate impact from fossil fuels. Furthermore, the ongoing twin transition may provide better and more energy-efficient control of buildings with systems such as building management systems (BMS). However, there appear to be barriers to investments in functional digital tools, as there are for other energy-efficient technologies for buildings. This paper is based on a questionnaire study with technology providers, decision makers and users of building management systems. The questionnaire included questions regarding barriers, drivers, and motivations for investments in BMS. Improved energy efficiency was found to be an important motivation for investments in BMS for users and decision makers, but the technology providers elevated more easy work as important. The main driver for investments in BMS was related to reduced energy costs, while for the decision makers, financial barriers such as risks and hidden cost were ranked highest. An important knowledge barrier was found as knowledge is needed for decisions about investments, use of BMS and decisions regarding IT security, such as handling of data. A key conclusion is the need for a facilitator, as knowledge is needed for decisions about BMS investments and for its use. On a broader scale, the paper argues for the need to include facilitators as a core part of future policies within the twin transition.
Machine learning potential predictor of idiopathic pulmonary fibrosis
Authors: Ding Chenchun , Liao Quan , Zuo Renjie , Zhang Shichao , Guo Zhenzhen , He Junjie , Ye Ziwei , Chen Weibin , Ke Sunkui
Published: January 2025

Introduction

Idiopathic pulmonary fibrosis (IPF) is a severe chronic respiratory disease characterized by treatment challenges and poor prognosis. Identifying relevant biomarkers for effective early-stage risk prediction is therefore of critical importance.

Methods

In this study, we obtained gene expression profiles and corresponding clinical data of IPF patients from the GEO database. GO enrichment and KEGG pathway analyses were performed using R software. To construct an IPF risk prediction model, we employed LASSO-Cox regression analysis and the SVM-RFE algorithm. PODNL1 and PIGA were identified as potential biomarkers associated with IPF onset, and their predictive accuracy was confirmed using ROC curve analysis in the test set. Furthermore, GSEA revealed enrichment in multiple pathways, while immune function analysis demonstrated a significant correlation between IPF onset and immune cell infiltration. Finally, the roles of PODNL1 and PIGA as biomarkers were validated through in vivo and in vitro experiments using qRT-PCR, Western blotting, and immunohistochemistry.

Results

These findings suggest that PODNL1 and PIGA may serve as critical biomarkers for IPF onset and contribute to its pathogenesis.

Discussion

This study highlights their potential for early biomarker discovery and risk prediction in IPF, offering insights into disease mechanisms and diagnostic strategies.
A new weapon: the application of tumor vaccines based on extracellular exosomal heat shock proteins in immunotherapy
Authors: Yi Kexin , Sun Chengpeng , Yuan Yalin , Luo Zhaowei , Luo Hongliang , Xie Yunhe
Published: January 2025

Despite the significant advancements in cancer research, innovative approaches are still needed to reduce tumor incidence, progression, and dissemination, as well as for prolonging patient survival. Currently, the development of cancer vaccines is gaining attention as a novel preventative and therapeutic strategy. Although the concept of cancer vaccination is not new, a limited number of vaccines have received approval for tumor therapy. Heat shock protein (HSP)-based vaccination represents a promising strategy that harnesses specific tumor antigens to activate immune responses. Exosomes (Exs) are highly heterogeneous bilayer vesicles capable of transporting various types of molecules through extracellular space. Compared with conventional anticancer drugs, exosomes exhibit low toxicity and good biocompatibility, and they can stimulate the immune system either directly or indirectly. Ex-based vaccines may elicit an antitumor immune response that generates memory cells capable of recognizing cancer antigens, thereby inhibiting disease progression. This paper reviews the potential applications of HSPs and exosomes in the prevention and treatment of solid tumors. Finally, we discuss the advantages of the extracellular exosomal heat shock protein (HSP-Ex1) vaccine and future research directions aimed at optimizing heat shock protein-based cancer immunotherapy strategies.
Exploring the effects of dietary methionine supplementation on European seabass mucosal immune responses against Tenacibaculum maritimum
Authors: Carvalho Inês , Peixoto Diogo , Ferreira Inês , Robledo Diego , Ramos-Pinto Lourenço , Silva Rodolfo Miguel , Gonçalves José Fernando , Machado Marina , Tafalla Carolina , Costas Benjamin
Published: January 2025

Introduction

Dietary methionine supplementation has been shown to enhance immunity and disease resistance in fish. However, excessive intake may lead to adverse effects. The present study aimed to evaluate the immune status of European seabass (Dicentrarchus labrax) fed increasing levels of dietary methionine supplementation and to investigate the early immune response to Tenacibaculum maritimum.

Methods

For this purpose, juvenile European seabass were fed one of three experimental diets containing methionine at 8.6 mg/g (CTRL), 18.5 mg/g (MET2), and 29.2 mg/g (MET3) for four weeks, followed by a bath challenge with T. maritimum.

Results

While higher methionine intake reduced hemoglobin levels, no other significant changes in the immune status were observed. However, after infection, fish fed higher methionine levels exhibited a dose-dependent decrease in the mRNA expression of some proinflammatory genes. Similarly, RNA sequencing analysis of skin tissue revealed an attenuated immune response in the MET2 group at 24 hours post-infection, with few proinflammatory genes upregulated, which intensified at 48 h, potentially due to advanced tissue colonization by T. maritimum. The MET3 group displayed the least pronounced immune response, along with the enrichment of some immune-related pathways among the downregulated transcripts. These findings, together with the lower mRNA expression of proinflammatory genes in the head kidney and the higher mortality rates observed in this group, suggest a potential impairment of the immune response.`

Discussion

Overall, these findings indicate that dietary methionine supplementation may significantly influence both systemic and local immune responses in European seabass, highlighting the need for careful consideration when supplementing diets with methionine.
Identification of circulating Tfh/Th subsets as a biomarker of developed hospital-acquired pneumonia
Authors: Peng Yuan , Tao Tao , Yu Ni-Wen , Xu Chenyang , Chen Cheng
Published: January 2025

Background

This study aimed to explore the possible value of follicular helper T (Tfh) cells in hospital-acquired pneumonia (HAP).

Methods

Flow cytometry was used to measure circulating Tfh and helper T cell (Th) cells in 62 HAP patients and 16 healthy individuals. HAP patients were further categorized into uncontrolled and controlled groups, in accordance with relevant guidelines. Subgroup analyses were additionally conducted based on the pathogen and the presence of bloodstream infections (BSIs) and the incidence of septic shock. Kaplan-Meier survival analysis and ROC analysis were performed to estimate the prognostic value of the combination of Tfh/Th ratios and PCT levels.

Results

The Tfh/Th ratio was notably higher in uncontrolled HAP patients than in controls (P<0.05). Specifically, either the Klebsiella pneumoniae (K.p) -positive HAP or BSIs subgroups or septic shock subgroups showed significantly increased Tfh/Th ratios (P<0.05). PCT level in BSIs and septic shock subgroups was significantly increased. However, there were no significant differences in PCT level between K.p-infected and non-K.p-infected patients. So, the Tfh/Th ratio is a good supplement to PCT for distinguishing between the K.p and non-K.p groups. The Tfh/Th ratio also demonstrated a strong correlation with procalcitonin (PCT) levels (P<0.05). Accordingly, the combination of Tfh/Th and PCT could serve as a more effective predictive marker for HAP deterioration and survival prediction. HAP patients with a high Tfh/Th ratio along with high PCT levels had a lower 28-day survival rate.

Conclusion

The circulating Tfh/Th ratio, instrumental in gauging the severity of patients with HAP, could be employed as a prognostic biomarker for HAP.
Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
Authors: Yang Yang , Hong Qing , Zhang Xuehong , Liu Zhenmin
Published: January 2025

Background

Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Numerous clinical studies have indicated a correlation between alterations in gut microbiota and the onset and progression of RA. This research aims to restore intestinal microbiota to a healthy state through the oral administration of Bifidobacterium in the early stages with the goal of delaying the onset and progression of RA.

Methods

Collagen-induced arthritis (CIA) rat model was constructed to assess the development of RA using arthritis clinical scores, paw thickness, pathological analysis of knee joint. The immune response was evaluated by determinating specific antibodies and cytokines in serum and synovial fluid. The expression of intestinal barrier protein was analyzed by qPCR to evaluate the intestinal barrier function. Alterations in gut microbiota and metabolites were assessed by 16S rDNA and non-targeted metabolomics.

Results

The findings reveal that administering Bifidobacterium animalis BD400 orally led to a significant reduction in arthritis clinical scores and paw swelling thickness in CIA rats. Additionally, there was a decrease in osteo-facial fusion and calcified cartilage thickening in the knee joint. Furthermore, the oral administration of B. animalis BD400 resulted in the down-regulation of inflammatory factors TNF-α and collagenase MMP-13 in the knee joint. Levels of specific antibodies (anti-CII IgG, anti-CII IgG1, and anti-CII IgG2a) and cytokine IL-17A in serum, as well as cytokines (TNF-α and IL-1β) in the synovial fluid of B. animalis BD400-treated CIA rats, were significantly reduced (p < 0.05). The gene expression levels of intestinal barrier proteins (occludin-1, MUC-2, and ZO-1) showed a significant increase (p < 0.05) in B. animalis BD400-treated CIA rats. The oral administration of B. animalis BD400 altered the composition of intestinal microorganisms in CIA rats at the phylum and genus levels, particularly affecting the genus HT002. B. animalis BD400 alleviates RA by down-regulating 1-methyl-L-histidine and urocanate in the histidine metabolism, laying a foundation for the RA prevention.

Conclusion

By affecting genus HT002 and histidine metabolism in the gut microbiota of CIA rats, B. animalis BD400 restored intestinal permeability, inhibited systemic inflammatory response, and ultimately slowed down the development of RA.
Bayesian Optimization of insect trap distribution for pest monitoring efficiency in agroecosystems
Authors: Yanchenko Eric , Chappell Thomas M. , Huseth Anders S.
Published: January 2025

Insect trap networks targeting agricultural pests are commonplace but seldom optimized to improve precision or efficiency. Trap site selection is often driven by user convenience or predetermined trap densities relative to sensitive host crop abundance in the landscape. Monitoring for invasive pests often requires expedient decisions based on dispersal potential and ecology to inform trap placement. Optimization of trap networks using contemporary analytical approaches can help users determine the distribution of traps as information accumulates and priorities change. In this study, a Bayesian optimization (BO) algorithm was used to learn more about the optimal distribution of a fine-scale trap network targeting Helicoverpa zea (Boddie), a significant agricultural pest across North America. Four years of pheromone trap monitoring was conducted at the same 21 locations distributed across ~7,000 square kilometers in a five-county area in North Carolina, USA. Three years of data were used to train a BO model with a fourth year designated for testing. For any quantity of trap locations, the approach identified those that provide the most information, allowing optimization of trapping efficiency given either a constraint on the number of locations, or a set precision required for pest density estimation. Results suggest that BO is a powerful approach to enable optimized trap placement decisions by practitioners given finite resources and time.
Shining light on knee osteoarthritis: an overview of vitamin D supplementation studies
Authors: Zhang Di , Ye Miaoyu , Xu Yao , Jiang Luyu , Hu Yanmei , Zhang Qi , Han Xiao , Dai Qian , Qian Junhui , Luo Jian , Yuan Qiang
Published: January 2025

Background

The impact of knee osteoarthritis on individuals’ daily functioning is significant. In recent years, Vitamin D supplements cure osteoarthritis has garnered attention from medical professionals and patients due to its simplicity and portability. Several systematic reviews (SRs) and meta-analyses (MAs) have examined the efficacy of vitamin D supplementation for knee osteoarthritis, yet there is variability in their methodology and quality.

Objective

To search, gather, and analyze data on the characteristics and quantitative results of SR/MA in patients with KOA treated with Vitamin D supplementation, and objectively evaluate the efficacy of supplements. Then, provides clinical evidence and recommendations the clinical use of vitamin D supplementation.

Methods

Two individuals reviewed and collected data from four databases until October 2023. AMSTAR-2, ROBIS, PRISMA 2020, and GRADE tools were used to evaluate the methodological quality, bias risk, reporting quality, and evidence strength of all SR/MA. Additionally, we applied the corrected covered area (CCA) method to measure overlap in randomized controlled trials (RCTs) cited among the SR/MA.

Results

3 SRs and 6 MAs were included in the analysis: 3 studies were low quality by AMSTAR-2, and 6 studies were very low quality. According to ROBIS, 6 studies were high-risk and 3 were low-risk. In PRISMA 2020 reporting quality, most studies showed deficiencies in comprehensive literature search strategy, reasons for literature exclusion, data preprocessing for meta-analysis, exploration of reasons for heterogeneity, sensitivity analysis, publication bias, and disclosure of funding and conflicts of interest. Grading the quality of evidence in GRADE consisted of 5 items of moderate quality, 14 items of low quality, and 10 items of very low quality. Bias risk and imprecision were the main factors for downgrading. The calculation of RCT overlap between SR/MA using CCA showed a high degree of overlap.

Conclusion

Vitamin D supplementation may show potential efficacy in ameliorating symptoms of KOA. The evidence indicates that Vitamin D supplements for knee osteoarthritis can improve patients’ Total WOMAC scores and synovial fluid volume in the joints. Nevertheless, due to the generally low quality of current studies, future research should prioritize improving the quality of primary studies to establish the efficacy of vitamin D supplementation for KOA with more robust scientific evidence.

Systematic review registration

The protocol of this overview was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (https://www.crd.york.ac.uk/PROSPERO/) with the registration number CRD42024535841.
Non-invasive methods for diagnosing portal hypertension and variceal bleeding due to liver cirrhosis secondary to NAFLD/MASLD: systematic review
Authors: Shanka Nebyu Yonas , Pavlov Chavdar S. , Mekonnen Nigatu Leul
Published: January 2025

Background

Non-alcoholic fatty liver disease (NAFLD), recently re-termed as metabolic dysfunction-associated steatotic liver disease (MASLD), is a global health concern affecting approximately 25% of adults. Complications such as portal hypertension and variceal bleeding are critical to diagnose but challenging with traditional invasive methods like hepatic venous pressure gradient (HVPG) measurement and esophagogastroduodenoscopy (EGD), which are not always feasible and carry risks.

Objectives

This systematic review aim to evaluate the diagnostic accuracy of non-invasive methods for diagnosing portal hypertension and variceal bleeding in patients with NAFLD/MASLD cirrhosis, comparing these methods to invasive standards.

Methods

A comprehensive literature search was conducted across PubMed, Cochrane Library, Google Scholar, and ScienceDirect from January 2000 to May 2024. Studies included evaluated non-invasive diagnostic techniques for portal hypertension and variceal bleeding, compared with HVPG and EGD, focusing on adult patients with confirmed NAFLD/MASLD cirrhosis. Data extraction covered study characteristics and diagnostic accuracy metrics. The quality of studies was assessed using the QUADAS-2 tool. Meta-analyses were performed using R and Python.

Results

Eleven studies involving 2,707 patients met the inclusion criteria. Liver stiffness measurement (LSM) via transient elastography demonstrated high sensitivity (85%) and specificity (79%) for diagnosing clinically significant portal hypertension (CSPH) at a 20 kPa cutoff. For severe portal hypertension (SPH), LSM had a sensitivity of 81% and specificity of 85% at 25 kPa. Combining LSM with platelet count resulted in a sensitivity of 97% but lower specificity (41%) for CSPH. Spleen stiffness measurement (SSM) also showed good diagnostic performance with a sensitivity of 89% and specificity of 75% for CSPH.

Conclusion

Non-invasive tests, particularly LSM and SSM, show promise in diagnosing portal hypertension and variceal bleeding in NAFLD/MASLD cirrhosis. These methods offer high sensitivity, especially in combination, supporting their use in clinical settings to potentially reduce the need for invasive procedures. Future research should aim to standardize protocols and explore additional biomarkers to further enhance diagnostic accuracy.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42024567024.
Effect of a high dose atorvastatin as adjuvant therapy to mesalamine in attenuating inflammation and symptoms in patients with ulcerative colitis: a randomized controlled pilot study
Authors: Alarfaj Sumaiah J. , El-Haggar Sahar M. , Hegazy Sahar K. , Maher Maha M. , Bahgat Monir M. , Elmasry Thanaa A. , Alrubia Sarah , Alsegiani Amsha S. , Bahaa Mostafa M.
Published: January 2025

Background

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon. Several preclinical studies investigated the beneficial effects of atorvastatin in colitis. Activation of sphingosine 1 phosphate (S1P)/ tumor necrosis factor-alpha (TNF-α)/ interleukin-6 (IL-6) pathways has been confirmed in the pathogenesis of UC and preclinical studies proved the efficacy of atorvastatin on these pathways.

Aim

To investigate the role of atorvastatin on S1P/TNF-α/IL-6 pathway in UC.

Methods

Patients with mild to moderate UC were allocated into two groups in this pilot study. For 6 months, Group 1 (placebo group) received both a placebo and 1 g of mesalamine three times daily (t.i.d.). Group 2, (the atorvastatin group) received atorvastatin 80 mg once daily and 1 g of mesalamine t.i.d. A gastroenterologist evaluated the patients’ colitis severity by partial Mayo score index (PMS). Serum IL-6, S1P, TNF-α, nitric oxide (NO), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin were measured before and after treatment. Short Form 36 questionnaire (SF-36) was also assessed. A clinical response was defined as a decline in the rectal bleeding sub score of at least one point, and a decrease in PMS of at least two points. Clinical remission was defined as a PMS of less than 2 and the absence of any single sub score greater than 1.

Primary outcome

Decreased PMS and improved quality of life.

Secondary outcome

Change in the level of measured biomarkers.

Results

Compared to the placebo group (n = 24), the atorvastatin group (n = 23) exhibited a significant decrease in the level of IL-6 (p = 0.001), S1P (p = 0.0001), TNF-α (p = 0.003), NO (p = 0.0001), CRP (p = 0.015), ESR (p = 0.012), PMS (p = 0.013), and fecal calprotectin (p = 0.0003), and improved SF-36 (p = 0.006). In placebo group, the response rate was 83.33% (n = 20/24) for PMS, and the remission rate was 45.83% (n = 11/24). In the atorvastatin group, the response rate was 91.3% (n = 21/23), and the remission rate was 60.8% (n = 14/23) for PMS.

Conclusion

Atorvastatin could be an adjunctive therapy for patients with UC.

Clinical trial registration

https://www.clinicaltrials.gov/, Identifier NCT05561062.
Diverse clinical manifestations and prognosis in a couple’s mercury poisoning caused by skin-lightening creams: two case reports and literature review
Authors: Ji Huixia , Chen Ye , Liu Dandan , Zhou Tongzhou , Tang Yuhua
Published: January 2025

Skin exposure to mercury-containing creams occurs most commonly in young and middle-aged women and, in a few cases, in men. This article presents the symptoms and prognosis of a couple who developed mercury poisoning after cosmetic use of similar duration and dosage. Case 1 is a 33-year-old man who developed nephrotic syndrome after using skin-lightening creams containing mercury over 9 months. Renal puncture pathology indicated membranous nephropathy. During the course of the illness, the patient intermittently took Chinese medicine. Approximately 4 months later, the patient developed pulmonary thrombosis and lower extremity venous thrombosis as a result of fatigue driving and had to undergo thrombolysis and filter implantation. A urine mercury level of 65.4 μg/g·creatinine was detected in the patient. The urine protein level remained positive 8 months after mercury removal. Case 2 is a 30-year-old woman, the wife of case 1, who used the same creams for 9 months with her husband and had a urine mercury level of 80 μg/g·creatinine. The patient experienced sleep disturbances, fatigue, and irritability. In Case 2, neurasthenia symptoms were relieved following mercury removal, and no other complications were observed. There have been very few reports regarding male patients developing nephrotic syndrome as a consequence of using cosmetics that contain mercury. However, clinicians should not neglect this cause when dealing with newly diagnosed male patients with nephrotic syndrome. The treatment and prognosis of male patients are less well established, and changes in their condition must be closely monitored.
Unveiling causal immune cell–gene associations in multiple myeloma: insights from systematic reviews and Mendelian randomization analyses
Authors: Zhang Hui , Zhang Ling , Lian Jing-Xuan , Kou Zhi-Fu , Zhu Yu , Ma Li-Tian , Zheng Jin , Zhao Can-Jun
Published: January 2025

Background

The efficacy of novel chimeric antigen receptor T-cell (CAR-T) therapy is inconsistent, likely due to an incomplete understanding of the tumor microenvironment (TME). This study utilized meta-analysis to evaluate CAR-T-cell therapy efficacy and safety and employed two-sample Mendelian randomization (MR) analysis to investigate the causal links between immune cells and Multiple Myeloma (MM).

Method

Our literature review, conducted from January 1, 2019, to August 30, 2024, across Medline/PubMed, Scopus, and Web of Science, identified 2,709 articles, 34 of which met our inclusion criteria. We utilized MR analysis of GWAS data to identify immune cells causally related to multiple myeloma, followed by SMR analysis to highlight associated pathogenic genes and colocalisation analysis for validation.

Results

The meta-analysis revealed an 82.2% overall response rate to CAR-T-cell therapy, characterized by a safe profile with a grade 3 or higher CRS of 6.3% and neurotoxicity of 0.9%. BCMA, CD38, and GPRC5D CAR-T-cell therapies had superior response rates, whereas BCMA and CD3 CAR-T-cell therapy rates lagged at 61.8%. Post-adjustment for multiple testing, the levels of seven types of immune cells (two types of Treg, two types of TNBK, two types of B cells, and one type of Myeloid cell) were found to be elevated in association with an increased risk of multiple myeloma (MM), while the levels of another eight types of immune cells (one types of Treg, three types of TNBK, one type of MT cells, and two types of Myeloid cell and one type of cDC cells) were demonstrated to be associated with a decreased risk of MM. As supported by sensitivity analysis. SMR analysis pinpointed the risk genes VDR, VHL, POMC, and FANCD2, with VHL and POMC correlating at the methylation level. VDR was not significantly correlated with MM after correction for multiple tests. NCAM1 also exhibited a significant methylation-level association with disease.

Conclusion

Our study supports the efficacy and safety of CAR-T-cell therapy in rrMM patients, with an 82.2% ORR and low rates of severe CRS (6.3%) and neurotoxicity (0.9%). This finding also suggests that BCMA/CD19 bispecific CAR-T cells have a superior ORR, pending clinical confirmation. MR analysis reveals links between immune cells, genes such as VDR and VHL, and MM, enhancing our understanding of its pathophysiology.
Global insights into MRSA bacteremia: a bibliometric analysis and future outlook
Authors: Lin Jia-Yi , Lai Jia-Kai , Chen Jian-Yi , Cai Jia-Yu , Yang Zhan-Dong , Yang Liu-Qingqing , Zheng Ze-Tao , Guo Xu-Guang
Published: January 2025

Background

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) pose a significant challenge to global public health, characterized by high morbidity and mortality rates, particularly in immunocompromised patients. Despite extensive research, the rapid development of MRSA antibiotic resistance has outpaced current treatment methods, increasing the difficulty of treatment. Therefore, reviewing research on MRSA BSIs is crucial.

Methods

This study conducted a bibliometric analysis, retrieving and analyzing 1,621 publications related to MRSA BSIs from 2006 to 2024. The literature was sourced from the Web of Science Core Collection (WoSCC), and data visualization and trend analysis were performed using VOSviewer, CiteSpace, and Bibliometrix software packages.

Results

The bibliometric analysis showed that research on MRSA BSIs was primarily concentrated in the United States, China, and Japan. The United States leads in research output and influence, with significant contributions from institutions such as the University of California system and the University of Texas system. The journal with the most publications is Antimicrobial Agents and Chemotherapy, while the most cited global publication is Vincent JL’s article “Sepsis in European Intensive Care Units: Results of the SOAP Study” published in Critical Care Medicine in 2006. Cosgrove SE’s article “Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis” had the most co-citations. Key trends in the research include MRSA’s antibiotic resistance mechanisms, the application of new diagnostic technologies, and the impact of COVID-19 on MRSA studies. Additionally, artificial intelligence (AI) and machine learning are increasingly applied in MRSA diagnosis and treatment, and phage therapy and vaccine development have become future research hotspots.

Conclusion

Methicillin-resistant Staphylococcus aureus BSIs remain a major global public health challenge, especially with the increasing severity of antibiotic resistance. Although progress has been made in new treatments and diagnostic technologies, further validation is required. Future research will rely on integrating genomics, AI, and machine learning to drive personalized treatment. Strengthening global cooperation, particularly in resource-limited countries, will be key to effectively addressing MRSA BSIs.
Optimal trajectory of the neuroendoscope for third ventricle pavement access
Authors: Sousa Joana , Silva Susana Maria , Alves Hélio , Carvalho Bruno , Sousa José Maria , Ferreira-Pinto Manuel J. , Andrade José Paulo
Published: January 2025

Background and aim

Endoscopic Third Ventriculostomy (ETV) is used to treat hydrocephalus, an abnormal cerebrospinal fluid accumulation in brain ventricles. By defining a new trajectory and entry point interval, we aim to establish a standardized approach for FreeHand ETV, a vital technique when specialized tools are unavailable, or during emergencies.

Methods

187 MRIs were analyzed, with 30 having hydrocephalus. A pathway crossing the cranial bone, interventricular foramen (of Monro) and tuber cinereum was outlined. Measurements involved distances to cranial sutures, pathway angles and depths, and distances to important anatomical landmarks. Comparisons between hydrocephalic and non-hydrocephalic patients were made while assessing variations linked to age, sex and Evan’s index.

Results

Significant differences were found, notably for depth (93.520 ± 7.228 mm), coronal plane angulation (10.982° ± 6.119°), distance to the sagittal suture (18.957 ± 8.608 mm), and distance to the superior frontal sulcus (7.00 mm). Other variables did not differ significantly between groups, including for the sagittal plane angulation (2.549° ± 3.576°) and the distances to the precentral sulcus (19.93 ± 7.955 mm), and to the coronal suture (10.55 mm).

Conclusion

The new approach, situated close to cranial sutures and distant to the precentral and superior frontal sulcus, shows promise in enhancing surgical precision and outcomes for hydrocephalus management.
Distinct sex differences in ethanol consumption and operant self-administration in C57BL/6J mice with uniform regulation by glutamate AMPAR activity
Authors: Faccidomo Sara , Eastman Vallari R. , Santanam Taruni S. , Swaim Katarina S. , Taylor Seth M. , Hodge Clyde W.
Published: January 2025

Introduction

Considering sex as a biological variable (SABV) in preclinical research can enhance understanding of the neurobiology of alcohol use disorder (AUD). However, the behavioral and neural mechanisms underlying sex-specific differences remain unclear. This study aims to elucidate SABV in ethanol (EtOH) consumption by evaluating its reinforcing effects and regulation by glutamate AMPA receptor activity in male and female mice.

Methods

C57BL/6J mice (male and female) were assessed for EtOH intake under continuous and limited access conditions in the home cage. Acute sensitivity to EtOH sedation and blood clearance were evaluated as potential modifying factors. Motivation to consume EtOH was measured using operant self-administration procedures. Sex-specific differences in neural regulation of EtOH reinforcement were examined by testing the effects of a glutamate AMPA receptor antagonist on operant EtOH self-administration.

Results

Female C57BL/6J mice exhibited a time-dependent escalation in EtOH intake under both continuous and limited access conditions. They were less sensitive to EtOH sedation and had lower blood levels post-EtOH administration (4 g/kg) despite similar clearance rates. Females also showed increased operant EtOH self-administration and progressive ratio performance over a 30-day baseline period compared to males. The AMPAR antagonist GYKI 52466 (0–10 mg/kg, IP) dose-dependently reduced EtOH-reinforced lever pressing in both sexes, with no differences in potency or efficacy.

Discussion

These findings confirm that female C57BL/6J mice consume more EtOH than males in home-cage conditions and exhibit reduced acute sedation, potentially contributing to higher EtOH intake. Females demonstrated increased operant EtOH self-administration and motivation, indicating higher reinforcing efficacy. The lack of sex differences in the relative effects of GYKI 52466 suggests that AMPAR activity is equally required for EtOH reinforcement in both sexes.
A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
Authors: Lipshutz Allie , Saltz Victoria , Anderson Kristin R. , Manganaro Alessia , Dumitriu Dani
Published: January 2025

Introduction

The neurobiological basis for individual variability in behavioral responses to stimuli remains poorly understood. Probing the neural substrates that underlie individual variability in stress responses may open the door for preventive approaches that use biological markers to identify at-risk populations. New developments of viral neuronal tracing tools have led to a recent increase in studies on long range circuits and their functional role in stress responses and social behavior. While these studies are necessary to untangle largescale connectivity, most social behaviors are mediated and fine-tuned by local subregional circuitry.

Methods

In order to probe this local, interregional connectivity, we present a new combination of a neuronal tracing system with immediate early gene immunohistochemistry for examining structural and functional connectivity within the same animal. Specifically, we combine a retrograde transsynaptic rabies tracing system with cFos colocalization immediately after an acute stressor to elucidate local structural and stress-activated connectivity within the amygdala complex in female and male mice.

Results and discussion

We show how specific structural and functional connections can predict individual variability along a spectrum of social approach/avoidance following acute social defeat stress. We demonstrate how our robust method can be used to elucidate structural and functional differences in local connectivity that mediate individual variability in behavioral response.
Case Report: The first Korean familial case of BCAP31-related deafness, dystonia, and cerebral hypomyelination
Authors: Suh Yoong-A , Hwang Jisun , Seo Go Hun , Khang Rin , Lee Jang Hoon , Park Moon Sung , Sohn Young Bae
Published: January 2025

Deafness, dystonia, and central hypomyelination (DDCH) syndrome (OMIM #300475) is a rare X-linked genetic disorder characterized by developmental delays, deafness, central hypomyelination, and dystonia. We report the first Korean familial case involving twin boy and girl carrying a novel pathogenic BCAP31 variant which was inherited from their mother. The male proband, born prematurely with very low birth weight (VLBW), exhibited severe global developmental delay, microcephaly, failure to thrive, dystonia, seizures, sensorineural hearing loss (SNHL) requiring cochlear implantation, and mild facial dysmorphism. A brain MRI revealed white matter atrophy, thinning of the corpus callosum, and delayed myelination. The twin sister presented with mild developmental delays and bilateral SNHL but did not experience seizures or dystonia. Their mother also had bilateral SNHL. Whole genome sequencing identified a hemizygous pathogenic variant, c.247C>T (p.Gln83Ter), in the BCAP31 in the proband. The variant was also found in his mother and twin sister, who exhibited less severe symptoms. Early genetic evaluation via next-generation sequencing is crucial for timely diagnosis and intervention, particularly in VLBW infants with genetic disorders. This report expands the understanding of genotype-phenotype correlations in DDCH syndrome and highlights the variable phenotypes in manifesting females.
Clinical presentations and outcomes of celiac disease in children and adolescents at a tertiary care center in Lebanon
Authors: Andari Dana , Hanna-Wakim Rima , Khafaja Sarah , Yazbeck Nadine
Published: January 2025

Introduction

Studies on the clinical presentation of celiac disease and its impact on the growth of children in Lebanon are limited. The aim of this 10-year-retrospective study was to describe the common clinical presentations, diagnostic modalities, and the effect of the gluten-free- diet (GFD) on the growth of children and adolescents with celiac disease.

Methods

This was a retrospective chart review of subjects aged 6 months to 18 years who visited the Pediatric Gastroenterology clinic at the American University of Beirut Medical Center (AUBMC) between January 1, 2013, and June 30, 2023, and who were diagnosed with celiac disease based on serological markers and/or changes on histology of the small intestinal mucosal biopsies for those who underwent upper endoscopy, or HLA typing expressing the HLA-DQ2 or DQ8 gene for few subjects.

Results

The study included 90 patients with celiac disease, of whom 64 were newly diagnosed during the study period. The mean age at diagnosis of celiac disease was 6.93 years. Females represented 60% of the pediatric subjects with celiac disease. The most common symptoms reported were abdominal pain (51.1%), weight loss or failure to thrive (45.6%), and diarrhea (24.4%). There was a significant increase in the mean weight-for-age Z-score (WAZ) and mean body mass index (BMI)-for-age Z-score (BMIZ) 12 months following initiation of GFD; however, the change in height-for-age Z-score (HAZ) at 12 months was not statistically significant. Half of the subjects were in remission at the last clinic follow-up.

Conclusion

The most common symptoms that children with celiac disease in this cohort presented with are diarrhea, abdominal pain and failure to thrive. In this cohort, there was a significant increase in the weight parameters with no significant change in the height at 12 months after initiation of the GFD. The recognition of early manifestations, early diagnosis and strict adherence to the diet are of paramount importance to prevent long term complications.
Efferocytosis-related gene IL33 predicts prognosis and immune response and mediates proliferation and migration in vitro and in vivo of breast cancer
Authors: He Xiao , Cheng Xianjie , Zhang Zhun , Chen Lanhui , Xie Changjun , Tang Mengjie
Published: January 2025

Background

Breast cancer (BRCA) has a high incidence among women, with poor prognosis and high mortality, which is increasing year by year. Efferocytosis is a process of phagocytosis of abnormal cells and is of great value in tumor research. Our study seeks to create a predictive model for BRCA using efferocytosis-related genes (ERGs) to explore the significance of efferocytosis in this disease.

Methods

In this research, Differential analysis, and univariate Cox regression were employed to identify genes linked to prognosis in BRCA patients. Then the BRCA patients were categorized into distinct groups using consensus clustering based on prognosis genes. Survival analysis, PCA, and t-SNE were performed to verify these groups. The enrichment of metabolic pathways within the detected clusters was evaluated using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, single-sample GSEA (ssGSEA) was used to examine changes in immune infiltration and enrichment. A risk prognostic model was constructed utilizing multivariable Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analyses, and subsequently validated its predictive accuracy by stratifying patients according to the median risk score. Ultimately, some crucial independent prognostic genes were pinpointed and their expression, roles, and immune characteristics were explored in both laboratory and live models.

Results

Findings revealed 52 differentially expressed genes (DEGs), of which 21 were significantly linked to BRCA outcomes. These 21 genes were utilized for consensus clustering to categorize BRCA patients into two subtypes. Subtype B was linked to a worse prognosis compared to Subtype A, though both subtypes were distinguishable. The enriched pathways were mainly concentrated in Subtype A and were actively expressed in this group. Following this, a prognostic risk model was constructed using five risk genes, which was proven to possess significant predictive value. A significant link was identified between the immune microenvironment and the risk-associated genes and scores. IL33 was identified as an independent prognostic gene with important research value. Its in vivo expression results aligned with the data analysis findings, showing low expression in BRCA. Furthermore, overexpression of IL33 significantly inhibited BRCA growth and motility in vitro and in vivo, while also enhancing their vulnerability to destruction by activated CD8+ T cells.

Conclusion

The ERG-based risk model effectively predicts the prognosis of BRCA patients and shows a strong link with the immune microenvironment. IL33 stands out as a significant prognostic marker, crucial in the onset and advancement of BRCA. This highlights the necessity for additional studies and indicates that IL33 might be a potential target for BRCA treatment.