bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of “framework Shuffling” and “CDR Grafting” in humanization of a PD-1 murine antibody
Authors: Wang Yongmei , Chen Yi-Li , Xu Hui , Rana Gul E. , Tan Xiaorong , He Mengying , Jing Qingqing , Wang Qi , Wang Guifeng , Xie Zuoquan , Wang Chunhe
Published: July 2024

Introduction

Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans.

Methods

Two different strategies of antibody humanization are popularly employed, including “complementarity determining region (CDR) grafting” and “framework (FR) shuffling” to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies.

Results

While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background.

Discussion

The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.
Lymphocyte homing and recirculation with tumor tertiary lymphoid structure formation: predictions for successful cancer immunotherapy
Authors: Tian Weihong , Wei Wangzhi , Qin Gaofeng , Bao Xuanwen , Tong Xuecheng , Zhou Min , Xue Yuan , Zhang Yu , Shao Qixiang
Published: July 2024

The capacity of lymphocytes continuously home to lymphoid structures is remarkable for cancer immunosurveillance and immunotherapy. Lymphocyte homing and recirculation within the tumor microenvironment (TME) are now understood to be adaptive processes that are regulated by specialized cytokines and adhesion molecule signaling cascades. Restricted lymphocyte infiltration and recirculation have emerged as key mechanisms contributing to poor responses in cancer immunotherapies like chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockades (ICBs). Uncovering the kinetics of lymphocytes in tumor infiltration and circulation is crucial for improving immunotherapies. In this review, we discuss the current insights into the adhesive and migrative molecules involved in lymphocyte homing and transmigration. The potential mechanisms within the TME that restrain lymphocyte infiltration are also summarized. Advanced on these, we outline the determinates for tertiary lymphoid structures (TLSs) formation within tumors, placing high expectations on the prognostic values of TLSs as therapeutic targets in malignancies.
Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications
Authors: Tang Yi , Qu Sheng , Ning Zichao , Wu Hong
Published: July 2024

Immunopeptides have low toxicity, low immunogenicity and targeting, and broad application prospects in drug delivery and assembly, which are diverse in application strategies and drug combinations. Immunopeptides are particularly important for regulating ocular immune homeostasis, as the eye is an immune-privileged organ. Immunopeptides have advantages in adaptive immunity and innate immunity, treating eye immune-related diseases by regulating T cells, B cells, immune checkpoints, and cytokines. This article summarizes the application strategies of immunopeptides in innate immunity and adaptive immunity, including autoimmunity, infection, vaccine strategies, and tumors. Furthermore, it focuses on the mechanisms of immunopeptides in mediating ocular immunity (autoimmune diseases, inflammatory storms, and tumors). Moreover, it reviews immunopeptides’ application strategies and the therapeutic potential of immunopeptides in the eye. We expect the immune peptide to get attention in treating eye diseases and to provide a direction for eye disease immune peptide research.
Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity
Authors: Jebbawi Fadi , Chemnitzer Alex , Dietrich Macsmeila , Pantelyushin Stanislav , Lam Juwela , Rhiner Tanya , Keller Giulia , Waldern Nina , Canonica Fabia , Fettelschoss-Gabriel Antonia
Published: July 2024

Background

Insect bite hypersensitivity (IBH) is the most frequent skin allergy of horses and is highly debilitating, especially in the chronic phase. IBH is caused by IgE-mediated hypersensitivity reactions to culicoides midge bites and an imbalanced immune response that reduces the welfare of affected horses.

Objective

In the present study, we investigated the pathological mechanisms of IBH, aiming to understand the immune cell modulation in acute allergic skin lesions of IBH horses with the goal of finding possible biomarkers for a diagnostic approach to monitor treatment success.

Methods

By qPCR, we quantified the gene expression of cytokines, chemokines, and immune receptors in skin punch biopsies of IBH with different severity levels and healthy horses simultaneously in tandem with the analysis of immune cell counts in the blood.

Results

Our data show an increase in blood eosinophils, monocytes, and basophils with a concomitant, significant increase in associated cytokine, chemokine, and immune cell receptor mRNA expression levels in the lesional skin of IBH horses. Moreover, IL-5Ra, CCR5, IFN-γ, and IL-31Ra were strongly associated with IBH severity, while IL-31 and IL-33 were rather associated with a milder form of IBH. In addition, our data show a strong correlation of basophil cell count in blood with IL-31Ra, IL-5, IL-5Ra, IFN-γ, HRH2, HRH4, CCR3, CCR5, IL-12b, IL-10, IL-1β, and CCL26 mRNA expression in skin punch biopsies of IBH horses.

Conclusion

In summary, several cytokines and chemokines have been found to be associated with disease severity, hence contributing to IBH pathology. These molecules can be used as potential biomarkers to monitor the onset and progression of the disease or even to evaluate and monitor the efficacy of new therapeutic treatments for IBH skin allergy. To our knowledge, this is the first study that investigated immune cells together with a large set of genes related to their biological function, including correlation to disease severity, in a large cohort of healthy and IBH horses.
Dissecting the mediating role of cytokines in the interaction between immune traits and sepsis: insights from comprehensive mendelian randomization
Authors: Zheng Xiangtao , Wang Yihui , Wang Yuming , Wang Xiaofeng , Pei Lei , Zhao Shanzhi , Gong Fangchen , Li Ranran , Liu Huan , Liu Wenbin , Mao Enqiang , Yang Zhitao , Chen Erzhen , Chen Ying
Published: July 2024

Background

Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.

Methods

Genetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.

Results

Our MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.

Conclusion

Our MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.
Four-year real-world experience of secukinumab in a large Italian cohort of axial spondyloarthritis
Authors: Ramonda Roberta , Lorenzin Mariagrazia , Chimenti Maria Sole , D’Angelo Salvatore , Marchesoni Antonio , Selmi Carlo , Lubrano Ennio , Santo Leonardo , Luchetti Gentiloni Michele Maria , Atzeni Fabiola , Cauli Alberto , Manara Maria , Rossini Maurizio , Foti Roberta , Cozzi Giacomo , Scagnellato Laura , Ferraioli Mario , Carriero Antonio , Luciano Nicoletta , Ruzzon Francesca , Fatica Mauro , Fracassi Elena , Doria Andrea , Foti Rosario , Carletto Antonio
Published: July 2024

Objectives

This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA).

Methods

Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded.

Results

We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex.

Conclusions

Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.
Capture and killing of small cetaceans in the Faroe Islands is inhumane and offers little scope for improvement
Authors: Simmons Alick
Published: July 2024

The capture and killing of free-living small cetaceans in the Faroe Islands is described. After being driven on-shore by motor vessels, the animals are killed without pre-stunning using officially-prescribed methods that involve severing the spinal cord and the associated blood vessels using a long-handled lance. The claim that this induces near instantaneous unconsciousness and death lacks supporting evidence: it is believed that the animals are simply paralyzed, not immediately rendered unconscious. The cervical and spinal arterial circulation of cetaceans differs from that of terrestrial mammals and it is likely the spinal lance does not completely destroy the supply of oxygenated blood to the brain. In conclusion, the entire process from driving the animals onto the shore, to restraint and to killing stranded cetaceans is very likely to be detrimental to their welfare. Detailed studies would be necessary to determine the veracity of the claimed efficacy of the process. A bespoke humane killer may improve welfare at the time of killing but its development is considered challenging.
The therapeutic potential and application of marine alkaloids in treating breast cancer
Authors: Yu Jing , Wang Xinmin , Du Peixin , Shi Hubing
Published: July 2024

Breast cancer is a major threat to women’s health worldwide. Although the 5-year survival rate is relatively high, treating recurrent and metastatic breast cancer remains challenging. Existing anticancer drugs are often accompanied by adverse reactions; thus, there is an urgent need to explore safer and more effective treatment options. Marine natural compounds, especially alkaloids, are considered to be a potential treasure trove of new anticancer drugs due to their unique chemical structure and wide range of biological activities. A variety of marine alkaloids against breast cancer, including ecteinascidins, halichondrins, manzamines, and trabectedins, have opened new avenues for breast cancer treatment by employing multiple mechanisms, such as inducing cell apoptosis and autophagy, blocking cell cycle, inhibiting angiogenesis, targeting oncogene pathways, and inhibiting metastasis and invasion. Currently, Yondelis (trabectedin) has completed phase II clinical trials in patients with breast cancer and has shown certain efficacy. However, the clinical application of marine alkaloids still needs further research and development. This article deeply explores the mechanism of action of marine alkaloids against breast cancer and anticipates their clinical application prospects. With the deepening of research and the advancement of development, marine alkaloids are expected to bring new breakthroughs in breast cancer treatment.
The influence of benzene on the composition, diversity and performance of the anodic bacterial community in glucose-fed microbial fuel cells
Authors: Tyszkiewicz Natalia , Truu Jaak , Młynarz Piotr , Pasternak Grzegorz
Published: July 2024

Bioelectrochemical systems offer unique opportunities to remove recalcitrant environmental pollutants in a net positive energy process, although it remains challenging because of the toxic character of such compounds. In this study, microbial fuel cell (MFC) technology was applied to investigate the benzene degradation process for more than 160 days, where glucose was used as a co-metabolite and a control. We have applied an inoculation strategy that led to the development of 10 individual microbial communities. The electrochemical dynamics of MFC efficiency was observed, along with their 1H NMR metabolic fingerprints and analysis of the microbial community. The highest power density of 120 mW/m2 was recorded in the final period of the experiment when benzene/glucose was used as fuel. This is the highest value reported in a benzene/co-substrate system. Metabolite analysis confirmed the full removal of benzene, while the dominance of fermentation products indicated the strong occurrence of non-electrogenic reactions. Based on 16S rRNA gene amplicon sequencing, bacterial community analysis revealed several petroleum-degrading microorganisms, electroactive species and biosurfactant producers. The dominant species were recognised as Citrobacter freundii and Arcobacter faecis. Strong, positive impact of the presence of benzene on the alpha diversity was recorded, underlining the high complexity of the bioelectrochemically supported degradation of petroleum compounds. This study reveals the importance of supporting the bioelectrochemical degradation process with auxiliary substrates and inoculation strategies that allow the communities to reach sufficient diversity to improve the power output and degradation efficiency in MFCs beyond the previously known limits. This study, for the first time, provides an outlook on the syntrophic activity of biosurfactant producers and petroleum degraders towards the efficient removal and conversion of recalcitrant hydrophobic compounds into electricity in MFCs.
Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model
Authors: Krishna Venkatramana D. , Chang Allison , Korthas Holly , Var Susanna R. , Seelig Davis M. , Low Walter C. , Li Ling , Cheeran Maxim C. -J.
Published: July 2024

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe COVID-19, and sexual dimorphism in clinical outcomes has been reported. Neurological symptoms are widely observed in COVID-19 patients, with many survivors exhibiting persistent neurological and cognitive impairment. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6J mice were intranasally inoculated with SARS-CoV-2 lineage B.1.351, a variant known to infect mice. Older male mice exhibited a significantly greater weight loss and higher viral loads in the lung at 3 days post infection. Notably, no viral RNA was detected in the brains of infected mice. Nevertheless, expression of IL-6, TNF-α, and CCL-2 in the lung and brain increased with viral infection. RNA-seq transcriptomic analysis of brains showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, implicating innate immunity, defense response to virus, and cerebrovascular and neuronal functions. These findings demonstrate that SARS-CoV-2 infection triggers a neuroinflammatory response, despite the lack of detectable virus in the brain. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and suppression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.
Carnitine O-octanoyltransferase (CROT) deficiency in mice leads to an increase of omega-3 fatty acids
Authors: Okui Takehito , Kuraoka Shiori , Iwashita Masaya , Itagawa Rei , Kasai Taku , Aikawa Masanori , Singh Sasha A. , Aikawa Elena
Published: July 2024

Introduction: Carnitine O-octanoyltransferase (CROT) is a well-established peroxisomal enzyme involved in liver fatty acid oxidation, but less is known about its recently discovered role in promoting vascular calcification, and whether CROT-dependent liver metabolism contributes to the latter. To date, CROT function in the context of calcification potential has been conducted in the dyslipidemic low-density lipoprotein receptor-deficient (Ldlr−/−) mice.

Objectives: To differentiate peroxisome and CROT-dependent lipid biology from that of lipoprotein-mediated lipid biology, we therefore conducted a metabolomic analysis of the liver and plasma of normolipidemic CROT-deficient (Crot−/−) mice.

Methods: We performed LC-MS-based metabolomics on liver and plasma derived from Crot−/− and Crot +/− mice and sibling Crot+/+ mice, using a dual-phase metabolite extraction protocol, and multiple LC-MS acquisition strategies.

Results: We identified between 79 to 453 annotated metabolites from annotated metabolites from liver samples, and 117 to 424 annotated metabolites from plasma samples. Through differential abundance analysis, we determined that omega-3 fatty acids such as EPA, DPA, and DHA were higher in the liver of Crot−/− and Crot +/− mice than Crot+/+ mice. EPA were higher in plasma of Crot−/− mice than Crot+/+ mice. We also determined that the anti-inflammatory dicarboxylic acids, tetradecanedioic acid and azelaic acid, were higher in the plasma of CROT-deficient mice.

Conclusion: Our study associated genetic CROT deletion with increased levels of anti-inflammatory molecules in mouse liver and plasma. These results suggest a potential mechanism for anti-calcification effects of CROT suppression and the potential use of omega-3 fatty acids as biomarkers for future CROT inhibition therapies.
The role of Immune cells in Alzheimer's disease: a bidirectional Mendelian randomization study
Authors: Zhang Erdong , Chen Tingting , Chen Yanqin , Long Chenxiang , Tao Ling , Shen Xiangchun , Dai Fengqiu
Published: July 2024

Background

Alzheimer's disease (AD) is a leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau proteins, leading to neuroinflammation and neuronal damage. The role of the immune system in AD pathogenesis is increasingly recognized, prompting an exploration of the causal relationship between immune cells and AD by using Mendelian randomization (MR) approaches.

Methods

Utilizing genome-wide association study (GWAS) data from European cohorts, we conducted an MR study to investigate the causal links between immune cell phenotypes and AD. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a genome-wide significance threshold and applied various MR methods, including MR Egger, Weighted median, and inverse variance weighted analysis, to assess the causality between 731 immune phenotypes and AD.

Results

Our MR analysis identified 15 immune cell types with significant causal relationships to AD pathogenesis. Notably, the absolute count of CD28−CD4−CD8− T cells and the expression of HLA DR on B cells were linked to a protective effect against AD, while 13 other immune phenotypes were identified as contributing to the risk factors for the disease. The causal effects of AD on immunophenotypic traits are predominantly negative, implying that AD may impair the functionality of immune cells. Validation through independent datasets, such as FinnGen and GCST90027158, confirmed the causal association between six specific immune cells and AD.

Conclusion

This comprehensive MR study elucidates the intricate network of causal relationships between diverse immunophenotypic traits and AD, providing novel insights into the immunopathogenesis of AD. The findings suggest potential immunological targets that could be leveraged for early diagnosis, disease monitoring, and therapeutic intervention.
Assessment of corneal nerve regeneration after axotomy in a compartmentalized microfluidic chip model with automated 3D high resolution live-imaging
Authors: Bonneau Noémie , Potey Anaïs , Blond Frédéric , Guerin Camille , Baudouin Christophe , Peyrin Jean-Michel , Brignole-Baudouin Françoise , Réaux-Le Goazigo Annabelle
Published: July 2024

Introduction

Damage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings.

Methods

To overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live–imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy.

Results

Physical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72 h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72 h of exposure (versus 34% regrowth without any compound).

Discussion

Combining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions.
Effects of nusinersen on motor function in children with spinal muscular atrophy: a retrospective study
Authors: Chen Yuyi , Yang Dongling , Huang Xuelin , Feng Juntan , Zhao Qingqing , Huang Huixian , Liang Lushi , Zhang Xinxin , Ruan Yiyan
Published: July 2024

Background

Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to evaluate the efficacy of nusinersen treatment on motor function in children with SMA.

Methods

A retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up.

Results

Of patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0–52), and the median age at initiation of treatment was 44.5 months (range 5–192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point (p = 0.173), 4.7-point (p = 0.021) and 2.7-point (p = 0.013) were observed from baseline to 14 months of follow-up for the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores (r = −0.567, p = 0.043; r = −0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores (r = −0.714, p = 0.014; r = −0.638 and p = 0.035, respectively).

Conclusion

Our study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.
Case report: When infection lurks behind malignancy: a unique case of primary bone lymphoma mimicking infectious process in the spine
Authors: Jaafari Ayoub , Rizzo Ornella , Mansour Sohaïb , Chbabou Anas , Trepant Anne-Laure , Attou Rachid , Mathey Celine
Published: July 2024

Primary bone lymphoma of the spine (PBL) is a rare entity that may be misdiagnosed due to its atypical location and clinical and imaging features mimicking certain pathologies as infectious processes, which complicates and delays diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed inflammatory syndrome, and an image of spondylodiscitis of the lumbar spine associated with a morphological and metabolical widespread invasion posteriorly suggesting epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation, while morphological and metabolic findings can be alike.
Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet
Authors: Harvei Silje , Skogen Vemund , Egelandsdal Bjørg , Birkeland Signe , Paulsen Jan Erik , Carlsen Harald
Published: July 2024

Introduction

Lipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named “metabolic endotoxemia.” This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet.

Methods

We supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16–17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay.

Results and discussion

Our results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.
Increasing the frequency of plant-based food intake in daily diets reduces the risk of cardiovascular disease among elderly Chinese: a cohort study
Authors: Hou Xin-Zheng , Wu Qian , Lv Qian-Yu , Yang Ying-Tian , Li Lan-Lan , Ye Xue-Jiao , Yang Chen-Yan , Lv Yan-Fei , Wang Shi-Han
Published: July 2024

Objective

There is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption.

Methods

This study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011–2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results.

Results

This study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise.

Conclusion

The PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.
Case report: 18F-FDG PET/CT skeletal superscan-like in an adult patient with acute lymphoblastic leukemia
Authors: Hu Yu , Dai Wenli , Wang Peng , Feng Yawen , Feng Hui , Li Jun
Published: July 2024

We herein describe a rare case of adult acute lymphoblastic leukemia with an 18florine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) skeletal superscan-like appearance. The degree of bone marrow uptake was so intense that it far exceeded the level of physiological cerebral uptake and radiourinary activity. The distribution was remarkably similar to a superscan seen on skeletal scintigraphy. Skeletal superscans of 18F-FDG PET/CT have been reported in hematological diseases, solid tumors with extensive bone metastasis, and metabolic diseases. Thus, we reviewed the PET/CT images of cases reported, indicating that more homogeneous distribution, without primary tumor and specific mandibular and skull activity, may be suggestive of hematological diseases.
Growing teratoma syndrome of the ovary: a case report and literature review
Authors: Tao Jiaying , Shi Zhixian , Li Mulan , Li Tingting
Published: July 2024

Growing teratoma syndrome (GTS) is a rare condition that arises secondary to malignant germ cell tumors. It is characterized by an enlarging abdominal mass during or after chemotherapy, normal tumor markers, and histopathological indications of mature teratoma components. Awareness of GTS is limited, and it is often mistaken for disease progression or recurrence. This misdiagnosis can lead to delayed treatment and increased risk of complications. Therefore, early identification of GTS is crucial to avoid unnecessary systemic treatments and reduce financial burden. GTS is unresponsive to chemotherapy or radiotherapy and complete surgical resection is the sole therapeutic strategy. In this report, we present a case of GTS in a 20-year-old female following treatment for immature teratoma, alongside a review of the relevant literature aimed at enriching our insight into the clinical manifestations of GTS.
A new method for assessing tibial torsion using computerized tomography in a pediatric population
Authors: Gavira Nathaly , Cochard Blaise , Guanziroli Nastassia , Di Laura Frattura Giorgio , Dayer Romain , Ceroni Dimitri
Published: July 2024

Purpose

Tibial torsion disorders may lead to abnormal gait, frequently leading to a consultation with a pediatric orthopedic surgeon. The present study evaluated an alternative method for assessing tibial torsion on computerized tomography (CT) images that considers the tibial distal axis to be equivalent to the geometric axis of the tibiotalar joint.

Methods

One hundred CT scans were reviewed retrospectively, and four measurements were taken: proximal transtibial angle (PTTA), posterior margin tibial plateau angle (PMTPA), intermalleolar angle (IMA), and talar angle (TA). The tibial torsion angle was then calculated using these different angles.

Results

The patient cohort comprised 38 girls and 62 boys, with a mean age of 12 ± 4.4 years. Median PTTA and PMTPA were −8.4° ± 14.7° and −8.8° ± 14.2°, respectively, with no statistically significant difference. Mean IMA and TA were 23° ± 16.2° and 17.2° ± 16.9°, respectively, with a statistically significant difference. Mean total measurement time per patient was 6'44", with means of 2'24" for PTTA, 36" for PMTPA, 2'14" for IMA, and 1'12" for TA.

Conclusion

Tibial torsion values may differ significantly depending on the axis chosen to define tibial orientation. At the level of the proximal tibia, the choice of PTTA or PMTPA had little influence on the calculation of the tibial torsion angle. There was a significant difference of 5.8° when measuring the distal tibia. Measuring the PMTPA and TA is probably more suited for use in clinical practice because their tracing is simple and faster.
Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review
Authors: Lages Lívio Portela de Deus , Bergamaschi Cristiane de Cássia , Lopes Luciane Cruz , da Frota Eduardo Gomes , Silva Marcus Tolentino , Monte Thiago Lima , Motta Rogério Heládio Lopes
Published: July 2024

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries.

Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out.

Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo.

Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.
Effects of Alhagi maurorum Medik polysaccharide derived from different regions on the intestinal immune functions of lambs
Authors: Manafu Zulikeyan , Du Ronglijiao , Malajiang Xieraili , Abulikemu Gulimire , Xue Lijun , Bierdelieke Ayibike , Xie Yuan , Liu Dandan , Mai Zhanhai , Guo Qingyong , Wusiman Adelijiang , Li Bin , Abula Saifuding
Published: July 2024

Introduction: Plant polysaccharide are widely studied as potential prebiotics because of their potential to protect and enhance the immunity of lambs.

Methods: In this study, the polysaccharide content of Alhagi maurorum Medik from Aksu (AK) and Shanshan (SS) at different cutting periods was determined, and the functions of Alhagi maurorum Medik polysaccharide were investigated to useas an immunomodulator.

Results: Our results indicated that the content of Alhagi maurorum Medik polysaccharide is the highest at the maturity stage, and the polysaccharide content of Alhagi maurorum Medik produced in Shanshan area is higher as compared to the Aksu area. The serum IgG, duodenum IgA, TNF-α, IL-4, IL-10 contents, jejunum IgA, TNF-α, IL-4, IL-17 contents, ileum IgA, IL-17 contents, duodenum villus height, crypt depth and jejunum crypt depth of lambs were significantly adjusted in the SS group as compared to CK control group and AK groups (p < 0.05). Furthemore, the sequencing results showed that SS polysaccharide promoted the release of large amounts of IgA and enhanced the immunal function of intestine by regulating the IgA production pathway and B-cell receptor signaling to activate B cells in the T-dependent pathway.

Discussion: Altogether, Alhagi maurorum Medik polysaccharide from SS group holds a promising potential to be used as a valuable immunopotentiator for optimizing the immune system of intestine in lambs.
A novel approach to brain tumor detection using K-Means++, SGLDM, ResNet50, and synthetic data augmentation
Authors: Sarah Ponuku , Krishnapriya Srigiri , Saladi Saritha , Karuna Yepuganti , Bavirisetti Durga Prasad
Published: July 2024

Introduction: Brain tumors are abnormal cell growths in the brain, posing significant treatment challenges. Accurate early detection using non-invasive methods is crucial for effective treatment. This research focuses on improving the early detection of brain tumors in MRI images through advanced deep-learning techniques. The primary goal is to identify the most effective deep-learning model for classifying brain tumors from MRI data, enhancing diagnostic accuracy and reliability.

Methods: The proposed method for brain tumor classification integrates segmentation using K-means++, feature extraction from the Spatial Gray Level Dependence Matrix (SGLDM), and classification with ResNet50, along with synthetic data augmentation to enhance model robustness. Segmentation isolates tumor regions, while SGLDM captures critical texture information. The ResNet50 model then classifies the tumors accurately. To further improve the interpretability of the classification results, Grad-CAM is employed, providing visual explanations by highlighting influential regions in the MRI images.

Result: In terms of accuracy, sensitivity, and specificity, the evaluation on the Br35H::BrainTumorDetection2020 dataset showed superior performance of the suggested method compared to existing state-of-the-art approaches. This indicates its effectiveness in achieving higher precision in identifying and classifying brain tumors from MRI data, showcasing advancements in diagnostic reliability and efficacy.

Discussion: The superior performance of the suggested method indicates its robustness in accurately classifying brain tumors from MRI images, achieving higher accuracy, sensitivity, and specificity compared to existing methods. The method's enhanced sensitivity ensures a greater detection rate of true positive cases, while its improved specificity reduces false positives, thereby optimizing clinical decision-making and patient care in neuro-oncology.
A simple and effective deep neural network based QRS complex detection method on ECG signal
Authors: Zhao Wei , Li Zhenqi , Hu Jing , Ma Yunju
Published: July 2024

Introduction: The QRS complex is the most prominent waveform within the electrocardiograph (ECG) signal. The accurate detection of the QRS complex is an essential step in the ECG analysis algorithm, which can provide fundamental information for the monitoring and diagnosis of the cardiovascular diseases.

Methods: Seven public ECG datasets were used in the experiments. A simple and effective QRS complex detection algorithm based on the deep neural network (DNN) was proposed. The DNN model was composed of two parts: a feature pyramid network (FPN) based backbone with dual input channels to generate the feature maps, and a location head to predict the probability of point belonging to the QRS complex. The depthwise convolution was applied to reduce the parameters of the DNN model. Furthermore, a novel training strategy was developed. The target of the DNN model was generated by using the points within 75 milliseconds and beyond 150 milliseconds from the closest annotated QRS complexes, and artificial simulated ECG segments with high heart rates were generated in the data augmentation. The number of parameters and floating point operations (FLOPs) of our model was 26976 and 9.90M, respectively.

Results: The proposed method was evaluated through a cross-dataset test and compared with the sophisticated state-of-the-art methods. On the MITBIH NST, the proposed method demonstrated slightly better sensitivity (95.59% vs. 95.55%) and lower presicion (91.03% vs. 92.93%). On the CPSC 2019, the proposed method have similar sensitivity (95.15% vs.95.13%) and better precision (91.75% vs. 82.03%).

Discussion: Experimental results show the proposed algorithm achieved a comparable performance with only a few parameters and FLOPs, which would be useful for the application of ECG analysis on the wearable device.
Oxidative stress and plasma ceramides in broiler chickens
Authors: Klandorf Hillar , Dartigue Vincent
Published: July 2024

The selection for rapid growth in chickens has rendered meat-type (broiler) chickens susceptible to develop metabolic syndrome and thus inflammation. The sphingolipid ceramide has been linked as a marker of oxidative stress in mammals, however, the relationship between sphingolipid ceramide supply and oxidative stress in broiler chickens has not been investigated. Therefore, we employed a lipidomic approach to investigate the changes in circulating sphingolipid ceramides in context of allopurinol-induced oxidative stress in birds. Day zero hatched chicks (n = 60) were equally divided into six groups; an unsupplemented control, an allopurinol group (25 mg/kg body weight), a conjugated linoleic acid (CLA) group where half of the oil used in the control diet was substituted for a CLA oil mixture, a CLA and an allopurinol group utilizing the same dose of CLA and allopurinol, a berberine (BRB) group consisting of berberine supplementation (200 mg/kg feed), and a BRB and allopurinol group, utilizing the same dose of BRB and allopurinol. Conjugated linoleic acid and berberine were utilized to potentially enhance antioxidant activity and suppress the oxidative stress induced by allopurinol treatment. Body weight, plasma uric acid, nonesterified fatty acids (NEFA) and sphingolipid ceramides were quantified. Allopurinol induced an inflammatory state as measured by a significant reduction in plasma uric acid - an antioxidant in birds as well as a metabolic waste product. Results showed that both total and saturated sphingolipid ceramides declined (p < 0.05) with age in unsupplemented chicks, although plasma ceramides C16:0 and 18:0 increased in concentration over the study period. Simple total and saturated sphingolipid ceremide’s were further decreased (p < 0.05) with allopurinol supplementation, however, this may be an indirect consequence of inducing an inflammatory state. Neither CLA or BRB were able to significantly attenuate the decline. The administration of allopurinol specifically targets the liver which in birds, is the primary organ for fatty acids synthesis. For this reason, sphingolipid ceramide production might have been unwittingly affected by the addition of allopurinol.