bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain
Authors: Ohm Melanie , Hosseini Shirin , Lonnemann Niklas , He Wei , More Tushar , Goldmann Oliver , Medina Eva , Hiller Karsten , Korte Martin 
Published: August 2024

AbstractDespite advances in antimicrobial and anti-inflammatory treatment, inflammation and its consequences remain a major challenge in the field of medicine. Inflammatory reactions can lead to life-threatening conditions such as septic shock, while chronic inflammation has the potential to worsen the condition of body tissues and ultimately lead to significant impairment of their functionality. Although the central nervous system has long been considered immune privileged to peripheral immune responses, recent research has shown that strong immune responses in the periphery also affect the brain, leading to reactive microglia, which belong to the innate immune system and reside in the brain, and neuroinflammation. The inflammatory response is primarily a protective mechanism to defend against pathogens and tissue damage. However, excessive and chronic inflammation can have negative effects on neuronal structure and function. Neuroinflammation underlies the pathogenesis of many neurological and neurodegenerative diseases and can accelerate their progression. Consequently, targeting inflammatory signaling pathways offers potential therapeutic strategies for various neuropathological conditions, particularly Parkinson’s and Alzheimer’s disease, by curbing inflammation. Here the blood–brain barrier is a major hurdle for potential therapeutic strategies, therefore it would be highly advantageous to foster and utilize brain innate anti-inflammatory mechanisms. The tricarboxylic acid cycle-derived metabolite itaconate is highly upregulated in activated macrophages and has been shown to act as an immunomodulator with anti-inflammatory and antimicrobial functions. Mesaconate, an isomer of itaconate, similarly reduces the inflammatory response in macrophages. Nevertheless, most studies have focused on its esterified forms and its peripheral effects, while its influence on the CNS remained largely unexplored. Therefore, this study investigated the immunomodulatory and therapeutic potential of endogenously synthesized itaconate and its isomer mesaconate in lipopolysaccharide (LPS)-induced neuroinflammatory processes. Our results show that both itaconate and mesaconate reduce LPS-induced neuroinflammation, as evidenced by lower levels of inflammatory mediators, reduced microglial reactivity and a rescue of synaptic plasticity, the cellular correlate of learning and memory processes in the brain. Overall, this study emphasizes that both itaconate and mesaconate have therapeutic potential for neuroinflammatory processes in the brain and are of remarkable importance due to their endogenous origin and production, which usually leads to high tolerance.
Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance
Authors: Sun Yitian , Li Qinyi , Huang Yufei , Yang Zijing , Li Guohua , Sun Xiaoyu , Gu Xiaoqing , Qiao Yunhao , Wu Qibiao , Xie Tian , Sui Xinbing 
Published: August 2024

AbstractRedox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future.
Graphical Abstract
Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation
Authors: Yuan Shyng-Shiou F. , Chan Leong-Perng , Nguyen Hieu D. H. , Su Chang-Wei , Chen Yuk-Kwan , Chen Jeff Yi-Fu , Shimodaira Shigetaka , Hu Stephen Chu‐Sung , Lo Steven , Wang Yen-Yun 
Published: August 2024

Abstract
Background
Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive.

Methods
Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE.

Results
We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters.

Conclusion
Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.
A scalable, chromatography-free, biocatalytic method to produce the xyloglucan heptasaccharide XXXG
Authors: Rodd Andrew M. , Mawhinney William M. , Brumer Harry 
Published: August 2024

AbstractXyloglucan oligosaccharides (XyGOs) are highly branched, complex carbohydrates with a variety of chemical and biotechnological applications. Due to the regular repeating pattern of sidechain substitution of the xyloglucan backbone, well-defined XyGOs are readily accessed for analytical and preparative purposes by specific hydrolysis of the polysaccharide with endo-glucanases. To broaden the application potential of XyGOs, we present here an optimized, scalable method to access large quantities of galactosylated XyGOs by treatment of the bulk agricultural by-product, tamarind kernel powder (TKP), with a highly specific endo-xyloglucanase at high-solids content. Subsequent β-galactosidase treatment reduced XyGO complexity to produce exclusively the branched heptasaccharide XXXG (Xyl3Glc4: [α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-[α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-[α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-D-Glcp). The challenge of removing the co-product galactose was overcome by fermentation with baker’s yeast, thereby avoiding chromatography and other fractionation steps to yield highly pure XXXG. This simplified approach employs many of the core concepts of green chemistry and engineering, enables facile production of 100 g quantities of XyGOs and XXXG for laboratory use, and serves as a guide to further production scale-up for applications, including as prebiotics, plant growth effectors and elicitors, and building blocks for glycoconjugate synthesis.
Anti-neuroinflammatory effects of the KIOM -patented Polygonum multiflorum maximized root tuber against LPS-stimulated BV2 Cells
Authors: Oh Tae Woo , Ban Yeongjun , Kang Youngmin 
Published: August 2024

AbstractThe main pathological mechanism of neurodegeneration is neuroinflammation. It is known that the persistent neuroinflammatory response is harmful by causing secondary nerve tissue damage. Meanwhile, P. multiflorum is a traditional oriental medicinal herb. It has been used as a hematopoietic agent and is used to treat a variety of diseases and conditions. The aim of the present study was to compare the anti-inflammatory efficacy between the commonly available P. multiflorum (C1) and the KIOM-patented in vitro-propagated P. multiflorum (K1), which had higher content of active ingredients and biomass, using culture and cultivation conditions of LPS-induced neuroinflammation. After stimulation with LPS and treatment with C1 and K1 in mouse microglial BV-2 cells, nitric oxide (NO) production, pro-inflammatory cytokine secretion, inducible NO synthase (iNOS) expression, MAPK phosphorylation and transcription factor activity were assessed. We examined the antioxidant effect using DPPH and production of nitric oxide (NO). C1 and K1 suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. Furthermore, we determined the levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms. Additionally, C1 and K1 also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. In all experimental results, excellent anti-neuroinflammatory effects were confirmed at a lower dose in K1 than in C1, which is believed to be due to the increased biomass. Therefore, K1 is expected to be more effective than C1 and can be applied more broadly in the development of prevention and treatment of various inflammatory-mediated neurodegenerative diseases.
A risk prediction model for unexplained early neurological deterioration following intravenous thrombolysis
Authors: Zhu Bifeng , Wang Dan , Zuo Jing , Huang Yi , Gao Chang , Jiang Haiwei , Yan Dan 
Published: August 2024

Abstract
Background and objectives
Early neurological deterioration (END) post-intravenous thrombolysis significantly impacts the long-term prognosis of stroke patients. This study aimed to establish a rapid risk prediction model for unexplained END following intravenous thrombolysis.

Methods
This prospective study consecutively enrolled patients with acute ischemic stroke treated with recombinant tissue plasminogen activator intravenous thrombolysis at the Department of Neurology, Third People’s Hospital of Hubei Province, and Yangluo Hospital District between June 2019 and December 2022. Unexplained END was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score between admission and 24 h. A nomogram was developed and assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). The calibration was assessed using the Hosmer–Lemeshow test.

Results
A total of 211 patients (130 males and 110 patients aged < 65 years) were included, with 66 experiencing unexplained END. Multivariate logistic regression analysis identified large arterial disease, transient ischemic attack, high blood glucose, high neutrophil/lymphocyte ratio, important perforator disease, and low the Alberta Stroke Program Early CT scores (APSECTS) as independent risk factors for END and established the nomogram used above indicators. The nomogram showed an AUC-ROC of 0.809 (95% CI 0.7429–0.8751), with a specificity of 0.862 and sensitivity of 0.712. The positive predictive value was 0.702, and the negative predictive value was 0.868. The Hosmer–Lemeshow goodness-of-fit test (χ2 = 1.069, P = 0.169) indicated acceptable model calibration.

Conclusion
This study successfully established a risk prediction model for END following intravenous thrombolysis and the model demonstrates good stability and predictive capacity. Further validation through a prospective, multicenter study is necessary.
Computational analysis of non-synonymous SNPs in the human LCN2 gene
Authors: Sivakumar Kaniha , Subbiah Usha 
Published: August 2024

Abstract
Background
Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism in the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, and colorectal and pancreatic cancer. Identifying deleterious functional non-synonymous SNPs in the LCN2 gene is crucial in understanding how these genetic variations affect its structure and function.

Methods
Several in silico tools such as SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, and SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, and NetsurfP-2.0, secondary structure of the protein by SOPMA and PSIPRED, while its interaction with other genes and proteins was analyzed using GeneMANIA and STRING, respectively, and AlphaFold for protein's 3D structure prediction.

Results
The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) and their structure and function were analyzed using prediction tools. I-MUTANT 2.0 predicted an increase in stability with the nsSNPs rs139418967, while the other shows decrease in protein stability with the 6 nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) which was validated using MUpro. ConSurf identified the 6 high-risk nsSNPs to be in the conserved regions of the protein. The result showed that rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, and rs368926734 were found to be highly conserved and the variant amino acids. According to NetsurfP-2.0 server, the result showed that rs11556770 (Q39H), rs139418967 (L6P), rs368926734 (Y135H) were predicted to be exposed and rs142623708 (M71I), rs200107414 (Y52C), rs368926734 (Y135) were buried. The PSIPRED server analysis indicated that the predominant secondary structure was a strand, with lesser occurrences of coil and helix.

Conclusion
Overall, the study identified detrimental nsSNPs of LCN2 using computational analysis which could be used for large population-based investigations and diagnosis.
Expert psychiatric reports for the Parole Board for England and Wales
Authors: Middleton Laura , Daly Lynne , Nathan Rajan 
Published: August 2024

SUMMARYThe Parole Board for England and Wales advises on the release, recall and licence conditions of a small subgroup of prisoners serving determinate sentences and the majority of those serving indeterminate sentences. Since the establishment of the Parole Board in 1968, the parole process has been shaped and clarified by further legislation and case law. In certain scenarios, psychiatric expert evidence may be sought to inform the Board's determination of whether a prisoner can be safely released into the community. Psychiatrists preparing expert reports for the Parole Board should be familiar with the current operationalisation of parole. This involves an understanding not only of the functioning of the Parole Board, but also of the criminal justice context in which prisoners subject to parole are managed. Having set the scene, by describing the role of the Parole Board and the wider context, this article examines how to undertake assessments and complete psychiatric reports for the Board.
Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022
Authors: Tseretopoulou Xanthippi , Ali Salma R , Bryce Jillian , Amin Nadia , Atapattu Navoda , Bachega Tania A S S , Baronio Federico , Ortolano Rita , Birkebaek Niels H , Bonfig Walter , Cools Martine , Davies Justin H , Thomas Tessy , de Vries Liat , Elsedfy Heba , Amr Nermine H , Flueck Christa E , Globa Evgenia , Guran Tulay , Yavas-Abali Zehra , Guven Ayla , Hannema Sabine E , Iotova Violeta , Konrad Daniel , Lenherr-Taube Nina , Krone Nils P , Leka-Emiri Sofia , Vlachopapadopoulou Elpis , Lichiardopol Corina , Marginean Otilia , Markosyan Renata , Neumann Uta , Niedziela Marek , Banaszak-Ziemska Magdalena , Phan-Hug Franziska , Poyrazoglu Sukran , Probst-Scheidegger Ursina , Randell Tabitha , Russo Gianni , Salerno Mariacarolina , Seneviratne Sumudu , Shnorhavorian Margarett , Thankamony Ajay , Tadokoro-Curraro Rieko , van den Akker Erica , van Eck Judith , Vieites Ana , Wasniewska Malgorzata , Ahmed S Faisal 
Published: August 2024

Abstract

Background
It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events.

Aim
Study temporal trends of AI related AE in the I-CAH Registry.

Methods
In 2022, data on the occurrence of AI-related AE in children aged &lt;18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019.

Results
In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02).

Conclusion
The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.
Frameless Stereotactic Biopsy of Brainstem Tumors Using the Stealth Autoguide: A Technical Note
Authors: Patel Ajay , Hux Nicholas , Virtanen Piiamaria S. , Budnick Hailey , Kazi Fezaan , Tailor Jignesh K. 
Published: August 2024

BACKGROUND AND OBJECTIVES:
In the molecular era of neuro-oncology, it is increasingly necessary to obtain tissue for next-generation sequencing and methylome profile for prognosis and targeted oncological management. Brainstem tumors can be technically challenging to biopsy in the pediatric population. Frame-based and frameless techniques have previously been described and proven to be safe and efficacious in children. Recent cranial robotic guidance platforms have augmented the fluency of frameless stereotactic approaches, but the technical nuances of these procedures in children are not often discussed. We present a technical workflow for frameless stereotactic biopsy of brainstem tumors in children using the Medtronic Stealth Autoguide cranial robotic guidance platform and examine safety and efficacy of this surgical approach.

METHODS:
A minimally invasive, frameless, transcerebellar approach is described, including operative steps and workflow. We assessed operative times, diagnostic accuracy and yield, and complication rates.

RESULTS:
Five patients underwent biopsy with the technique described. The youngest patient in our series was of 2 years. The intended target was achieved on postoperative imaging in all cases, and diagnostic tissue was obtained in all 5 patients. One patient had a clinically insignificant hemorrhage.

CONCLUSION:
Frameless stereotactic biopsy of the brainstem can be performed safely, efficiently, and accurately using the Medtronic Stealth Autoguide robotic platform in children as young as 2 years.
Absence of Foramen Spinosum on Computed Tomography Scan Determines Feasibility of Middle Meningeal Artery Embolization
Authors: Hubbard Zachary S. , Cunningham Conor M. , Porto Guilherme , Sowlat Mohammad-Mahdi , Elawady Sameh Samir , Al Kasab Sami , Kicielinski Kimberly , Lena Jonathan , Spiotta Alejandro M. 
Published: August 2024

BACKGROUND AND OBJECTIVES:
Middle meningeal artery embolization (MMAE) has emerged as a novel treatment of chronic subdural hematoma. In 0.5% of patients, however, there exists an ophthalmic origin of the middle meningeal artery (MMA) known as the recurrent meningeal artery. It is known that the recurrent MMA is associated with failure of its skeletal aperture, the foramen spinosum, to form during development. The aim of this study was to investigate MMAE feasibility as a function of the presence/absence of the foramen spinosum on preprocedure computed tomography (CT) scan.

METHODS:
We performed a retrospective review of 100 consecutive patients undergoing MMAE from January 2022 to December 2023 at the Medical University of South Carolina. Preprocedure CT scan of the head was reviewed, and the presence or absence of the foramen spinosum, along with laterality, was recorded. Subsequently, angiographic studies were reviewed.

RESULTS:
All patients (n = 100) had preprocedural CT scan available for review. The incidence of an absent foramen spinosum was 3% (n = 3). All absent foramen spinosum were left sided (2F, 1M). All embolization attempts in these patients were aborted due to recurrent meningeal artery. 97% of patients had patent bilateral foramen spinosum (n = 97). Two of these patients possessed partial ophthalmic contribution to the MMA (2%), and embolization was not performed. In patients with patent foramen spinosum, successful embolization was achieved in 92/97 patients (94.8%).

CONCLUSION:
The review of preprocedure CT scan may serve as an opportunity to identify patients with ophthalmic arterial origin of the MMA, subverting unnecessary risks associated with catheter angiography.