bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico Modeling of Fabry Disease Pathophysiology for the Identification of Early Cellular Damage Biomarker Candidates
Authors: Gervas-Arruga Javier , Barba-Romero Miguel Ángel , Fernández-Martín Jorge Julián , Gómez-Cerezo Jorge Francisco , Segú-Vergés Cristina , Ronzoni Giacomo , Cebolla Jorge J.
Published: September 2024

Fabry disease (FD) is an X-linked lysosomal disease whose ultimate consequences are the accumulation of sphingolipids and subsequent inflammatory events, mainly at the endothelial level. The outcomes include different nervous system manifestations as well as multiple organ damage. Despite the availability of known biomarkers, early detection of FD remains a medical need. This study aimed to develop an in silico model based on machine learning to identify candidate vascular and nervous system proteins for early FD damage detection at the cellular level. A combined systems biology and machine learning approach was carried out considering molecular characteristics of FD to create a computational model of vascular and nervous system disease. A data science strategy was applied to identify risk classifiers by using 10 K-fold cross-validation. Further biological and clinical criteria were used to prioritize the most promising candidates, resulting in the identification of 36 biomarker candidates with classifier abilities, which are easily measurable in body fluids. Among them, we propose four candidates, CAMK2A, ILK, LMNA, and KHSRP, which have high classification capabilities according to our models (cross-validated accuracy ≥ 90%) and are related to the vascular and nervous systems. These biomarkers show promise as high-risk cellular and tissue damage indicators that are potentially applicable in clinical settings, although in vivo validation is still needed.
Biologic Brachytherapy: Genetically Modified Surgical Flap as a Therapeutic Tool—A Systematic Review of Animal Studies
Authors: Pascal Wiktor , Gotowiec Mateusz , Smoliński Antoni , Suchecki Michał , Kopka Michał , Pascal Adriana , Włodarski Paweł
Published: September 2024

Surgical flaps are rudimentary tools in reconstructive surgery, especially following extensive solid tumour resections. They cover skin and soft tissue defects but are prone to ischaemia and necrosis. Since their primary aim is reconstruction, they rarely exhibit a therapeutic activity against the treated disease. Attempts have been made to develop a new therapeutic strategy—biologic brachytherapy, which uses genetically engineered surgical flaps as a drug delivery vehicle, allowing the flap tissue to act as a “biologic pump”. This systematic review summarizes the preclinical evidence on using genetically modified surgical flaps. A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science. The initial literature search yielded 714 papers, and, eventually, seventy-seven studies were included in qualitative analysis. The results show that genetic enhancement of flaps has been used as a local or systemic therapy for numerous disease models. Frequently, it has been used to increase flap survival and limit ischaemia or promote flap survival in a non-ischemic context, with some studies focusing on optimizing the technique of such gene therapy. The results show that genetically modified flaps can be successfully used in a variety of contexts, but we need more studies to implement this research into specific clinical scenarios.
Two Half-Size ATP-Binding Cassette Transporters Are Implicated in Aluminum Tolerance in Soybean
Authors: Huang Junjun , Li Huanan , Chen Yiwei , Li Xiaoyu , Jia Ziyu , Cheng Kunxia , Wang Luyu , Wang Huahua
Published: September 2024

Aluminum (Al) toxicity severely restricts plant production in acidic soils. ATP-binding cassette (ABC) transporters participate in plant tolerance to various environmental stresses. However, ABC transporters implicated in soybean Al tolerance are still rare. Here, we functionally characterized two half-size ABC transporters (GmABCB48 and GmABCB52) in soybean. Expression analysis showed that GmABCB48 and GmABCB52 were induced only in the roots, especially in the root tips. Both GmABCB48 and GmABCB52 were localized at the plasma membrane. Overexpression of GmABCB48 or GmABCB52 in Arabidopsis reduced Al accumulation in roots and enhanced Al tolerance. However, expression of GmABCB48 or GmABCB52 in yeast cells did not affect Al uptake. Furthermore, transgenic lines expressing GmABCB48 or GmABCB52 had lower Al content in root cell walls than wild-type plants under Al stress. Further investigation showed that the Al content in cell wall fractions (pectin and hemicellulose 1) of transgenic lines was significantly lower than that of wild-type plants, which was coincident with the changes of pectin and hemicellulose 1 content under Al exposure. These results indicate that GmABCB48 and GmABCB52 confer Al tolerance by regulating the cell wall polysaccharides metabolism to reduce Al accumulation in roots.
Wheat Transcription Factor TaMYB60 Modulates Cuticular Wax Biosynthesis by Activating TaFATB and TaCER1 Expression
Authors: Wang Xiaoyu , Chen Wanzhen , Zhi Pengfei , Chang Cheng
Published: September 2024

Cuticular wax mixtures cover the epidermis of land plants and shield plant tissues from abiotic and biotic stresses. Although cuticular wax-associated traits are employed to improve the production of bread wheat, regulatory mechanisms underlying wheat cuticular wax biosynthesis remain poorly understood. In this research, partially redundant transcription factors TaMYB60-1 and TaMYB60-2 were identified as positive regulators of wheat cuticular wax biosynthesis. Knock-down of wheat TaMYB60-1 and TaMYB60-2 genes by virus-induced gene silencing resulted in attenuated wax accumulation and enhanced cuticle permeability. The roles of wheat fatty acyl-ACP thioesterase genes TaFATB1 and TaFATB2 in cuticular wax biosynthesis were characterized. Silencing wheat TaFATB1 and TaFATB2 genes led to reduced wax accumulation and increased cuticle permeability, suggesting that TaFATB1 and TaFATB2 genes positively contribute to wheat cuticular wax biosynthesis. Importantly, transcription factors TaMYB60-1 and TaMYB60-2 exhibit transcriptional activation ability and could stimulate the expression of wax biosynthesis genes TaFATB1, TaFATB2, and ECERIFERUM 1 (TaCER1). These findings support that transcription factor TaMYB60 positively regulates wheat cuticular wax biosynthesis probably by activating transcription of TaFATB1, TaFATB2, and TaCER1 genes.
A Novel Murine Model Enabling rAAV8-PC Gene Therapy for Severe Protein C Deficiency
Authors: Levy-Mendelovich Sarina , Avishai Einat , Samelson-Jones Benjamin J. , Dardik Rima , Brutman-Barazani Tami , Nisgav Yael , Livnat Tami , Kenet Gili
Published: September 2024

Severe protein C deficiency (SPCD) is a rare inherited thrombotic disease associated with high morbidity and mortality. In the current study, we established a viable murine model of SPCD, enabling preclinical gene therapy studies. By creating SPCD mice with severe hemophilia A (PROC−/−/F8−), the multi-month survival of SPCD mice enabled the exploration of recombinant adeno-associated viral vector-PC (rAAV8-PC) gene therapy (GT). rAAV8- PC (1012 vg/kg of AAV8-PC) was injected via the tail vein into 6–8-week-old PROC−/−/F8- mice. Their plasma PC antigen levels (median of 714 ng/mL, range 166–2488 ng/mL) and activity (303.5 ± 59%) significantly increased to the normal range after GT compared to untreated control animals. PC’s presence in the liver after GT was also confirmed by immunofluorescence staining. Our translational research results provide the first proof of concept that an infusion of rAAV8-PC increases PC antigen and activity in mice and may contribute to future GT in SPCD. Further basic research of SPCD mice with prolonged survival due to the rebalancing of this disorder using severe hemophilia A may provide essential data regarding PC’s contribution to specific tissues’ development, local PC generation, and its regulation in inflammatory conditions.
Identification of Cold Tolerance Transcriptional Regulatory Genes in Seedlings of Medicago sativa L. and Medicago falcata L.
Authors: Wang Qi , Wu Jianzhong , Di Guili , Zhao Qian , Gao Chao , Zhang Dongmei , Wang Jianli , Shen Zhongbao , Han Weibo
Published: September 2024

Alfalfa species Medicago sativa L. (MS) and Medicago falcata L. (MF), globally prominent perennial leguminous forages, hold substantial economic value. However, our comprehension of the molecular mechanisms governing their resistance to cold stress remains limited. To address this knowledge gap, we scrutinized and compared MS and MF cold-stress responses at the molecular level following 24 h and 120 h low-temperature exposure (4 °C). Our study revealed that MF had superior physiological resilience to cold stress compared with MS, and its morphology was healthier under cold stress, and its malondialdehyde content and superoxide dismutase activity increased, first, and then decreased, while the soluble sugar content continued to accumulate. Transcriptome analysis showed that after 120 h of exposure, there were different gene-expression patterns between MS and MF, including 1274 and 2983 genes that were continuously up-regulated, respectively, and a total of 923 genes were included, including star cold-resistant genes such as ICE1 and SIP1. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed numerous inter-species differences in sustained cold-stress responses. Notably, MS-exclusive genes included a single transcription factor (TF) gene and several genes associated with a single DNA repair-related pathway, whereas MF-exclusive genes comprised nine TF genes and genes associated with 14 pathways. Both species exhibited high-level expression of genes encoding TFs belonging to AP2-EREBP, ARR-B, and bHLH TF families, indicating their potential roles in sustaining cold resistance in alfalfa-related species. These findings provide insights into the molecular mechanisms governing cold-stress responses in MS and MF, which could inform breeding programs aimed at enhancing cold-stress resistance in alfalfa cultivars.
Hypothermically Stored Amnion Is Robust and Provides a Scaffold for Supporting Wound Healing by Retaining the Characteristics of Native Tissue
Authors: Harmon Katrina A. , Kimmerling Kelly A. , Avery Justin T. , Mowry Katie C.
Published: September 2024

Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), viable cells, and key proteins. To evaluate its utility, we characterized the HSAM and compared it to a native unprocessed amniotic membrane (uAM) and a dehydrated amniotic membrane (dAM), as well as assessing the functionality of the HSAM as a scaffold to promote cell growth. The HSAM, uAM, and dAM were compared using scanning electron microscopy (SEM), histology, and thickness. Scaffold durability was assessed in vitro using mechanical testing and a simulated wound fluid (SWF) model. The ability of the HSAM to act as a scaffold was evaluated using an in vitro attachment model. The HSAM showed similar structural characteristics compared to the uAM; however, the dAM was significantly more compact. There were no significant differences between the HSAM and the uAM following degradation in an SWF model. ECM- and placental-related proteins were shared between the HSAM and uAM, and the HSAM enhanced the attachment and proliferation of fibroblasts in vitro. The HSAM is substantially similar to the uAM by retaining key regulatory proteins, resisting degradation in SWF, and acting as a scaffold for cellular growth and invasion.
SSCI: Self-Supervised Deep Learning Improves Network Structure for Cancer Driver Gene Identification
Authors: Xu Jialuo , Hao Jun , Liao Xingyu , Shang Xuequn , Li Xingyi
Published: September 2024

The pathogenesis of cancer is complex, involving abnormalities in some genes in organisms. Accurately identifying cancer genes is crucial for the early detection of cancer and personalized treatment, among other applications. Recent studies have used graph deep learning methods to identify cancer driver genes based on biological networks. However, incompleteness and the noise of the networks will weaken the performance of models. To address this, we propose a cancer driver gene identification method based on self-supervision for graph convolutional networks, which can efficiently enhance the structure of the network and further improve predictive accuracy. The reliability of SSCI is verified by the area under the receiver operating characteristic curves (AUROC), the area under the precision-recall curves (AUPRC), and the F1 score, with respective values of 0.966, 0.964, and 0.913. The results show that our method can identify cancer driver genes with strong discriminative power and biological interpretability.
Possible Combinatorial Utilization of Phytochemicals and Extracellular Vesicles for Wound Healing and Regeneration
Authors: Koyama Sachiko , Weber Erin L. , Heinbockel Thomas
Published: September 2024

Organ and tissue damage can result from injury and disease. How to facilitate regeneration from damage has been a topic for centuries, and still, we are trying to find agents to use for treatments. Two groups of biological substances are known to facilitate wound healing. Phytochemicals with bioactive properties form one group. Many phytochemicals have anti-inflammatory effects and enhance wound healing. Recent studies have described their effects at the gene and protein expression levels, highlighting the receptors and signaling pathways involved. The extremely large number of phytochemicals and the multiple types of receptors they activate suggest a broad range of applicability for their clinical use. The hydrophobic nature of many phytochemicals and the difficulty with chemical stabilization have been a problem. Recent developments in biotechnology and nanotechnology methods are enabling researchers to overcome these problems. The other group of biological substances is extracellular vesicles (EVs), which are now known to have important biological functions, including the improvement of wound healing. The proteins and nanoparticles contained in mammalian EVs as well as the specificity of the targets of microRNAs included in the EVs are becoming clear. Plant-derived EVs have been found to contain phytochemicals. The overlap in the wound-healing capabilities of both phytochemicals and EVs and the differences in their nature suggest the possibility of a combinatorial use of the two groups, which may enhance their effects.
Integrative Analysis of Transcriptome and Metabolome Reveals the Pivotal Role of the NAM Family Genes in Oncidium hybridum Lodd. Pseudobulb Growth
Authors: Liu Yi , Zhu Qing , Wang Zukai , Zheng Haoyue , Zheng Xinyi , Ling Peng , Tang Minqiang
Published: September 2024

Oncidium hybridum Lodd. is an important ornamental flower that is used as both a cut flower and a potted plant around the world; additionally, its pseudobulbs serve as essential carriers for floral organs and flower development. The NAM gene family is crucial for managing responses to various stresses as well as regulating growth in plants. However, the mechanisms by which NAM genes regulate the development of pseudobulbs remain unclear. In this study, a total of 144 NAM genes harboring complete structural domains were identified in O. hybridum. The 144 NAM genes were systematically classified into 14 distinct subfamilies via phylogenetic analysis. Delving deeper into the conserved motifs revealed that motifs 1–6 exhibited remarkable conservation, while motifs 7–10 presented in a few NAM genes only. Notably, NAM genes sharing identical specific motifs were classified into the same subfamily, indicating functional relatedness. Furthermore, the examination of occurrences of gene duplication indicated that the NAM genes display 16 pairs of tandem duplications along with five pairs of segmental duplications, suggesting their role in genetic diversity and potential adaptive evolution. By conducting a correlation analysis integrating transcriptomics and metabolomics at four stages of pseudobulb development, we found that OhNAM023, OhNAM030, OhNAM007, OhNAM019, OhNAM083, OhNAM047, OhNAM089, and OhNAM025 exhibited significant relationships with the endogenous plant hormones jasmonates (JAs), hinting at their potential involvement in hormonal signaling. Additionally, OhNAM089, OhNAM025, OhNAM119, OhNAM055, and OhNAM136 showed strong links with abscisic acid (ABA) and abscisic acid glucose ester (ABA-GE), suggesting the possible regulatory function of these NAM genes in plant growth and stress responses. The 144 NAM genes identified in this study provide a basis for subsequent research and contribute to elucidating the intricate molecular mechanisms of NAM genes in Oncidium and potentially in other species.
A Novel Prognostic Model of Hepatocellular Carcinoma per Two NAD+ Metabolic Synthesis-Associated Genes
Authors: Dai Luo , Lu Shiliu , Mao Linfeng , Zhong Mingbei , Feng Gangping , He Songqing , Yuan Guandou
Published: September 2024

Hepatocellular carcinoma (HCC) is a formidable challenge to global human health, while recent years have witnessed the important role of NAD+ in tumorigenesis and progression. However, the expression pattern and prognostic value of NAD+ in HCC still remain elusive. Gene expression files and corresponding clinical pathological files associated with HCC were obtained from the Cancer Genome Atlas (TCGA) database, and genes associated with NAD+ were retrieved from the GSEA and differentially analyzed in tumor and normal tissues. A consensus clustering analysis was conducted by breaking down TCGA patients into four distinct groups, while Kaplan–Meier curves were generated to investigate the disparity in clinical pathology and endurance between clusters. A prognostic model based on NAD+-associated genes was established and assessed by combining LASSO-Cox regression, uni- and multi-variate Cox regression, and ROC curve analyses. Investigations were conducted to determine the expression of distinct mRNAs and proteins in both HCC and non-tumor tissues. A novel two-gene signature including poly (ADP-Ribose) polymerase 2 (PARP2) and sirtuin 6 (SIRT6) was obtained through LASSO-Cox regression and was identified to have favorable prognostic performance in HCC patients from TCGA. Analyses of both single and multiple variables showed that the prognostic model was a distinct prognostic factor in the endurance of liver cancer patients in both the training and trial groups. The nomogram also exhibited clinical significance in the prognosis of HCC patients. Immunohistochemistry, qRT-PCR, and Western blotting revealed that HCC samples exhibited higher PARP2 and SIRT6 expression levels than those of normal controls. This study identified a robust prognostic model comprising two NAD+-associated genes using bioinformatic methods, which is accurate in predicting the survival outcome of HCC patients. This model might benefit the early diagnosis of HCC and further facilitate the management of individualized medical service and clinical decision-making.
Vinblastine Resistance Is Associated with Nephronophthisis 3-Mediated Primary Cilia via Intraflagellar Transport Protein 88 and Apoptosis-Antagonizing Transcription Factor
Authors: Thuy Pham Xuan , Jang Tae-Kyu , Moon Eun-Yi
Published: September 2024

Primary cilia (PC) are microtubule-based organelles that function as cellular antennae to sense and transduce extracellular signals. Nephronophthisis 3 (NPHP3) is localized in the inversin compartment of PC. Mutations in NPHP3 are associated with renal-hepatic-pancreatic dysplasia. In this study, we investigated whether vinblastine (VBL), a microtubule destabilizer, induces anticancer drug resistance through NPHP3-associated PC formation in HeLa human cervical cancer cells. A considerable increase in PC frequency was observed in HeLa cells under serum-deprived (SD) conditions, which led to the inhibition of VBL-induced cell death. VBL-resistant cells were established by repetitive treatments with VBL and showed an increase in PC frequency. NPHP3 expression was also increased by VBL treatment under serum starvation as well as in VBL-resistant cells. NPHP3 expression and PC-associated resistance were positively correlated with apoptosis-antagonizing transcription factor (AATF) and negatively correlated with inhibition of NPHP3. In addition, AATF-mediated NPHP3 expression is associated with PC formation via the regulation of intraflagellar transport protein 88 (IFT88). VBL resistance ability was reduced by treating with ciliobrevin A, a well-known ciliogenesis inhibitor. Collectively, cancer cell survival following VBL treatment is regulated by PC formation via AATF-mediated expression of IFT88 and NPHP3. Our data suggest that the activation of AATF and IFT88 could be a novel regulator to induce anticancer drug resistance through NPHP3-associated PC formation.
Are BDNF and Stress Levels Related to Antidepressant Response?
Authors: Flores-Ramos Mónica , Vega-Rosas Andrés , Palomera-Garfias Nadia , Saracco-Alvarez Ricardo , Ramírez-Rodríguez Gerardo Bernabé
Published: September 2024

Antidepressant response is a multifactorial process related to biological and environmental factors, where brain-derived neurotrophic factor (BDNF) may play an important role in modulating depressive and anxious symptoms. We aimed to analyze how BDNF impacts antidepressant response, considering the levels of anxiety. Methods: A total of 40 depressed adults were included. We evaluated initial serum BDNF, anxiety through the State–Trait Anxiety Inventory (STAI), and the severity of depressive symptoms by the Hamilton Depression Rating Scale (HDRS). Participants received antidepressant treatment for 8 weeks, and response to treatment was evaluated according to the final HDRS scores. Results: Basal BDNF was higher in responders compared to non-responder depressed patients, in addition to being inversely associated with the severity of anxiety and depression. Conclusions: Baseline BDNF serum is an adequate predictive factor for response to antidepressant treatment with SSRI, with lower pre-treatment levels of BDNF associated with higher anxiety symptoms after treatment. Stress levels could influence the response to treatment, but its association was not conclusive.
Comprehensive Catalog of Variants Potentially Associated with Hidradenitis Suppurativa, Including Newly Identified Variants from a Cohort of 100 Patients
Authors: Muret Kévin , Le Goff Vincent , Dandine-Roulland Claire , Hotz Claire , Jean-Louis Francette , Boisson Bertrand , Mesrob Lilia , Sandron Florian , Daian Delphine , Olaso Robert , Le Floch Edith , Meyer Vincent , Wolkenstein Pierre , Casanova Jean-Laurent , Lévy Yves , Bonnet Eric , Deleuze Jean-François , Hüe Sophie
Published: September 2024

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases such as metabolic syndrome and inflammatory bowel disease. Genetic studies have identified mutations in the γ-secretase complex that affect Notch signaling pathways critical for skin cell regulation. Despite its high heritability, most reported HS cases do not follow a simple genetic pattern. In this article, we performed whole-exome sequencing (WES) on a cohort of 100 individuals with HS, and we provide a comprehensive review of the variants known to be described or associated with HS. 91 variants were associated with the γ-secretase complex, and 78 variants were associated with other genes involved in the Notch pathway, keratinization, or immune response. Through this new genetic analysis, we have added ten new variants to the existing catalogs. All variants are available in a .vcf file and are provided as a resource for future studies.
Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds
Authors: Lu Yan , Su Shanchun , Chu Chih-Chang , Kobayashi Yuichi , Masoud Abdul-Razak , Peng Hongying , Lien Nathan , He Mingyu , Vuong Christopher , Tran Ryan , Hong Song
Published: September 2024

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3°-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3° burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s), while PreM1-MVFs-ACgel1 was most effective with 97% closure and 4.69% relative epithelial gap at 13 dpb compared to saline control. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of 3°-burns although PreM1-MVFs-ACgel1 is significantly more effective. These PreM1- and/or MVF-functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapeutic candidates for treating deep burns.
Diabetic Mice Spleen Vulnerability Contributes to Decreased Persistence of Antibody Production after SARS-CoV-2 Vaccine
Authors: Atef Yara , Ito Tomoya , Masuda Akitsu , Kato Yuri , Nishimura Akiyuki , Kanda Yasunari , Kunisawa Jun , Kusakabe Takahiro , Nishida Motohiro
Published: September 2024

During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine′s safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients.
A Review of the Tear Film Biomarkers Used to Diagnose Sjogren’s Syndrome
Authors: Peng Jason , Feinstein David , DeSimone Salvatore , Gentile Pietro
Published: September 2024

This literature review looks at Sjogren’s Syndrome (SS), a chronic autoimmune disorder affecting exocrine glands, particularly the lacrimal and salivary glands. SS manifests as ocular and oral dryness, with severe complications like visual dysfunction and corneal perforation, as well as systemic implications, such as interstitial lung disease and lymphoma. This review explores the use of tear film biomarkers to diagnose SS, emphasizing the significance of their identification in aiding clinical diagnosis and differentiation from other diseases. This study identified and analyzed 15 papers, encompassing 1142 patients and employing various tear sample collection methods. Tear biomarkers were categorized by function and explored in-depth. Categories include (1) antimicrobials, antivirals, and antifungals; (2) components of immune regulation; (3) components that regulate metabolic processes; and (4) inflammatory markers. Noteworthy findings include the potential diagnostic values of tear lysozyme, lactoferrin, dinucleoside polyphosphates, cathepsin, defensin, antibodies, epidermal fatty acid-binding protein, HLA-DR, ADAM10, aquaporin 5, and various miRNAs and mRNAs. Overall, our understanding of SS tear film composition is enhanced, providing valuable insights into the pathogenesis of SS and offering a foundation for future diagnostic and therapeutic advancements in autoimmune conditions affecting the ocular surface.
Exploring the Potential of Neural Machine Translation for Cross-Language Clinical Natural Language Processing (NLP) Resource Generation through Annotation Projection
Authors: Rodríguez-Miret Jan , Farré-Maduell Eulàlia , Lima-López Salvador , Vigil Laura , Briva-Iglesias Vicent , Krallinger Martin
Published: September 2024

Recent advancements in neural machine translation (NMT) offer promising potential for generating cross-language clinical natural language processing (NLP) resources. There is a pressing need to be able to foster the development of clinical NLP tools that extract key clinical entities in a comparable way for a multitude of medical application scenarios that are hindered by lack of multilingual annotated data. This study explores the efficacy of using NMT and annotation projection techniques with expert-in-the-loop validation to develop named entity recognition (NER) systems for an under-resourced target language (Catalan) by leveraging Spanish clinical corpora annotated by domain experts. We employed a state-of-the-art NMT system to translate three clinical case corpora. The translated annotations were then projected onto the target language texts and subsequently validated and corrected by clinical domain experts. The efficacy of the resulting NER systems was evaluated against manually annotated test sets in the target language. Our findings indicate that this approach not only facilitates the generation of high-quality training data for the target language (Catalan) but also demonstrates the potential to extend this methodology to other languages, thereby enhancing multilingual clinical NLP resource development. The generated corpora and components are publicly accessible, potentially providing a valuable resource for further research and application in multilingual clinical settings.
Effect of Commercial Trap Design and Location on Captures of Diocalandra frumenti (Fabricius) (Coleoptera: Dryophthoridae) on Palm Trees
Authors: Ramos-Cordero Carina , Seris-Barrallo Elena , Vacas Sandra , Navarro-Llopis Vicente , Hernández-Suárez Estrella M.
Published: September 2024

Diocalandra frumenti (Fabricius) (Coleoptera: Dryophthoridae) is a weevil present in the Canary Islands, affecting economically important palms such as Phoenix canariensis H. Wildpret and its hybrids, for which there were no trapping tools. The larvae cause the main damage by burrowing galleries in the rachis of the leaves, causing premature drying and collapse. To develop an effective trap, six trials were carried out to evaluate the effect of trap type, design, colour, height, distance and location of the trap in relation to the palm tree on D. frumenti captures. This study confirms that the Econex® trap, green in colour, without a cover and with two ventilation holes of 2.5 cm in diameter, diametrically opposite each other and at 1 cm from the top of the base of the trap, baited with sugar cane and water, and placed between the first and second ring of green leaves of the palm canopy, is efficient in capturing D. frumenti. These results establish a basis for future research focused on the development of a specific trapping system based on semiochemicals to serve as a tool for detection, monitoring and mass trapping of D. frumenti.
Role of Serum Biomarkers in Differentiating Periprosthetic Joint Infections from Aseptic Failures after Total Hip Arthroplasties
Authors: Moldovan Flaviu
Published: September 2024

Background/Objectives: Periprosthetic joint infection (PJI) is a disastrous complication after joint replacement procedures as the diagnosis remains a significant challenge. The objective of this study is to assess the accuracy and test the interdependency of the proposed compound serum biomarkers for the diagnosis of PJI after total hip arthroplasties (THA). Methods: From January 2019 to December 2023, 77 consecutive cases that underwent revision total hip arthroplasties (rTHA) were included in a single−retrospective, observational cohort study. A total of 32 arthroplasties were classified as having septic complications using the European Bone and Joint Infection Society (EBJIS) definition from 2021, while the other 45 cases were assigned as aseptic failures (AF). Results: In the univariate analysis between the two groups created, statistically significant differences (p < 0.005) were found for the following variables: time from primary arthroplasty to symptom onset (Time PA−SO), neutrophil count, Lymphocyte count, haematocrit level (HCT) and haemoglobin level (HGB), C−reactive protein (CRP), the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI). The ROC curve analysis showed that the SII (sensitivity 90.6% and specificity 62.2%) and the NLR (sensitivity 84.4% and specificity 64.4%) are the most accurate biomarkers. The multivariate analysis confirmed that NLR > 2.63 (p = 0.006), PLR > 147 (p = 0.021), MLR > 0.31 (p = 0.028), SII > 605.31 (p = 0.002), SIRI > 83.34 (p = 0.024), and AISI > 834.86 (p = 0.011) are all closely related to PJI diagnosis independently. Conclusions: The proposed serum biomarkers can be correlated with PJI diagnosis with the reserve of relatively low specificities.
Settings and Clinical Applications of Subthreshold Micropulse Laser Therapy: A Review
Authors: Sorrentino Tania , Allegrini Davide , De Rosa Giacomo , Santoru Francesco , Crepaldi Lorenzo , Feo Alessandro , Zanellati Giacomo , Marconi Stefania , Auricchio Ferdinando , Romano Mario R.
Published: September 2024

Subthreshold lasers operate below the threshold of visible tissue damage, thereby preventing ophthalmoscopically visible thermal damage to the chorio-retinal layers. They could represent a safe and effective alternative and/or adjunctive procedure to conventional lasers in treating diabetic macula edema (DME), central serous chorioretinopathy (CSCR), and branch retina vein occlusion (BRVO). This review focuses on the use of subthreshold micropulse laser (SMPL), its settings, and clinical applications. Despite their widespread use, a standardized protocol for sub-threshold laser settings has not been established yet, and thus, there is uncertainty in selecting effective and safe parameters for any specific situation. We conducted a comprehensive overview of the existing indications for subthreshold laser therapy and their settings for different retinal diseases. The debate revolves around which parameters could guarantee the safety of the procedure for each case, depending on the duty cycle, the laser wavelength, the spot duration, and the power, with laser power titration on one side or choosing a fixed lowered power value on the other side. SMPL therapy for DME, CSCR, and BRVO-associated macular edema has shown significant effectiveness in reducing the macular thickness, facilitating subretinal fluid absorptions, increasing the best corrected visual acuity (BCVA) and reducing the number of intravitreal injections (IVI) required annually. We presented a broad list of the laser parameters reported in the literature, organized into different tables divided based on the specific pathology, with the aim of providing a useful tool for future studies.
Impact of Non-Alcoholic Fatty Liver Disease on Sepsis Inpatient Outcomes: A Nationwide Sample Analysis (2000–2019)
Authors: Lyu Xiuhong , Liu Bolun , Li Yiting , Wang Yichen , Miskovsky John , Gaitanis Melissa , Promrat Kittichai , Wu Wen-Chih
Published: September 2024

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD’s impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes.
The Suboptimal QLV Ratio May Indicate the Need for a Left Bundle Branch Area Pacing-Optimized Cardiac Resynchronization Therapy Upgrade
Authors: Ezer Péter , Szűcs Kitti , Lukács Réka , Bisztray Tamás , Vilmányi Gábor , Szokodi István , Komócsi András , Kónyi Attila
Published: September 2024

Background: The QLV ratio (QLV/baseline QRS width) is an established intraoperative-measurable parameter during cardiac resynchronization therapy (CRT) device implantation, potentially predicting the efficacy of electrical resynchronization. Methods: Left bundle branch area pacing-optimized CRT (LOT-CRT) is a novel approach with the potential to improve both responder rate and responder level in the CRT candidate patient group, even when an optimal electro-anatomical left ventricular lead position is not achievable. In our observational study, 72 CRT-defibrillator candidate patients with a QRS duration of 160 ± 12 ms were consecutively implanted. Using a QLV-ratio-based implant strategy, 40 patients received a biventricular CRT device (Biv-CRT) with an optimal QLV ratio (≥70%). Twenty-eight patients with a suboptimal QLV ratio (<70%) were upgraded intraoperatively to a LOT-CRT system. Patients were followed for 12 months. Results: The postoperative results showed a significantly greater reduction in QRS width in the LOT-CRT patient group compared to the Biv-CRT patients (40.4 ± 14 ms vs. 32 ± 13 ms; p = 0.024). At 12 months, the LOT-CRT group also demonstrated a significantly greater improvement in left ventricular ejection fraction (14.9 ± 8% vs. 10.3 ± 7.4%; p = 0.001), and New York Heart Association functional class (1.2 ± 0.5 vs. 0.8 ± 0.4; p = 0.031), and a significant decrease in NT-pro-BNP levels (1863± 380 pg/mL vs. 1238 ± 412 pg/mL; p = 0.012). Notably, the LOT-CRT patients showed results comparable to Biv-CRT patients with a super-optimal QLV ratio (>80%) in terms of QRS width reduction and LVEF improvement. Conclusions: Our single-center study demonstrated the feasibility of a QLV-ratio-based implantation strategy during CRT implantation. Patients with a LOT-CRT system showed significant improvements, whereas Biv-CRT patients with a super-optimal QLV ratio may not be expected to benefit from an additional LOT-CRT upgrade.
Recurrent Ischemic Stroke and Transient Ischemic Attack: Risk of Single and Multiple Recurrence
Authors: Park Moon-Ho , Lee Sang-Hun , Jung Jin-Man
Published: September 2024

Background/Objectives: Efforts have been made toward primary or secondary stroke or transient ischemic attack (TIA) prevention. However, little attention has been paid to recurrent stroke or TIA. This study investigated risk factors for multiple or single recurrent stroke or TIA. Methods: Data from 3646 patients with ischemic stroke or TIA were obtained from the Korea University Ansan Hospital Stroke Center between March 2014 and December 2021, using the prospective institutional database of the Korea University Stroke Registry. The associations between clinical features and recurrent stroke or TIA were assessed using bivariable and multivariable Cox models. Results: Recurrent stroke or TIA was associated with male sex (adjusted hazard ratio (HR) 1.95, 95% confidence interval (CI) 1.42–2.80), hypertension (HR 1.49, 95% CI 1.00–2.23), diabetes mellitus (HR 1.54, 95% CI 1.13–2.13), an etiologic subtype of transient ischemic attack (HR 1.88, 95% CI 1.09–3.16), white matter changes (HR 1.62, 95% CI 1.05–2.38), and cerebral microbleeds (HR 1.79, 95% CI 1.26–2.59). Multiple recurrent stroke or TIA was associated with male sex (HR 3.86, 95% CI 1.94–11.55), diabetes mellitus (HR 2.40, 95% CI 1.31–4.53), and anemia (HR 4,58, 95% CI 2.31–10.44). Conclusions: Given the risk factor profiles for recurrent stroke or TIA, risks differed among patient subgroups and were based on multiple or single recurrences. It may exert an effect as a prognostic indicator in the high risk of recurrences.
Security Operations Centers: Use Case Best Practices, Coverage, and Gap Analysis Based on MITRE Adversarial Tactics, Techniques, and Common Knowledge
Authors: Chamkar Samir Achraf , Maleh Yassine , Gherabi Noreddine
Published: September 2024

The rising frequency and complexity of cybersecurity threats necessitate robust monitoring and rapid response capabilities to safeguard digital assets effectively. As a result, many organizations are increasingly establishing Security Operations Centers (SOCs) to actively detect and respond to cybersecurity incidents. This paper addresses the intricate process of setting up a SOC, emphasizing the need for careful planning, substantial resources, and a strategic approach. This study outlines the essential steps involved in defining the SOC’s objectives and scope, selecting appropriate technologies, recruiting skilled cybersecurity professionals, and developing processes throughout the SOC lifecycle. This paper aims to provide a comprehensive understanding of the SOC’s threat detection capabilities and use cases. It also highlights the importance of choosing technologies that integrate seamlessly with existing IT infrastructure to ensure broad coverage of SOC activities. Furthermore, this study offers actionable insights for organizations looking to enhance their SOC capabilities, including a technical overview of SOC use case coverage and a gap assessment of detection rules. This assessment is based on an alignment with the MITRE ATT&CK framework and an analysis of events generated by the company’s existing IT devices and products. The findings from this research elucidate the indispensable role that SOCs play in bolstering organizational cybersecurity and resilience.
Information Recognition and Recall in Older Adults Bearing Vascular Risk Factors with or without Diagnosis of Mild Cognitive Impairment
Authors: Tsentidou Glykeria , Moraitou Despina , Masoura Elvira , Metallidou Panayiota , Papadopoulos Efstathios , Papaliagkas Vasileios , Tsolaki Magda
Published: September 2024

Episodic memory is affected early and is a basic indication of neurodegeneration especially for Alzheimer’s disease. The aim of this study was to examine whether adults with vascular risk factors are differentiated in their episodic memory performance from individuals with mild cognitive impairment (MCI). The episodic memory of adults diagnosed with MCI, adults with vascular risk factors (VRF; blood pressure, diabetes mellitus, or hypercholesterolemia), and healthy controls was assessed using the Doors and People test. Statistical processing included mediation analyses which were performed separately for the VRF and healthy control groups, and the MCI and healthy control groups. ANOVA was used for the MCI and VRF groups which were matched in age and education. ANOVA showed that the MCI adults had significantly lower performance than the VRF adults in verbal recall only, F (1, 83) = 9.541, p = 0.003, and ηp2 = 0.10. A direct effect of diagnosis on verbal recall was found via mediation analysis as concerns individuals with MCI and healthy controls, b = 0.506, SE = 0.128, p < 0.001, and 95%CI: 0.221–0.771, in favor of the healthy controls. Concerning the VRF and healthy groups, a tendency of diagnosis to directly affect verbal recall was shown (α = 0.005) in favor of the healthy controls, b = 0.388, SE = 0.150, p = 0.010, and 95%CI: 0.043–0.720. In conclusion, it is supported that patients with MCI present deficit performance in verbal recall; in addition, the diagnostic category affects all the groups’ performance on the same condition. These results indicated that the verbal recall aspect of episodic memory can be a sensitive indicator that can differentiate healthy adults from adults with mild cognitive impairment and vascular risk factors, as well as the two pathological groups from each other.
Evaluating the Effects of BSA-Coated Gold Nanorods on Cell Migration Potential and Inflammatory Mediators in Human Dermal Fibroblasts
Authors: Mahmoud Nouf N. , Hammad Ayat S. , Al Kaabi Alaya S. , Alawi Hend H. , Khatoon Summaiya , Al-Asmakh Maha
Published: September 2024

Albumin-coated gold nanoparticles display potential biomedical applications, including cancer research, infection treatment, and wound healing; however, elucidating their interaction with normal cells remains an area with limited exploration. In this study, gold nanorods (GNR) were prepared and coated with bovine serum albumin (BSA) to produce GNR-BSA. The functionalized nanoparticles were characterized based on their optical absorption spectra, morphology, surface charge, and quantity of attached protein. The interaction between GNR-BSA and BSA with normal cells was investigated using human dermal fibroblasts. The cytotoxicity test indicated cell viability between ~63–95% for GNR-BSA over concentrations from 30.0 to 0.47 μg/mL and ~85–98% for BSA over concentrations from 4.0 to 0.0625 mg/mL. The impact of the GNR-BSA and BSA on cell migration potential and wound healing was assessed using scratch assay, and the modulation of cytokine release was explored by quantifying a panel of cytokines using Multiplex technology. The results indicated that GNR-BSA, at 10 μg/mL, delayed the cell migration and wound healing 24 h post-treatment compared to the BSA or the control group with an average wound closure percentage of 6% and 16% at 6 and 24 h post-treatment, respectively. Multiplex analysis revealed that while GNR-BSA reduced the release of the pro-inflammatory marker IL-12 from the activated fibroblasts 24 h post-treatment, they significantly reduced the release of IL-8 (p < 0.001), and CCL2 (p < 0.01), which are crucial for the inflammation response, cell adhesion, proliferation, migration, and angiogenesis. Although GNR-BSA exhibited relatively high cell viability towards human dermal fibroblasts and promising therapeutic applications, toxicity aspects related to cell motility and migration must be considered.