bluuebunny/crossref_metadata_2025 huggingface dataset:
Interconnections between the Gut Microbiome and Alzheimer’s Disease: Mechanisms and Therapeutic Potential
Authors: Sait Ahmad M. , Day Philip J. R.
Published: August 2024

Alzheimer’s disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-β (Aβ) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The Aβ monoclonal antibody lecanemab reduces Aβ plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood–brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.
Genomic Analysis of Cronobacter condimenti s37: Identification of Resistance and Virulence Genes and Comparison with Other Cronobacter and Closely Related Species
Authors: Berthold-Pluta Anna , Stefańska Ilona , Forsythe Stephen , Aleksandrzak-Piekarczyk Tamara , Stasiak-Różańska Lidia , Garbowska Monika
Published: August 2024

Cronobacter condimenti are environmental commensals that have not been associated with any clinical infections. To date, they are the least understood and described Cronobacter species within the genus. The objective of this study was to use a draft genome sequence (DGS) of the Cronobacter condimenti strain s37 to screen for genes encoding for antibiotic resistance, virulence, response to environmental stress, and biofilm formation. The strain was isolated in Poland from commercial small radish sprouts. This is the second genome of this species available in the GenBank database. The comparative genome analysis (cgMLST) of C. condimenti s37 with other Cronobacter spp. including the pathogenic species C. sakazakii and the plant-associated closely related genera Franconibacter and Siccibacter was also performed. The assembled and annotated genome of the C. condimenti s37 genome was 4,590,991 bp in length, with a total gene number of 4384, and a GC content of 55.7%. The s 37 genome encoded for genes associated with resistance to stressful environmental conditions (metal resistance genes: zinc, copper, osmotic regulation, and desiccation stress), 17 antimicrobial resistance genes encoding resistance to various classes of antibiotics and 50 genes encoding for the virulence factors. The latter were mainly genes associated with adhesion, chemotaxis, hemolysis, and biofilm formation. Cg-MLST analysis (3991 genes) revealed a greater similarity of C. condimenti s37 to S. turicensis, F. pulveris, and C. dublinensis than to other species of the genus Cronobacter. Studies on the diversity, pathogenicity, and virulence of Cronobacter species isolated from different sources are still insufficient and should certainly be continued. Especially the analysis of rare strains such as s37 is very important because it provides new information on the evolution of these bacteria. Comparative cgMLST analysis of s37 with other Cronobacter species, as well as closely related genera Franconibacter and Siccibacter, complements the knowledge on their adaptability to specific environments such as desiccation.
A Comprehensive Exploration of the Multifaceted Neuroprotective Role of Cannabinoids in Alzheimer’s Disease across a Decade of Research
Authors: Tyrakis Petros , Agridi Christina , Kourti Malamati
Published: August 2024

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests through dysregulation of brain function and subsequent loss of bodily control, attributed to β-amyloid plaque deposition and TAU protein hyperphosphorylation and aggregation, leading to neuronal death. Concurrently, similar cannabinoids to the ones derived from Cannabis sativa are present in the endocannabinoid system, acting through receptors CB1R and CB2R and other related receptors such as Trpv-1 and GPR-55, and are being extensively investigated for AD therapy. Given the limited efficacy and adverse effects of current available treatments, alternative approaches are crucial. Therefore, this review aims to identify effective natural and synthetic cannabinoids and elucidate their beneficial actions for AD treatment. PubMed and Scopus databases were queried (2014–2024) using keywords such as “Alzheimer’s disease” and “cannabinoids”. The majority of natural (Δ9-THC, CBD, AEA, etc.) and synthetic (JWH-133, WIN55,212-2, CP55-940, etc.) cannabinoids included showed promise in improving memory, cognition, and behavioral symptoms, potentially via pathways involving antioxidant effects of selective CB1R agonists (such as the BDNF/TrkB/Akt pathway) and immunomodulatory effects of selective CB2R agonists (TLR4/NF-κB p65 pathway). Combining anticholinesterase properties with a cannabinoid moiety may enhance therapeutic responses, addressing cholinergic deficits of AD brains. Thus, the positive outcomes of the vast majority of studies discussed support further advancing cannabinoids in clinical trials for AD treatment.
The Effect of Phototherapy on Systemic Inflammation Measured with Serum Vitamin D-Binding Protein and hsCRP in Patients with Inflammatory Skin Disease
Authors: Elmelid Andrea , Vandikas Maria Siekkeri , Gillstedt Martin , Alsterholm Mikael , Osmancevic Amra
Published: August 2024

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.
Advances in Millimeter-Wave Treatment and Its Biological Effects Development
Authors: Jing Rui , Jiang Zhenqi , Tang Xiaoying
Published: August 2024

This comprehensive review critically examines the current state of research on the biological effects of millimeter-wave (MMW) therapy and its potential implications for disease treatment. By investigating both the thermal and non-thermal impacts of MMWs, we elucidate cellular-level alterations, including changes in ion channels and signaling pathways. Our analysis encompasses MMW’s therapeutic prospects in oncology, such as inducing apoptosis, managing pain, and modulating immunity through cytokine regulation and immune cell activation. By employing a rigorous methodology involving an extensive database search and stringent inclusion criteria, we emphasize the need for standardized protocols to enhance the reliability of future research. Although MMWs exhibit promising therapeutic potential, our findings highlight the urgent need for further elucidation of non-thermal mechanisms and rigorous safety assessments, considering the intricate nature of MMW interactions and inconsistent study outcomes. This review underscores the importance of focused research on the biological mechanisms of MMWs and the identification of optimal frequencies to fully harness their therapeutic capabilities. However, we acknowledge the challenges of variable study quality and the necessity for advanced quality control measures to ensure the reproducibility and comparability of future investigations. In conclusion, while MMW therapy holds promise as a novel therapeutic modality, further research is imperative to unravel its complex biological effects, establish safety profiles, and optimize treatment protocols before widespread clinical application.
Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival
Authors: Talarico Maria Cecília Ramiro , Derchain Sophie , da Silva Lucas Ferreira , Sforça Maurício L. , Rocco Silvana A. , Cardoso Marcella R. , Sarian Luís Otávio
Published: August 2024

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51–7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64–6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.
TFIIB–Termination Factor Interaction Affects Termination of Transcription on Genome-Wide Scale
Authors: O’Brien Michael J. , Schrader Jared M. , Ansari Athar
Published: August 2024

Apart from its well-established role in the initiation of transcription, the general transcription factor TFIIB has been implicated in the termination step as well. The ubiquity of TFIIB involvement in termination as well as mechanistic details of its termination function, however, remain largely unexplored. Using GRO-seq analyses, we compared the terminator readthrough phenotype in the sua7-1 mutant (TFIIBsua7-1) and the isogenic wild type (TFIIBWT) strains. Approximately 74% of genes analyzed exhibited a 2-3-fold increase in readthrough of the poly(A)-termination signal in the TFIIBsua7-1 mutant compared to TFIIBWT cells. To understand the mechanistic basis of TFIIB’s role in termination, we performed the mass spectrometry of TFIIB—affinity purified from chromatin and soluble cellular fractions—from TFIIBsua7-1 and TFIIBWT cells. TFIIB purified from the chromatin fraction of TFIIBWT cells exhibited significant enrichment of CF1A and Rat1 termination complexes. There was, however, a drastic decrease in TFIIB interaction with CF1A and Rat1 complexes in the TFIIBsua7-1 mutant. ChIP assays revealed about a 90% decline in the recruitment of termination factors in the TFIIBsua7-1 mutant compared to wild type cells. The overall conclusion of these results is that TFIIB affects the termination of transcription on a genome-wide scale, and the TFIIB–termination factor interaction plays a crucial role in the process.
Effects of PCNA Stability on the Formation of Mutations
Authors: Arbel-Groissman Matan , Liefshitz Batia , Kupiec Martin
Published: August 2024

The fidelity of replication, especially in the presence of DNA damage, is essential for the proper function of cells. Mutations that inactivate genes involved in DNA damage repair or bypass are enriched in several types of cancer cells. Thus, it is important to further our understanding of the mechanisms governing replication fidelity. PCNA is a ring-shaped complex that encircles DNA at the front of the replication fork, at the double-stranded/single-stranded DNA junction. It serves as a processivity factor for the different DNA replication polymerases, allowing them to replicate longer stretches of DNA by physically tethering them to the DNA and preventing their detachment. In addition, PCNA also regulates and coordinates different DNA damage bypass pathways meant to allow DNA replication in the presence of DNA damage. Due to its essentiality and the numerous functions it has in the cell, much is still unclear about PCNA. Here, we utilize PCNA mutants that lower the stability of the PCNA complex on the chromatin, and thus tend to disassociate and fall from the DNA. Using these mutants, we show that PCNA’s physical presence on the DNA can prevent DNA misalignment at repetitive sequences, leading to increased mutation formation. We also show that PCNA-interacting proteins play an important role in strengthening the ring’s stability on the chromatin. Such repetitive sequence-induced mutations are common in several human diseases and it is important to study their formation and the mechanisms guarding against them.
Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer
Authors: Kovale Lochana , Singh Manish Kumar , Kim Joungmok , Ha Joohun
Published: August 2024

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, as certain cancers tend to depend on autophagy for survival. Autophagy, while crucial for maintaining stemness in cancer stem cells (CSCs), can also serve as a vulnerability in certain contexts, making it a complex target for therapy. Regulators of autophagy like AMPK (5′ adenosine monophosphate-activated protein kinase) also play a crucial role in maintaining CSCs stemness by helping CSCs in metabolic reprogramming in harsh environments. The purpose of this review is to elucidate the interplay between autophagy and AMPK in CSCs, highlighting the challenges in targeting autophagy and discussing therapeutic strategies to overcome these limitations. This review focuses on previous research on autophagy and its regulators in cancer biology, particularly in CSCs, addresses the remaining unanswered questions, and potential targets for therapy are also brought to attention.
Intestinal Dysbiosis, Tight Junction Proteins, and Inflammation in Rheumatoid Arthritis Patients: A Cross-Sectional Study
Authors: Mucientes Arkaitz , Lisbona-Montañez José Manuel , Mena-Vázquez Natalia , Ruiz-Limón Patricia , Manrique-Arija Sara , García-Studer Aimara , Ortiz-Márquez Fernando , Fernández-Nebro Antonio
Published: August 2024

Recent studies point to intestinal permeability as an important factor in the establishment and development of rheumatoid arthritis (RA). Tight junctions (TJs) play a major role in intestinal homeostasis. The alteration of this homeostasis is related to RA. Furthermore, RA patients present dysbiosis and a lower microbiota diversity compared to healthy individuals. A cross-sectional study including RA patients and sex- and age-matched healthy controls was performed. The quantification of TJ proteins was carried out by ELISA. Gut microbiota was evaluated by NGS platform Ion Torrent S. The inflammatory variables included were DAS28, CRP, inflammatory cytokines (IL-6, IL-1, TNF-α) and oxidised LDL. Claudin-1 levels showed significant differences between groups. Results evidenced a correlation between claudin-1 values and age (r: −0.293; p < 0.05), IL6 (r: −0.290; p < 0.05) and CRP (r: −0.327; p < 0.05), and between zonulin values and both age (r: 0.267; p < 0.05) and TNFα (r: 0.266; p < 0.05). Moreover, claudin-1 and CRP levels are related in RA patients (β: −0.619; p: 0.045), and in patients with high inflammatory activity, the abundance of the genus Veillonella is positively associated with claudin-1 levels (β: 39.000; p: 0.004).
Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads
Authors: Tonon Giovanni , Rizzolio Flavio , Visentin Fabiano , Scattolin Thomas
Published: August 2024

This review highlights significant advancements in antibody–drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients.
The Impact of Extracellular Histones and Absence of Toll-like Receptors on Cardiac Functional and Electrical Disturbances in Mouse Hearts
Authors: Loaiza Randall , Fattahi Fatemeh , Kalbitz Miriam , Grailer Jamison J. , Russell Mark W. , Jalife Jose , Valdivia Hector H. , Zetoune Firas S. , Ward Peter A.
Published: August 2024

In polymicrobial sepsis, the extracellular histones, mainly released from activated neutrophils, significantly contribute to cardiac dysfunction (septic cardiomyopathy), as demonstrated in our previous studies using Echo-Doppler measurements. This study aims to elucidate the roles of extracellular histones and their interactions with Toll-like receptors (TLRs) in cardiac dysfunction. Through ex vivo assessments of ECG, left ventricle (LV) function parameters, and in vivo Echo-Doppler studies in mice perfused with extracellular histones, we aim to provide comprehensive insights into the mechanisms underlying sepsis-induced cardiac dysfunction. Langendorff-perfused hearts from both wild-type and TLR2, TLR3, or TLR4 knockout (KO) mice were examined. Paced mouse hearts were perfused with histones to assess contractility and relaxation. Echo-Doppler studies evaluated cardiac dysfunction after intravenous histone injection. Histone perfusion caused defects in contractility and relaxation, with TLR2 and TLR3 KO mice being partially protected. Specifically, TLR2 KO mice exhibited the greatest reduction in Echo-Doppler abnormalities, while TLR4 KO exacerbated cardiac dysfunction. Among individual histones, H1 induced the most pronounced abnormalities in cardiac function, apoptosis of cardiomyocytes, and LDH release. Our data highlight significant interactions between histones and TLRs, providing insights into histones especially H1 as potential therapeutic targets for septic cardiomyopathy. Further studies are needed to explore specific histone–TLR interactions and their mechanisms.
Integrating 16S rRNA Sequencing, Microflora Metabolism, and Network Pharmacology to Investigate the Mechanism of SBL in Alleviating HDM-Induced Allergic Rhinitis
Authors: Li Peiting , Hon Sharon Sze-Man , Tsang Miranda Sin-Man , Kan Lea Ling-Yu , Lai Andrea Yin-Tung , Chan Ben Chung-Lap , Leung Ping-Chung , Wong Chun-Kwok
Published: August 2024

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis.
Behavior of Assembled Promyelocytic Leukemia Nuclear Bodies upon Asymmetric Division in Mouse Oocytes
Authors: Udagawa Osamu , Kato-Udagawa Ayaka , Hirano Seishiro
Published: August 2024

Promyelocytic leukemia (PML) nuclear bodies (PML-NBs) are core–shell-type membrane-less organelles typically found in the nucleus of mammalian somatic cells but are absent in mouse oocytes. Here, we deliberately induced the assembly of PML-NBs by injecting mRNA encoding human PML protein (hPML VI -sfGFP) into oocytes and investigated their impact on fertilization in which oocyte/embryos undergo multiple types of stresses. Following nuclear membrane breakdown, preassembled hPML VI -sfGFP mRNA-derived PML-NBs (hmdPML-NBs) persisted in the cytoplasm of oocytes, forming less-soluble debris, particularly under stress. Parthenogenetic embryos that successfully formed pronuclei were capable of removing preassembled hmdPML-NBs from the cytoplasm while forming new hmdPML-NBs in the pronucleus. These observations highlight the beneficial aspect of the PML-NB-free nucleoplasmic environment and suggest that the ability to eliminate unnecessary materials in the cytoplasm of metaphase oocytes serves as a potential indicator of the oocyte quality.
Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin
Authors: Gliga Maximilian Cosma , Chinezu Laura , Pascanu Ionela Maria
Published: August 2024

Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = −0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.
Progress of Exosomal LncRNAs in Pancreatic Cancer
Authors: Wei Chengyan , Zhang Chunwei , Zhou Yuanzhi , Wang Jingjing , Jin Yong
Published: August 2024

Pancreatic cancer is a prevalent malignant tumor with rising medication resistance and mortality. Due to a dearth of specific and trustworthy biomarkers and therapeutic targets, pancreatic cancer early detection and treatment are still not at their best. Exosomal LncRNAs have been found to be plentiful and persistent within exosomes, and they are capable of functioning whether the exosomes are traveling to close or distant cells. Furthermore, increasing evidence suggests that exosomal LncRNA, identified as an oncogene or tumor suppressor-control the growth, metastasis, and susceptibility of pancreatic cancer to chemotherapy and radiation therapy. Promising prospects for both antitumor targets and diagnostic biomarkers are exosomal LncRNAs. The primary features of exosomal LncRNAs, their biological roles in the onset and progression of pancreatic cancer, and their potential as therapeutic targets and diagnostic molecular markers are outlined in this review.
Impact of Extrusion Parameters on the Formation of Nε-(Carboxymethyl)lysine, Nε-(Carboxyethyl)lysine and Acrylamide in Plant-Based Meat Analogues
Authors: Ma Yurong , Fu Shuang , Cheng Ka-Wing , Liu Bin
Published: August 2024

To investigate the impact of extrusion parameters on the formation of Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL) and acrylamide in plant-based meat analogues (PBMAs), the content changes and the correlations of compounds related to their formation were studied. The extrusion promoted CML, CEL and acrylamide formation, with more CEL being formed than CML. Variations in the moisture level and barrel temperature exerted a greater influence on the CML, CEL, acrylamide and α-dicarbonyl compounds than the screw speed and the feed rate. An increase in the moisture content led to a decrease in the CEL content, whereas it enhanced CML formation. The impact of moisture on acrylamide formation varied depending on whether low- or high-moisture extrusion was applied. Elevated temperatures promoted the accumulation of CEL, methylglyoxal and 2,3-butanedione while diminishing the accumulation of CML, acrylamide, glyoxal and 3-deoxyglucosone. CML and CEL were positively correlated with glyoxal and methylglyoxal, respectively. CEL and methylglyoxal were negatively correlated with protein and water content, whereas CML, glyoxal and 3-deoxyglucosone displayed positive correlations. In summary, higher moisture levels and feed rates and lower screw speeds and barrel temperatures are advantageous for producing PBMAs with lower CEL and total advanced glycation end-products contents, while lower or higher moisture contents, a lower feed rate and a higher barrel temperature are beneficial to reducing the acrylamide content.
The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer
Authors: Chan Wei Yen , Chua Wei , Wilkinson Kate , Epitakaduwa Chandika , Mandaliya Hiren , Descallar Joseph , Roberts Tara Laurine , Becker Therese Maria , Ng Weng , Lee Cheok Soon , Lim Stephanie Hui-Su
Published: August 2024

Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I–IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2’s relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.
Ss4368: Pathogen-Associated Molecular Pattern for Inducing Plant Cell Death and Resistance to Phytophthora capsici
Authors: He Ziwen , Peng Shufang , Yin Qingqing , Huang Yuanyuan , Deng Ting , Luo Yiwei , He Ningjia
Published: August 2024

Plant recognition of pathogen-associated molecular patterns (PAMPs) is pivotal in triggering immune responses, highlighting their potential as inducers of plant immunity. However, the number of PAMPs identified and applied in such contexts remains limited. In this study, we characterize a novel PAMP, designated Ss4368, which is derived from Scleromitrula shiraiana. Ss4368 is specifically distributed among a few fungal genera, including Botrytis, Monilinia, and Botryotinia. The transient expression of Ss4368 elicits cell death in a range of plant species. The signaling peptides, three conserved motifs, and cysteine residues (C46, C88, C112, C130, and C148) within Ss4368 are crucial for inducing robust cell death. Additionally, these signaling peptides are essential for the protein’s localization to the apoplast. The cell death induced by Ss4368 and its homologous protein, Bc4368, is independent of the SUPPRESSOR OF BIR1-1 (SOBIR1), BRI1-ASSOCIATED KINASE-1 (BAK1), and salicylic acid (SA) pathways. Furthermore, the immune responses triggered by Ss4368 and Bc4368 significantly enhance the resistance of Nicotiana benthamiana to Phytophthora capsici. Therefore, we propose that Ss4368, as a novel PAMP, holds the potential for developing strategies to enhance plant resistance against P. capsici.
Omega-3 Polyunsaturated Fatty Acids in Depression
Authors: Serefko Anna , Jach Monika Elżbieta , Pietraszuk Marlena , Świąder Małgorzata , Świąder Katarzyna , Szopa Aleksandra
Published: August 2024

Omega-3 polyunsaturated fatty acids have received considerable attention in the field of mental health, in particular regarding the treatment of depression. This review presents an overview of current research on the role of omega-3 fatty acids in the prevention and treatment of depressive disorders. The existing body of evidence demonstrates that omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant effects that can be attributed to their modulation of neuroinflammation, neurotransmitter function, and neuroplasticity. Nevertheless, clinical trials of omega-3 supplementation have yielded inconsistent results. Some studies have demonstrated significant reductions in depressive symptoms following omega-3 treatment, whereas others have shown minimal to no beneficial impact. A range of factors, encompassing dosage, the ratio of EPA to DHA, and baseline nutritional status, have been identified as having a potential impact on the noted results. Furthermore, it has been suggested that omega-3 fatty acids may act as an adjunctive treatment for those undergoing antidepressant treatment. Notwithstanding these encouraging findings, discrepancies in study designs and variability in individual responses underscore the necessity of further research in order to establish uniform, standardized guidelines for the use of omega-3 fatty acids in the management of depressive disorders.
mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes
Authors: Troise Dario , Mercuri Silvia , Infante Barbara , Losappio Vincenzo , Cirolla Luciana , Netti Giuseppe Stefano , Ranieri Elena , Stallone Giovanni
Published: August 2024

The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells. Among them, mTOR and SGLT-2 inhibitors have garnered attention due to their diverse effects: mTOR inhibitors regulate cellular growth, metabolism, and immune responses, while SGLT-2 inhibitors regulate glucose reabsorption in the kidneys, resulting in various beneficial metabolic effects. Importantly, these drugs may act synergistically by influencing senescence processes and pathways. Although direct studies on the combined effects of mTOR inhibition and SGLT-2 inhibition on age-related processes are limited, this review aims to highlight the potential synergistic benefits of these drugs in targeting senescence.
A Comprehensive Study on Unsupervised Transfer Learning for Structural Health Monitoring of Bridges Using Joint Distribution Adaptation
Authors: Souza Laura , Yano Marcus Omori , da Silva Samuel , Figueiredo Eloi
Published: August 2024

Bridges are crucial transportation infrastructures with significant socioeconomic impacts, necessitating continuous assessment to ensure safe operation. However, the vast number of bridges and the technical and financial challenges of maintaining permanent monitoring systems in every single bridge make the implementation of structural health monitoring (SHM) difficult for authorities. Unsupervised transfer learning, which reuses experimental or numerical data from well-known bridges to detect damage on other bridges with limited monitoring response data, has emerged as a promising solution. This solution can reduce SHM costs while ensuring the safety of bridges with similar characteristics. This paper investigates the limitations, challenges, and opportunities of unsupervised transfer learning via domain adaptation across datasets from various prestressed concrete bridges under distinct operational and environmental conditions. A feature-based transfer learning approach is proposed, where the joint distribution adaptation method is used for domain adaptation. As the main advantage, this study leverages the generalization of SHM for damage detection in prestressed concrete bridges with limited long-term monitoring data.
Early versus Late Radiofrequency Catheter Ablation in Atrial Fibrillation: Timing Matters
Authors: Farghaly Ahmad A. A. , Ali Hussam , Lupo Pierpaolo , Foresti Sara , De Ambroggi Guido , Atta Salah , Abdel-Galeel Ahmed , Tohamy Aly , Cappato Riccardo
Published: August 2024

Background: Despite the progressive course of atrial fibrillation (AF), the optimal timing of radiofrequency catheter ablation (RFCA) during disease course is still unknown. We aimed to investigate the impact of early RFCA within a year after AF diagnosis on procedural outcomes. Methods: A single-center retrospective study was conducted on symptomatic AF patients (n = 130) referred for RFCA with a 16-month median follow-up. Patients were stratified based on the diagnosis-to-ablation time (DAT) into early (≤1 year) and late (>1 year) RFCA groups. Atrial arrhythmia recurrence after single RFCA was the primary outcome. Secondary outcomes included cardiovascular hospitalizations, AF progression, and antiarrhythmic drug (AAD) use. Results: Within a year of AF diagnosis, 33 patients (25.4%) underwent RFCA. In the early-RFCA group, 84.4% of patients did not have recurrent atrial arrhythmia, in contrast to 60.8% in the late-RFCA group (p = 0.039). Late RFCA (HR = 2.74, 95% CI = 1.062–7.052, p = 0.037) and AF recurrence during the blanking period (HR = 4.57, 95% CI = 2.38–8.57, p < 0.0001) were independent predictors of atrial arrhythmia recurrence on multivariate analysis. Compared to the late-RFCA group, the early-RFCA group had significantly lower rates of cardiovascular hospitalizations (18% vs. 42%, p = 0.023), AF progression (0.0% vs. 11.3%, p = 0.044), and AAD use (45.4% vs. 81.4%, p < 0.001). Conclusions: Early RFCA within a year of AF diagnosis is associated with less atrial arrhythmia recurrence, fewer cardiovascular hospitalizations, less AF progression, and less AAD use. DAT of more than one year and AF recurrence during the blanking period are independent predictors of atrial arrhythmia recurrence after single RFCA.
The Moderating Effect of Suggestibility on the Relationship between Body Mass Index and Body Dissatisfaction in Women
Authors: Meschberger-Annweiler Franck-Alexandre , Ascione Mariarca , Porras-Garcia Bruno , Mendoza-Medialdea Maria Teresa , Ferrer-Garcia Marta , Gutierrez-Maldonado Jose
Published: August 2024

Background: Body dissatisfaction (BD) has been consistently linked to adverse consequences on mental health and overall well-being, and is recognized as a significant contributing factor in the initiation and persistence of eating disorders (EDs). Empirical evidence has demonstrated that an elevated body mass index (BMI) and media influence and pressure about a thin ideal heighten the risk of subsequent BD. Moreover, suggestibility, a propensity to accept and act upon messages without critical evaluation, has been shown to be positively associated with greater susceptibility to the influence of sociocultural messages that endorse the thin ideal. This study aimed to assess whether suggestibility moderates the association between BMI and BD in women. Methods: A total of 117 women completed assessments using the Eating Disorder Inventory-3 (EDI-3) BD subscale and the Suggestibility Inventory, which encompasses a general suggestibility index and a subscale that evaluates susceptibility to influence by others. We conducted moderation analyses employing the PROCESS macro, with BMI as the central predictor, BD as the outcome variable, and suggestibility and its subscale as moderators. Results: The findings revealed statistically significant positive moderating interactions for both the general suggestibility index and susceptibility to influence by others. Specifically, women who exhibited high levels of suggestibility and susceptibility to influence by others demonstrated a more pronounced increase in BD as their BMI increased. Conclusions: These outcomes are in line with the sociocultural model of EDs, suggesting that greater susceptibility to external influences amplifies the impact of societal pressures to conform to thin ideals.
Reliability of the Biomechanical Assessment of the Sagittal Lumbar Spine and Pelvis on Radiographs Used in Clinical Practice: A Systematic Review of the Literature
Authors: Betz Joseph W. , Lightstone Douglas F. , Oakley Paul A. , Haas Jason W. , Moustafa Ibrahim M. , Harrison Deed E.
Published: August 2024

Background: Biomechanical analysis of the sagittal alignment of the lumbar spine and pelvis on radiographs is common in clinical practices including chiropractic, physical therapy, scoliosis-related thoraco-lumbo-sacral orthosis (TLSO) management, orthopedics, and neurosurgery. Of specific interest is the assessment of pelvic morphology and the relationship between angle of pelvic incidence, sacral slope, and lumbar lordosis to pain, disability, and clinical treatment of spine conditions. The current state of the literature on the reliability of common methods quantifying these parameters on radiographs is limited. Methods: The objective of this systematic review is to identify and review the available studies on the reliability of different methods of biomechanical analysis of sagittal lumbo-pelvic parameters used in clinical practice. Our review followed the recommendations of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The design of this systematic review was registered with PROSPERO (CRD42023379873). Results: The search strategy yielded a total of 2387 articles. A total of 1539 articles were screened after deduplication and exclusion by automation tools, leaving 473 full-text articles that were retrieved. After exclusion, 64 articles met the inclusion criteria. The preponderance of the evidence showed good to excellent reliability for biomechanical assessment of sagittal lumbo-pelvic spine alignment. Conclusions: The results of this systematic review of the literature show that sagittal radiographic analysis of spinal biomechanics and alignment of the human lumbo-pelvic spine is a reliable tool for aiding diagnosis and management in clinical settings.
Measurement of Cardiothoracic Ratio on Chest X-rays Using Artificial Intelligence—A Systematic Review and Meta-Analysis
Authors: Kufel Jakub , Czogalik Łukasz , Bielówka Michał , Magiera Mikołaj , Mitręga Adam , Dudek Piotr , Bargieł-Łączek Katarzyna , Stencel Magdalena , Bartnikowska Wiktoria , Mielcarska Sylwia , Modlińska Sandra , Nawrat Zbigniew , Cebula Maciej , Gruszczyńska Katarzyna
Published: August 2024

Background: Chest X-rays (CXRs) are pivotal in clinical diagnostics, particularly in assessing cardiomegaly through the cardiothoracic ratio (CTR). This systematic review and meta-analysis evaluate the efficacy of artificial intelligence (AI) in automating CTR determination to enhance patient care and streamline diagnostic processes. They are concentrated on comparing the performance of AI models in determining the CTR against human assessments, identifying the most effective models for potential clinical implementation. This study was registered with PROSPERO (no. CRD42023437459). No funding was received. Methods: A comprehensive search of medical databases was conducted in June 2023. The search strategy adhered to the PICO framework. Inclusion criteria encompassed original articles from the last decade focusing on AI-assisted CTR assessment from standing-position CXRs. Exclusion criteria included systematic reviews, meta-analyses, conference abstracts, paediatric studies, non-original articles, and studies using imaging techniques other than X-rays. After initial screening, 117 articles were reviewed, with 14 studies meeting the final inclusion criteria. Data extraction was performed by three independent investigators, and quality assessment followed PRISMA 2020 guidelines, using tools such as the JBI Checklist, AMSTAR 2, and CASP Diagnostic Study Checklist. Risk of bias was assessed according to the Cochrane Handbook guidelines. Results: Fourteen studies, comprising a total of 70,472 CXR images, met the inclusion criteria. Various AI models were evaluated, with differences in dataset characteristics and AI technology used. Common preprocessing techniques included resizing and normalization. The pooled AUC for cardiomegaly detection was 0.959 (95% CI 0.944–0.975). The pooled standardized mean difference for CTR measurement was 0.0353 (95% CI 0.147–0.0760). Significant heterogeneity was found between studies (I2 89.97%, p < 0.0001), with no publication bias detected. Conclusions: Standardizing methodologies is crucial to avoid interpretational errors and advance AI in medical imaging diagnostics. Uniform reporting standards are essential for the further development of AI in CTR measurement and broader medical imaging applications.
Introduction to the Special Issue “Personality and Individual Differences”
Authors: Brauer Kay , Proyer René T.
Published: August 2024

The study of intelligence is one of the foundations of scientific psychology, and for more than a century, researchers from psychology and other disciplines such as neuroscience, genetics, and education have been interested in extending the knowledge about the structure and correlates of intelligence [...]
An OOSEM-Based Design Pattern for the Development of AUV Controllers
Authors: Sang Cao Duc , He Ngo Van , Hien Ngo Van , Khuyen Nguyen Trong
Published: August 2024

This article introduces a new design pattern that provides an optimal solution for the systematic development of AUV controllers. In this study, a hybrid control model is designed on the basis of the OOSEM (Object-Oriented Systems Engineering Method), combined with MDA (Model-Driven Architecture) concepts, real-time UML/SysML (Unified Modeling Language/Systems Modeling Language), and the UKF (unscented Kalman filter) algorithm. This hybrid model enables the implementation of the control elements of autonomous underwater vehicles (AUVs), which are considered HDSs (hybrid dynamic systems), and it can be adapted for reuse for most standard AUV platforms. To achieve this goal, a dynamic AUV model is integrated with the specializations of the OOSEM/MDA, in which an analysis model is clarified via a use-case model definition and then combined with HA (hybrid automata) to precisely define the control requirements. Next, the designed model is tailored via real-time UML/SysML to obtain the core control blocks, which describe the behaviors and structures of the control parts in detail. This design model is then transformed into an implementation model with the assistance of round-trip engineering to conveniently realize a controller for AUVs. Based on this new model, a feasible AUV controller for low-cost, turtle-shaped AUVs is implemented, and it is utilized to perform planar trajectory tracking.