bluuebunny/crossref_metadata_2025 huggingface dataset:
Chicken Secondary Lymphoid Tissues—Structure and Relevance in Immunological Research
Authors: Ceccopieri Cassandra , Madej Jan P.
Published: August 2024

Recent discoveries have indicated the importance of developing modern strategies for vaccinations, more ethical research models, and effective alternatives to antibiotic treatment in farm animals. Chickens (Gallus gallus) play a crucial role in this context given the commercial and economic relevance of poultry production worldwide and the search for analogies between the immune systems of humans and birds. Specifically, chicken secondary lymphoid tissues share similar features to their human counterparts. Chickens have several secondary or peripheral lymphoid tissues that are the sites where the adaptive immune response is initiated. The more general classification of these organs divides them into the spleen and skin-, pineal-, or mucosa-associated lymphoid tissues. Each of these tissues is further subdivided into separate lymphoid structures that perform specific and different functions along the animal’s body. A review summarizing the state of the art of research on chicken secondary lymphoid organs is of great relevance for the design of future studies.
Identification of Aeromonas veronii as the Pathogen Associated with Massive Mortality in Bronze Gudgeon (Coreius heterodon)
Authors: Liu Wenzhi , Li Mengmeng , Xue Mingyang , Zhou Yong , Jiang Nan , Meng Yan , Liu Yisha , Jiang Jingwen , Liao Xiaolin , Fan Yuding
Published: August 2024

Aeromonas veronii, an opportunistic pathogen toward aquatic organisms, was identified as the causative pathogen (isolate WH10) in diseased bronze gudgeon via bacterial isolation, and morphological, physiological, biochemical, and molecular characterization. WH10 exerted its pathogenicity via five virulence genes, including those encoding cytotoxic enterotoxins (act and alt), lipase (lip), a quorum sensing-controlled virulence factor (LuxS), and a Type III secretion system inner membrane component (ascV). WH10 was shown to be sensitive to compound sulfamethoxazoles, cefothiophene, doxycycline, and sulfamethoxazole. Toward bronze gudgeon, WH10 had a median lethal dose (LD50) of 1.36 × 106 colony forming units/mL. Analysis of blood parameters of diseased fish revealed significant increases in monocytes and neutrophils, but decreased numbers of lymphocytes. Serum aspartate aminotransferase activity and triglyceride concentration were significantly higher in diseased fish than in healthy fish. The reverse was noted for alkaline phosphatase, total protein, albumin, total cholesterol, and glucose. Thus, Aeromonas veronii is implicated as the causative agent of the mass mortality observed in bronze gudgeon, warranting further investigations into the diagnosis, epidemiology, prevention, and treatment of this infectious disease.
CMAH Coding Sequence Variants in 15 Non-Domestic Felid Species Related to ABC Blood Group System
Authors: Kehl Alexandra , Kuder Henrike , Parkinson Lily , Koenig Amie , Langbein-Detsch Ines , Mueller Elisabeth , Giger Urs
Published: August 2024

Different blood group systems have been characterized in people and other mammals. In domestic cats, the ABC blood group system plays the most important clinical role and has been investigated extensively—from the phenotype to the molecular genetics. In non-domestic felids, phenotypic ABC blood typing has been performed by different methods to detect the antigens, but the four informative CMAH markers in domestic cats were not able to identify types B and C (AB) in non-domestic cats. In this study, 138 blood samples from 15 non-domestic (wild) felid species were investigated by CMAH exonic sequencing and genotyping for putative variants causing type B or C (AB) and correlation to the respective ABC blood phenotype. A total of 58 CMAH variants were found, including 15 missense and 43 synonymous CMAH variants. One variant (c.635G>C) was concordant with blood type B (and C) in cheetahs and type B in cougars, compared to blood type A in all other felid species (lion, tiger, Canada lynx, snow leopard, clouded leopard, serval, jaguar, fishing cat, Pallas cat, bobcat, black footed cat, leopard, and sand cat). Since cheetahs and cougars belong to the genera puma, it could not be determined if the common CMAH variant is either a marker for type B (or C) or is just common in pumas.
Behavioural Responses of Beef Cattle to Hot Conditions
Authors: Idris Musadiq , Sullivan Megan , Gaughan John B. , Phillips Clive J. C.
Published: August 2024

Cattle are increasingly exposed to hot temperatures as a result of climate change, and a better understanding of behavioural responses could be beneficial for the diagnosis of heat loads. The changes in the positioning of key body parts, feeding behaviour, body maintenance, and respiratory dynamics were assessed in 24 Black Angus steers individually exposed to hot conditions and fed a finisher diet based on cereal grain or a substituted diet (8% of the grain replaced by an isoenergetic amount of lucerne hay). Increased respiration rate during the heat load period, compared to the recovery period, was associated with increased stepping, especially by left limbs. Cattle also reduced eating, grooming, and scratching during the heat load period. The lowered head, backward ear, vertical or raised tail, and increased respiration rate and panting persisted in cattle during the heat load period. Cattle on the cereal grain diet stood for longer and were more likely to hold their ears backward and tail vertical than those on the substituted diet. We conclude that these behaviours could be used to detect animals that are most affected and that changing from a cereal-based diet to a substituted diet containing a higher amount of fibre, such as lucerne hay, can reduce hyperthermic behavioural responses to a heat load.
Revealing the Mechanism of Esculin in Treating Renal Cell Carcinoma Based on Network Pharmacology and Experimental Validation
Authors: Chen Zixuan , Wang Cunzhou , Cai Yuesong , Xu An , Han Chengtao , Tong Yanjun , Cheng Sheng , Liu Min
Published: August 2024

Purpose: This study aims to explore the potential mechanisms of esculin in the treatment of renal cell carcinoma (RCC). Methods: We employed network pharmacology to predict the potential mechanisms and targets of esculin in RCC. Molecular docking techniques were then employed to validate the predicted targets. Additionally, a series of in vitro experiments were conducted to verify the anticancer effects of esculin on RCC cells, including the CCK-8 assay, EdU assay, wound healing assay, apoptosis assay, and Western blot. Results: Network pharmacology and molecular docking results identified GAPDH, TNF, GSK3B, CCND1, MCL1, IL2, and CDK2 as core targets. GO and KEGG analyses suggested that esculin may influence apoptotic processes and target the PI3K/Akt pathway in RCC. Furthermore, the CCK-8 assay demonstrated that esculin inhibited RCC cell viability. Microscopic observations revealed that following esculin treatment, there was an increase in cell crumpling, a reduction in cell density, and an accumulation of floating dead cells. Additionally, with increasing esculin concentrations, the proportion of EdU-positive cells decreased, the wound closure ratio decreased, the proportion of PI-positive cells increased, the expression levels of BAX and cleaved-caspase-3 proteins increased, and the expression level of Bcl2 protein decreased. These findings suggested that esculin inhibits the proliferation and migration of RCC cells while promoting apoptosis. Moreover, esculin was found to target GAPDH and inhibit the PI3K/Akt pathway. Conclusions: This study is the first to elucidate the therapeutic effects of esculin on RCC cells. The results provide evidence supporting the clinical application of esculin and introduce a promising new candidate for RCC treatment.
Ultrasoft Long-Lasting Reusable Hydrogel-Based Sensor Patch for Biosignal Recording
Authors: Tessier Alexandre , Zhuo Shuyun , Kabiri Ameri Shideh
Published: August 2024

Here, we report an ultrasoft extra long-lasting, reusable hydrogel-based sensor that enables high-quality electrophysiological recording with low-motion artifacts. The developed sensor can be used and stored in an ambient environment for months before being reused. The developed sensor is made of a self-adhesive electrical-conductivity-enhanced ultrasoft hydrogel mounted in an Ecoflex-based frame. The hydrogel’s conductivity was enhanced by incorporating polypyrrole (PPy), resulting in a conductivity of 0.25 S m−1. Young’s modulus of the sensor is only 12.9 kPa, and it is stretchable up to 190%. The sensor was successfully used for electrocardiography (ECG) and electromyography (EMG). Our results indicate that using the developed hydrogel-based sensor, the signal-to-noise ratio of recorded electrophysiological signals was improved in comparison to that when medical-grade silver/silver chloride (Ag/AgCl) wet gel electrodes were used (33.55 dB in comparison to 22.16 dB). Due to the ultra-softness, high stretchability, and self-adhesion of the developed sensor, it can conform to the skin and, therefore, shows low susceptibility to motion. In addition, the sensor shows no sign of irritation or allergic reaction, which usually occurs after long-term wearing of medical-grade Ag/AgCl wet gel electrodes on the skin. Further, the sensor is fabricated using a low-cost and scalable fabrication process.
MLS-Net: An Automatic Sleep Stage Classifier Utilizing Multimodal Physiological Signals in Mice
Authors: Jiang Chengyong , Xie Wenbin , Zheng Jiadong , Yan Biao , Luo Junwen , Zhang Jiayi
Published: August 2024

Over the past decades, feature-based statistical machine learning and deep neural networks have been extensively utilized for automatic sleep stage classification (ASSC). Feature-based approaches offer clear insights into sleep characteristics and require low computational power but often fail to capture the spatial–temporal context of the data. In contrast, deep neural networks can process raw sleep signals directly and deliver superior performance. However, their overfitting, inconsistent accuracy, and computational cost were the primary drawbacks that limited their end-user acceptance. To address these challenges, we developed a novel neural network model, MLS-Net, which integrates the strengths of neural networks and feature extraction for automated sleep staging in mice. MLS-Net leverages temporal and spectral features from multimodal signals, such as EEG, EMG, and eye movements (EMs), as inputs and incorporates a bidirectional Long Short-Term Memory (bi-LSTM) to effectively capture the spatial–temporal nonlinear characteristics inherent in sleep signals. Our studies demonstrate that MLS-Net achieves an overall classification accuracy of 90.4% and REM state precision of 91.1%, sensitivity of 84.7%, and an F1-Score of 87.5% in mice, outperforming other neural network and feature-based algorithms in our multimodal dataset.
Research on the Mechanism and Application of High Pre-Tension on the Crack-Arresting Effect of Rockbolt Anchorage
Authors: Wu Bowen , Chang Jucai , Wang Xiangyu , Shi Wenbao , Li Chuanming , Chen Dingchao
Published: August 2024

In order to investigate the effect of pre-tension on the anchoring and crack-arresting effect of rockbolts, a theoretical model of stress intensity factor at the crack tip in anchored surrounding rock was established using fracture mechanics theory. An expression for the difference in stress intensity factor due to axial force on the rockbolt was derived, exploring the influence of pre-tension on the stress intensity factor of cracks. A numerical model of anchored crack specimens was developed using UDEC (V6.0) software to simulate and analyze the mechanical performance and damage characteristics of specimens anchored with different pre-tension. The results indicate that the difference in stress intensity factor of cracks is positively correlated with pre-tension. High-pre-tensioned rockbolts can effectively reduce the stress intensity factor of cracks. Prestressed rockbolts can alter the failure mode of rock masses from shear failure along pre-existing cracks to tensile splitting failure. The application of high pre-tension significantly enhances the strength of the rock mass, reducing both the damage degree and the number of internal cracks. After anchoring with high-pre-tensioned rockbolts, the peak strength and elastic modulus of the crack specimens increased by 22.5% and 31.9%, respectively, while damage degree decreased by 17.4%, the number of shear cracks decreased by 22.6%, and the number of tensile cracks decreased by 42.9%. The pre-tensioned rockbolt method proposed in this study was applied to the support of roadway widening. Field monitoring data indicated that the axial force of the rockbolts in the test section generally exceeded 60 kN, effectively controlling the deformation of the roadway surrounding the rock. The convergence of the two sides decreased by 22%, and borehole inspections showed a significant reduction in internal cracks. The research results provide a theoretical basis for controlling the discontinuous deformation of deep broken surrounding rock roadways.
Seismic Performance of Precast Steel Beam-Column Joint with Bolted Connection
Authors: Chen Yandan , Lu Yonggang , Liu Tong
Published: August 2024

This paper introduces a modular, assembled steel beam-column flange connection joint that efficiently connects prefabricated beams and columns using high-strength bolts. It enables the rapid repair of damaged joints after earthquakes by replacing flange connectors and high-strength bolt groups. Four joint specimens with varying thicknesses and lengths of the inner flange sleeve, scaled at a 1:2 ratio, were fabricated to evaluate performance. These specimens were subjected to low circumferential reciprocal loads to investigate damage modes, hysteresis curves, skeleton curves, ductility performance, energy dissipation capacity, and seismic performance, including stiffness degradation. The test and analysis results reveal that the primary failure mode is characterized by bulging of the flange jacket cover, with damage concentrated in the plastic hinge zone at the beam end. The flange connection joint exhibits excellent load-bearing, rotational, and energy dissipation capacities. The ‘secondary strengthening’ feature significantly enhances joint load-bearing capacity, ductility performance, and energy dissipation, increasing overall safety redundancy. Increasing the thickness and length of the flange connector substantially improves seismic performance and enlarges the plastic development area.
Lighting in Buildings
Authors: Durmus Dorukalp , Hu Wenye , Doulos Lambros T.
Published: August 2024

Lighting in the built environment has evolved since the rapid uptake of solid-state lighting (SSL) devices [...]
Tumor-Infiltrating Lymphocyte Scoring in Neoadjuvant-Treated Breast Cancer
Authors: Thomas Noémie , Garaud Soizic , Langouo Mireille , Sofronii Doïna , Boisson Anaïs , De Wind Alexandre , Duwel Valérie , Craciun Ligia , Larsimont Dennis , Awada Ahmad , Willard-Gallo Karen
Published: August 2024

Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO® image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous.
Long-Term Outcomes of Childhood Acute Lymphocytic Leukemia Treated with Adapted Berlin–Frankfurt–Münster (BFM) Protocols: A Multicentric Analysis from a Developing Country
Authors: Horn Patricia Regina Cavalcanti Barbosa , Ribeiro-Carvalho Marilza de Moura , Azevedo Alice Maria Boulhosa de , Sousa Adriana Martins de , Faria Simone , Wiggers Cristina , Rouxinol Soraia , Schramm Marcia Trindade , Sanches Bárbara Sarni , Duarte Nathalia Lopez , Seixas Teresa de Souza Fernandez , Gomes Bernadete Evangelho , Oliveira Elen de , Arcuri Leonardo Javier , Costa Elaine Sobral da , Land Marcelo Gerardin Poirot , Souza Maria Helena Faria Ornellas de
Published: August 2024

Introduction: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin–Frankfurt–Münster (BFM) protocols and compare our results with the original BFM reports. Methods: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997–2007 and 2008–2018 cohorts were analyzed separately. Results: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997–2007 period, respectively, 88% and 80% (BFM standard risk group—SRG), 75% and 67% (intermediate risk group—IRG), and 48% and 33% (high-risk group—HRG). The corresponding numbers for the 2008–2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. Conclusion: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.
Small Bowel Cancer in Crohn’s Disease
Authors: Faggiani Ilaria , D’Amico Ferdinando , Furfaro Federica , Zilli Alessandra , Parigi Tommaso Lorenzo , Cicerone Clelia , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio , Allocca Mariangela
Published: August 2024

Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that frequently affects the small bowel. Individuals diagnosed with CD are at increased risk of developing bowel cancer compared to the general population. Small bowel cancer is a rare but significant CD complication. Adenocarcinoma represents the most prevalent of these neoplasms, followed by neuroendocrine tumors and sarcomas. The primary risk factors identified are being of the male sex, disease duration, previous surgical intervention, perianal disease, and chronic inflammation. The precise etiology remains unclear. Another crucial issue concerns the role of immunomodulators and advanced therapies. By inhibiting inflammation, these therapies can reduce the risk of cancer, which is often initiated by the inflammation–dysplasia–adenocarcinoma sequence. In accordance with the most recent guidelines, it is not necessary to conduct surveillance in patients with small bowel cancer among CD patients, as it is considered a rare disease. Nevertheless, it is of significant importance for gastroenterologists to be aware of this potential CD complication, as well as the patients who are most at risk of developing it. The purpose of this review is to provide a comprehensive overview of CD-SBC, focusing on epidemiology, etiopathogenesis, risk factors, diagnosis, and the role of advanced therapies in CD-SBC.
Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio: Side by Side with Molecular Mutations in Patients with Non-Small Cell Lung Cancer—The INOLUNG Study
Authors: Budin Corina Eugenia , Cocuz Iuliu Gabriel , Enache Liviu Sorin , Rența Ionuț Alexandru , Cazacu Cristian , Pătrîntașu Dariana Elena , Olteanu Mihai , Râjnoveanu Ruxandra-Mioara , Ianoși Edith Simona , Râjnoveanu Armand , Cotoi Ovidiu Simion
Published: August 2024

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The parameters analyzed included histopathological type (NSCLC: squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters, and associated comorbidities. Results: A total of 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5.30 versus 2.60, p < 0.001; 217 versus 136, p < 0.001, respectively). NLR and PLR differ between men and women (p = 0.005 and p = 0.056, respectively). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusions: The NLR and PLR values may serve as new predictive biomarkers for the diagnosis of disease in patients with lung cancer, especially those with NSCLC.
Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation: An 18-Year Experience at a Tertiary Center in Kuwait
Authors: Ali Rola H. , Alsaber Ahmad R. , Mohanty Asit K. , Alnajjar Abdulsalam , Mohammed Eiman M. A. , Alateeqi Mona , Jama Hiba , Almarzooq Ammar , Benobaid Noelle , Alqallaf Zainab , Ahmed Amir A. , Bahzad Shakir , Alkandari Mohammad
Published: August 2024

In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p = 0.018), with mitosis ≤5/5 mm2, and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.
WFUMB Review Paper. Incidental Findings in Otherwise Healthy Subjects, How to Manage: Liver
Authors: Șirli Roxana , Popescu Alina , Jenssen Christian , Möller Kathleen , Lim Adrian , Dong Yi , Sporea Ioan , Nürnberg Dieter , Petry Marieke , Dietrich Christoph F.
Published: August 2024

An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed.
The Efficacy of Cannabis in Oncology Patient Care and Its Anti-Tumor Effects
Authors: Shalata Walid , Abu Saleh Omar , Tourkey Lena , Shalata Sondos , Neime Ala Eddin , Abu Juma’a Ali , Soklakova Arina , Tourkey Lama , Jama Ashraf Abu , Yakobson Alexander
Published: August 2024

As the legalization of medical cannabis expands across several countries, interest in its potential advantages among cancer patients and caregivers is burgeoning. However, patients seeking to integrate cannabis into their treatment often encounter frustration when their oncologists lack adequate information to offer guidance. This knowledge gap is exacerbated by the scarcity of published literature on the benefits of medical cannabis, leaving oncologists reliant on evidence-based data disheartened. This comprehensive narrative article, tailored for both clinicians and patients, endeavors to bridge these informational voids. It synthesizes cannabis history, pharmacology, and physiology and focuses on addressing various symptoms prevalent in cancer care, including insomnia, nausea and vomiting, appetite issues, pain management, and potential anti-cancer effects. Furthermore, by delving into the potential mechanisms of action and exploring their relevance in cancer treatment, this article aims to shed light on the potential benefits and effects of cannabis in oncology.
Paracrine Activation of STAT3 Drives GM-CSF Expression in Breast Carcinoma Cells, Generating a Symbiotic Signaling Network with Breast Carcinoma-Associated Fibroblasts
Authors: Osuala Kingsley O. , Chalasani Anita , Aggarwal Neha , Ji Kyungmin , Moin Kamiar
Published: August 2024

This study evaluated the paracrine signaling between breast carcinoma-associated fibroblasts (CAFs) and breast cancer (BCa) cells. Resolving cell–cell communication in the BCa tumor microenvironment (TME) will aid the development of new therapeutics. Here, we utilized our patented TAME (tissue architecture and microenvironment engineering) 3D culture microphysiological system, which is a suitable pathomimetic avatar for the study of the BCa TME. We cultured in 3D BCa cells and CAFs either alone or together in cocultures and found that when cocultured, CAFs enhanced the invasive characteristics of tumor cells, as shown by increased proliferation and spread of tumor cells into the surrounding matrix. Secretome analysis from 3D cultures revealed a relatively high secretion of IL-6 by CAFs. A marked increase in the secretion of granulocyte macrophage-colony stimulating factor (GM-CSF) when carcinoma cells and CAFs were in coculture was also observed. We theorized that the CAF-secreted IL-6 functions in a paracrine manner to induce GM-CSF expression and secretion from carcinoma cells. This was confirmed by evaluating the activation of STAT3 and gene expression of GM-CSF in carcinoma cells exposed to CAF-conditioned media (CAF-CM). In addition, the treatment of CAFs with BCa cell-CM yielded a brief upregulation of GM-CSF followed by a marked decrease, indicating a tightly regulated control of GM-CSF in CAFs. Secretion of IL-6 from CAFs drives the activation of STAT3 in BCa cells, which in turn drives the expression and secretion of GM-CSF. As a result, CAFs exposed to BCa cell-secreted GM-CSF upregulate inflammation-associated genes such as IL-6, IL-6R and IL-8, thereby forming a positive feedback loop. We propose that the tight regulation of GM-CSF in CAFs may be a novel regulatory pathway to target for disrupting the CAF:BCa cell symbiotic relationship. These data provide yet another piece of the cell–cell communication network governing the BCa TME.
Comparative Analysis of AML Classification Systems: Evaluating the WHO, ICC, and ELN Frameworks and Their Distinctions
Authors: Salman Huda
Published: August 2024

Comprehensive analyses of the molecular heterogeneity of acute myelogenous leukemia, AML, particularly when malignant cells retain normal karyotype, has significantly evolved. In 2022, significant revisions were introduced in the World Health Organization (WHO) classification and the European LeukemiaNet (ELN) 2022 guidelines of acute myeloid leukemia (AML). These revisions coincided with the inception of the first version of the International Consensus Classification (ICC) for AML. These modifications aim to improve diagnosis and treatment outcomes via a comprehensive incorporation of sophisticated genetic and clinical parameters as well as facilitate accruals to innovative clinical trials. Key updates include modifications to the blast count criteria for AML diagnosis, with WHO 2022 eliminating the ≥20% blast requirement in the presence of AML-defining abnormalities and ICC 2022 setting a 10% cutoff for recurrent genetic abnormalities. Additionally, new categories, such as AML with mutated TP53 and MDS/AML, were introduced. ELN 2022 guidelines retained risk stratification approach and emphasized the critical role of measurable residual disease (MRD) that increased the use of next-generation sequencing (NGS) and flow cytometry testing. These revisions underscore the importance of precise classification for targeted treatment strategies and improved patient outcomes. How much difference versus concordance these classifications present and the impact of those on clinical practice is a continuing discussion.
Discrepancies between the Spatial Distribution of Cancer Incidence and Mortality as an Indicator of Unmet Needs in Cancer Prevention and/or Treatment in Hungary
Authors: Ádány Róza , Juhász Attila , Nagy Csilla , Burkali Bernadett , Pikó Péter , McKee Martin , Oroszi Beatrix
Published: August 2024

There is a rich body of literature on the distribution of cancer incidence and mortality in socioeconomically different world regions, but none of the studies has compared the spatial distribution of mortality and incidence to see if they are consistent with each other. All malignant neoplasms combined and cervical, colorectal, breast, pancreatic, lung, and oral cancers separately were studied in the Hungarian population aged 25–64 years for 2007–2018 at the municipality level by sex. In each case, the spatial distribution of incidence and mortality were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis, and spatial scan statistics. A positive association between deprivation and mortality was found for each type of cancer, but there was no significant association for male colorectal cancer (relative risk (RR) 1.00; 95% credible interval (CI) 0.99–1.02), pancreatic cancer (RR: 1.01; 95%CI 0.98–1.04), and female colorectal cancer incidence (RR: 1.01; 95%CI 0.99–1.03), whereas a negative association for breast cancer (RR: 0.98; 95%CI 0.96–0.99) was found. Disease mapping analyses showed only partial overlap between areas of high incidence and mortality, often independent of deprivation. Our results highlight not only the diverse relationship between cancer burden and deprivation, but also the inconsistent relationship between cancer incidence and mortality, pointing to areas with populations that require special public health attention.
Long Non-Coding RNAs, Nuclear Receptors and Their Cross-Talks in Cancer—Implications and Perspectives
Authors: Tiwari Prabha , Tripathi Lokesh P.
Published: August 2024

Long non-coding RNAs (lncRNAs) play key roles in various epigenetic and post-transcriptional events in the cell, thereby significantly influencing cellular processes including gene expression, development and diseases such as cancer. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that typically regulate transcription of genes involved in a broad spectrum of cellular processes, immune responses and in many diseases including cancer. Owing to their many overlapping roles as modulators of gene expression, the paths traversed by lncRNA and NR-mediated signaling often cross each other; these lncRNA-NR cross-talks are being increasingly recognized as important players in many cellular processes and diseases such as cancer. Here, we review the individual roles of lncRNAs and NRs, especially growth factor modulated receptors such as androgen receptors (ARs), in various types of cancers and how the cross-talks between lncRNAs and NRs are involved in cancer progression and metastasis. We discuss the challenges involved in characterizing lncRNA-NR associations and how to overcome them. Furthering our understanding of the mechanisms of lncRNA-NR associations is crucial to realizing their potential as prognostic features, diagnostic biomarkers and therapeutic targets in cancer biology.
Impact of Neuroendocrine Differentiation (NED) on Enzalutamide and Abiraterone Efficacy in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Retrospective Analysis
Authors: Farinea Giovanni , Calabrese Mariangela , Carfì Federica , Saporita Isabella , Poletto Stefano , Delcuratolo Marco Donatello , Turco Fabio , Audisio Marco , Di Stefano Francesco Rosario , Tucci Marcello , Buttigliero Consuelo
Published: August 2024

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC patients treated with ARPIs. Methods: We retrospectively analyzed 327 mCRPC patient data treated with Enzalutamide or Abiraterone in the first and second or successive lines of treatment. NED was assessed using prostate biopsy samples through immunohistochemical staining. Results: NED was confirmed in 32/327 (9.8%) mCRPC patients. In the overall population, mCRPC with NED showed worse PFS (4.38 vs. 11.48 months HR 2.505 [1.71–3.68] p < 0.05), disease control rate (DCR), and PSA response. In the first line setting, mCRPC with NED demonstrated worse PFS (8.5 vs. 14.9 months HR 2.13 [1.18–3.88], p < 0.05). Similarly, in the second or successive lines, mCRPC with NED showed worse PFS (4.0 vs. 7.5 months HR 2.43 [1.45–4.05] p < 0.05), DCR, PSA response and OS (12.53 vs. 18.03 months HR 1.86 [1.12–3.10] p < 0.05). The adverse impact of NED on PFS was consistence across all subgroups; we also noted a trend of worse PFS in patients with high vs. low NED. Conclusions: In our study, mCRPC with NED treated with Enzalutamide or Abiraterone showed worse clinical outcomes. NED assessment should be considered to optimize treatment decisions in the mCRPC setting.
New Insights into D-Aspartate Signaling in Testicular Activity
Authors: Falvo Sara , Santillo Alessandra , Di Fiore Maria Maddalena , Venditti Massimo , Grillo Giulia , Latino Debora , Baccari Isabella , Petito Giuseppe , Chieffi Baccari Gabriella
Published: August 2024

D-aspartate (D-Asp) is an amino acid found in high concentrations in the testis and pituitary gland. Increasing evidence suggests that D-Asp promotes spermatogenesis by activating testosterone production in the Leydig cells via LH release from the pituitary gland. In vitro studies indicate that D-Asp may also influence steroidogenesis and spermatogenesis through autocrine and paracrine signals. D-Asp enhances StAR and steroidogenic enzyme expressions, facilitating testicular cell proliferation via the GluR/ERK1/2 pathway. Moreover, it supports spermatogenesis by enhancing the mitochondrial function in spermatocytes, aiding in the metabolic shift during meiosis. Enhanced mitochondrial function, along with improved MAM stability and reduced ER stress, has been observed in Leydig and Sertoli cells treated with D-Asp, indicating potential benefits in steroidogenesis and spermatogenesis efficiency. Conversely, D-Asp exerts a notable anti-apoptotic effect in the testis via the AMPAR/AKT pathway, potentially mediated by antioxidant enzyme modulation to mitigate testicular oxidative stress. This review lays the groundwork for future investigations into the molecules promoting spermatogenesis by stimulating endogenous testosterone biosynthesis, with D-amino acids emerging as promising candidates.
Effect of Chloride Salt Erosion on the Properties of Straw Fiber Reactive Powder Concrete
Authors: Wang Hangyang , Gong Kaiwei , Cheng Bingling , Peng Xi , Wang Hui , Xu Bin
Published: August 2024

Straw fibers are renowned for their cost-effectiveness, sustainability, and durability. They represent a promising natural reinforcement option for reactive powder concrete (RPC). This paper investigated the impact of straw fibers on RPC’s workability, mechanical performance (mechanical strength and flexural toughness), and electrical properties (electrical resistance and AC impedance spectroscopy curves). The straw fiber volumes ranged from 1% to 4.0% of the total RPC volume. Specimens were cured under standard curing conditions for 3, 7, 14, and 28 days. Mechanical and electrical properties of the specimens were tested before chloride salt erosion. The mass loss and ultrasonic velocity loss of the samples were measured under NaCl freeze–thaw cycles (F-Cs). The mass loss, ultrasonic velocity loss, and mechanical strengths loss of the samples were measured under NaCl dry–wet alternations (D-As). The findings indicated that incorporating straw fibers enhanced RPC’s flexural strength, compressive strength, and flexural toughness by 21.3% to 45.76%, −7.16% to 11.62%, and 2.4% to 32.7%, respectively, following a 28-day curing period. The addition of straw fibers could augment the AC electrical resistance of the RPC by 10.17% to 58.1%. The electrical characteristics of the RPC adhered to series conduction models. A power function relationship existed between the electrical resistance and mechanical strengths of the RPC. After 10 NaCl D-As, the mass loss rate, ultrasonic velocity loss rate, flexural strength, and compressive strength loss rates of the RPC decreased by 0.42% to 1.68%, 2.69% to 6.73%, 9.6% to 35.65%, and 5.41% to 34.88%, respectively, compared to blank samples. After undergoing 200 NaCl F-Cs, the rates of mass loss and ultrasonic velocity loss of the RPC decreased by 0.89% to 1.01% and 6.68% to 8.9%, respectively.
Whole-Body SPECT/CT: Protocol Variation and Technical Consideration—A Narrative Review
Authors: Alqahtani Mansour M.
Published: August 2024

Introducing a hybrid imaging approach, such as single-photon emission computerized tomography with X-ray computed tomography (SPECT)/CT, improves diagnostic accuracy and patient management. The ongoing advancement of SPECT hardware and software has resulted in the clinical application of novel approaches. For example, whole-body SPECT/CT (WB-SPECT/CT) studies cover multiple consecutive bed positions, similar to positron emission tomography-computed tomography (PET/CT). WB-SPECT/CT proves to be a helpful tool for evaluating bone metastases (BM), reducing equivocal findings, and enhancing user confidence, displaying effective performance in contrast to planar bone scintigraphy (PBS). Consequently, it is increasingly utilized and might substitute PBS, which leads to new questions and issues concerning the acquisition protocol, patient imaging time, and workflow process. Therefore, this review highlights various aspects of WB-SPECT/CT acquisition protocols that need to be considered to help understand WB-SPECT/CT workflow processes and optimize imaging protocols.
Severe Liver Damage in an Obese Patient: Onset of Celiac Disease or Overlap Syndrome?
Authors: Ghiga Gabriela , Boca Laura Otilia , Cojocaru Elena , Stârcea Iuliana Magdalena , Țarcă Elena , Scurtu Ana Maria , Mocanu Maria Adriana , Ioniuc Ileana , Tîrnovanu Mihaela Camelia , Trandafir Laura Mihaela
Published: August 2024

Celiac disease (CeD) is an enteropathy caused by the complex interaction between genetic, environmental, and individual immunological factors. Besides the hallmark of intestinal mucosal damage, CeD is a systemic disorder extending beyond the gastrointestinal tract and impacting various other organs, causing extraintestinal and atypical symptoms. The association between CeD and liver damage has been classified into three main categories: mild and asymptomatic liver injury, autoimmune liver injury, and liver failure. We present a case of severe liver damage with cirrhotic evolution in an obese 12-year-old boy who had been admitted due to generalized jaundice and localized abdominal pain in the right hypochondrium. In the course of investigating the etiology of severe liver disease, toxic, infectious, metabolic, obstructive, and genetic causes were excluded. Despite the patient’s obesity, a diagnosis of CeD was established, and in accordance with autoimmune hepatitis (AIH) criteria, the patient was diagnosed with autoantibody-negative AIH associated to CeD.
Lipidomic Signature of Plasma and Synovial Fluid in Patients with Osteoarthritis: Putative Biomarkers Determined by UHPLC-QTOF-ESI+MS
Authors: Stanciugelu Stefan Iulian , Patrascu Jenel Marian , Patrascu Jenel Marian , Socaciu Carmen , Socaciu Andreea Iulia , Nitusca Diana , Marian Catalin
Published: August 2024

Background: Osteoarthritis (OA) is a prevalent joint condition causing pain and disability, especially in the elderly. Currently, OA diagnosis relies on clinical data and imaging, but recent interest in metabolomics suggests that early biochemical changes in biofluids, particularly synovial fluid (SF), could enable an earlier diagnosis and understanding of the disease. Methods: In this regard, we conducted a lipidomics study in 33 plasma and SF samples from OA patients and 20 OA-free controls to assess the diagnostic value of various lipid metabolites, using UHPLC-QTOF-ESI+MS. Results: In plasma samples, 25 metabolites had area-under-the-curve (AUC) values higher than 0.9, suggesting a very good diagnostic potential for phosphatidic acid PA (16:0/16:0), PA (34:0), phosphatidylethanolamine PE (34:2), glucosylceramide, phosphatidylcholine PC (32:1), and other metabolites while in SF 20, metabolites had AUC values higher than 0.8, the vast majority belonging to lipid metabolism as well. Conclusions: Although the results align with the previous literature, larger cohort studies are necessary to confirm the diagnostic value of the lipid metabolites.
Randomized Clinical Trial of Electrostimulation Therapies as an Adjuvant for the Treatment of Temporomandibular Disorders
Authors: Rodríguez Claudia I. , Angeles Fernando , Borges Socorro A. , Llamosas Eduardo , Morales Julio
Published: August 2024

We carried out a comparison of the neuromuscular and clinical effects produced by electrostimulation therapies, as an adjuvant to the use of occlusal splints (removable muscle relaxation apparatus) in patients with temporomandibular disorders In this simple randomized clinical trial, 91 patients were randomly divided into three groups. Group A (GA) received transcutaneous electrostimulation therapy and an occlusal splint, Group B (GB) received percutaneous electrostimulation therapy and an occlusal splint, and Group C (GC) received an occlusal splint. The neuromuscular activity, as well as the signs and symptoms of each patient, were evaluated every week throughout the treatment (T0 = baseline; T1 = 7 days; T2 = 14 days; T3 = 21 days; T4 = 28 days; and T5 = 35 days). Pain was measured with a visual analog scale, and neuromuscular electrical activity was determined by the root mean square of the masseter muscles through the use of a UNAM-CINVESTAV 1.2 electromyograph. Comparisons were made using ANOVA for repeated measures (p-value = 0.05). The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent, and in the short term for the group treated with transcutaneous electrostimulation therapy as an adjuvant to the use of the occlusal splint. The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent and in a shorter term in the GA (calculation therapy, transcutaneous electrostimulation) and GB (occlusal splint). Transcutaneous electrostimulation is a feasible and faster alternative that was accepted by most of the patients for treating temporomandibular disorders.
Design and Implementation of a Printed Circuit Model for a Wideband Circularly Polarized Bow-Tie Antenna
Authors: Dodd Matthew J. , Elsherbeni Atef Z.
Published: August 2024

A crossed bow-tie antenna design for S- and C-Band (2.44–7.62 GHz) with a peak gain of 7.29 dBi is presented to achieve wideband radiation efficiency greater than 90% and circular polarization with a single feed point. The polarization of the antenna is modeled by the input admittance of crossed bow-ties, and the model predictions are validated by experiments. A wideband matching network is designed to be tightly integrated with the antenna and produce a 103% impedance bandwidth. The matching network is decomposed into an equivalent circuit model, and an analysis is presented to demonstrate the principles of the matching network design. A prototype of the optimized antenna design is fabricated and measured to validate the analysis.
Reducing Noise and Impact of High-Frequency Torque Ripple Caused by Injection Voltages by Using Self-Regulating Random Model Algorithm for SynRMs Sensorless Speed Control
Authors: Guo Yibo , Pan Lingyun , Yang Yang , Gong Yimin , Che Xiaolei
Published: August 2024

For the sensorless control in a low-speed range of synchronous reluctance motors (SynRMs), injecting random high-frequency (HF) square-wave-type voltages has become a widely used and technologically mature method. It can solve the noise problem of traditional injection signal methods. However, all injection signal methods will cause problems such as torque ripple, which causes speed fluctuations. This article proposes a self-regulating random model algorithm for the random injection signal method, which includes a quantity adaptive module for adding additional random processes, an evaluation module for evaluating torque deviation degree, and an updated model module that is used to receive signals from the other two modules and complete model changes and output random model elements. The main function of this algorithm is to create a model that updates to suppress the evaluation value deviation based on the evaluation situation and outputs an optimal sequence of random numbers, thereby limiting speed bias always in a small range; this can reduce unnecessary changes in the output value of the speed regulator. The feasibility and effectiveness of the proposed algorithm and control method have been demonstrated in experiments based on a 5-kW synchronous reluctance motor.