bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Foot Ulcers and Chronic Wounds with Amniotic Membrane in Comorbid Patients: A Successful Experience
Authors: Rodríguez-Valiente Mónica , García-Hernández Ana M. , Fuente-Mora Cristina , Sánchez-Gálvez Javier , García-Vizcaino Eva María , Tristante Barrenechea Elena , Castellanos Escrig Gregorio , Liarte Lastra Sergio David , Nicolás Francisco Jose
Published: October 2024

Chronic wounds are defined as those with disturbances in normal healing. They involve symptoms like exudate, odor, pain or impaired mobility, severely impacting life quality. In the case of patients with additional comorbidities, these are known to aggravate the healing impairment. Amniotic membrane (AM) is gaining attention for its regenerative potential, as it has shown promise in treating hard-to-heal wounds, such as diabetic foot ulcers. This work examines a series of five patients who, while suffering an array of other chronic conditions, were treated with AM for the management of non-healing chronic ulcers. Inclusion criteria involved patients with lesions that have been active at least for six weeks and resistant to multiple treatments, accompanied by complex underlying pathologies affecting cardiovascular, immune or renal functions. Exclusion criteria included untreated active infections and patients undergoing other experimental treatments. The mean age of the patients was 68.4 ± 5.2 years. Wounds were treated once a week with AM, following standardized procedures. The variables measured included pain levels, microorganism presence, wound reduction and the number of AM applications to recovery. The median pain VAS score decreased significantly from seven at the start to two at the end of procedures. Four out of five patients achieved complete epithelialization, while the remaining patient showed significant reductions of 40% in wound size after 14 months. Our results confirm how the application of AM is a safe and effective resource for the management of chronic wounds in patients with serious comorbidities, enhancing patients’ quality of life, firstly by reducing pain, later by allowing recovery. Future research, including molecular analyses of wound exudates before and after AM treatment, can contribute to better understanding and fine tuning of this therapeutic resource.
Insights into CSF-1R Expression in the Tumor Microenvironment
Authors: Tomassetti Caterina , Insinga Gaia , Gimigliano Francesca , Morrione Andrea , Giordano Antonio , Giurisato Emanuele
Published: October 2024

The colony-stimulating factor 1 receptor (CSF-1R) plays a pivotal role in orchestrating cellular interactions within the tumor microenvironment (TME). Although the CSF-1R has been extensively studied in myeloid cells, the expression of this receptor and its emerging role in other cell types in the TME need to be further analyzed. This review explores the multifaceted functions of the CSF-1R across various TME cellular populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), cancer-associated fibroblasts (CAFs), endothelial cells (ECs), and cancer stem cells (CSCs). The activation of the CSF-1R by its ligands, colony-stimulating factor 1 (CSF-1) and Interleukin-34 (IL-34), regulates TAM polarization towards an immunosuppressive M2 phenotype, promoting tumor progression and immune evasion. Similarly, CSF-1R signaling influences MDSCs to exert immunosuppressive functions, hindering anti-tumor immunity. In DCs, the CSF-1R alters antigen-presenting capabilities, compromising immune surveillance against cancer cells. CSF-1R expression in CAFs and ECs regulates immune modulation, angiogenesis, and immune cell trafficking within the TME, fostering a pro-tumorigenic milieu. Notably, the CSF-1R in CSCs contributes to tumor aggressiveness and therapeutic resistance through interactions with TAMs and the modulation of stemness features. Understanding the diverse roles of the CSF-1R in the TME underscores its potential as a therapeutic target for cancer treatment, aiming at disrupting pro-tumorigenic cellular crosstalk and enhancing anti-tumor immune responses.
The Relationship Between MOTS-c K14Q Polymorphism and Sarcopenia, Blood Lipids, and Mental Health in Older Korean Adults
Authors: Kim Shinuk
Published: October 2024

Background/objectives: An East Asian-specific 1382A>C polymorphism in the mitochondrial open reading frame of the 12S rRNA type-c results in an amino acid substitution from Lys (K) to Gln (Q) at the 14th amino acid residue. This study investigated the association between m.1382A>C polymorphism and sarcopenia, blood lipids, and mental health in older Korean adults. Methods: The study included 683 community-dwelling Korean adults (345 men and 338 women) aged 65 years and older. The m.1382A>C polymorphism was genotyped with a 7500 real-time PCR system. Handgrip strength (HGS) was measured, and appendicular skeletal muscle (ASM) mass was calculated. Demographics, blood lipids, falling risk, nutritional intake, cognition function, and depression were additionally measured. Results: Men carrying the C allele had significantly higher ASM (21.6 ± 3.0 vs. 19.5 ± 2.2 kg, p = 0.018), ASM/height2 (7.76 ± 0.76 vs. 7.14 ± 0.62 kg/m2, p = 0.012), lean mass (53.3 ± 6.2 vs. 46.5 ± 4.0 kg, p < 0.001), left HGS (33.3 ± 5.0 vs. 28.9 ± 4.0 kg, p = 0.010), and right HGS (35.6 ± 5.3 vs. 30.9 ± 4.3 kg, p = 0.009) than men carrying the A allele. The genotype differences in ASM (p = 0.017), ASM/height2 (p = 0.011), lean mass (p < 0.001), left HGS (p = 0.010), and right HGS (p = 0.009) remained significant even after adjusting for all measured covariates. By contrast, no significant differences in other measured parameters were found between women carrying the A and C alleles. Conclusions: Our study findings indicate that the m.1382A>C polymorphism may be used as a genetic biomarker of age-related sarcopenia in older Korean men.
Biomimetic Tissue Engineering Strategies for Craniofacial Applications
Authors: Fatima Balderrama Isis , Schafer Sogand , El Shatanofy Muhammad , Bergamo Edmara T. P. , Mirsky Nicholas A. , Nayak Vasudev Vivekanand , Marcantonio Junior Elcio , Alifarag Adham M. , Coelho Paulo G. , Witek Lukasz
Published: October 2024

Biomimetics is the science of imitating nature’s designs and processes to create innovative solutions for various fields, including dentistry and craniofacial reconstruction. In these areas, biomimetics involves drawing inspiration from living organisms/systems to develop new materials, techniques, and devices that closely resemble natural tissue structures and enhance functionality. This field has successfully demonstrated its potential to revolutionize craniofacial procedures, significantly improving patient outcomes. In dentistry, biomimetics offers exciting possibilities for the advancement of new dental materials, restorative techniques, and regenerative potential. By analyzing the structure/composition of natural teeth and the surrounding tissues, researchers have developed restorative materials that mimic the properties of teeth, as well as regenerative techniques that might assist in repairing enamel, dentin, pulp, cementum, periodontal ligament, and bone. In craniofacial reconstruction, biomimetics plays a vital role in developing innovative solutions for facial trauma, congenital defects, and various conditions affecting the maxillofacial region. By studying the intricate composition and mechanical properties of the skull and facial bones, clinicians and engineers have been able to replicate natural structures leveraging computer-aided design and manufacturing (CAD/CAM) and 3D printing. This has allowed for the creation of patient-specific scaffolds, implants, and prostheses that accurately fit a patient’s anatomy. This review highlights the current evidence on the application of biomimetics in the fields of dentistry and craniofacial reconstruction.
A Machine Learning Assisted Non-Enzymatic Electrochemical Biosensor to Detect Urea Based on Multi-Walled Carbon Nanotube Functionalized with Copper Oxide Micro-Flowers
Authors: Zalke Jitendra B. , Bhaiyya Manish L. , Jain Pooja A. , Sakharkar Devashree N. , Kalambe Jayu , Narkhede Nitin P. , Thakre Mangesh B. , Rotake Dinesh R. , Kulkarni Madhusudan B. , Singh Shiv Govind
Published: October 2024

Detecting urea is crucial for diagnosing related health conditions and ensuring timely medical intervention. The addition of machine learning (ML) technologies has completely changed the field of biochemical sensing, providing enhanced accuracy and reliability. In the present work, an ML-assisted screen-printed, flexible, electrochemical, non-enzymatic biosensor was proposed to quantify urea concentrations. For the detection of urea, the biosensor was modified with a multi-walled carbon nanotube-zinc oxide (MWCNT-ZnO) nanocomposite functionalized with copper oxide (CuO) micro-flowers (MFs). Further, the CuO-MFs were synthesized using a standard sol-gel approach, and the obtained particles were subjected to various characterization techniques, including X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and Fourier transform infrared (FTIR) spectroscopy. The sensor’s performance for urea detection was evaluated by assessing the dependence of peak currents on analyte concentration using cyclic voltammetry (CV) at different scan rates of 50, 75, and 100 mV/s. The designed non-enzymatic biosensor showed an acceptable linear range of operation of 0.5–8 mM, and the limit of detection (LoD) observed was 78.479 nM, which is well aligned with the urea concentration found in human blood and exhibits a good sensitivity of 117.98 mA mM−1 cm−2. Additionally, different regression-based ML models were applied to determine CV parameters to predict urea concentrations experimentally. ML significantly improves the accuracy and reliability of screen-printed biosensors, enabling accurate predictions of urea levels. Finally, the combination of ML and biosensor design emphasizes not only the high sensitivity and accuracy of the sensor but also its potential for complex non-enzymatic urea detection applications. Future advancements in accurate biochemical sensing technologies are made possible by this strong and dependable methodology.
Source Localization and Classification of Pulmonary Valve-Originated Electrocardiograms Using Volume Conductor Modeling with Anatomical Models
Authors: Ogawa Kota , Hirata Akimasa
Published: October 2024

Premature ventricular contractions (PVCs) are a common arrhythmia characterized by ectopic excitations within the ventricles. Accurately estimating the ablation site using an electrocardiogram (ECG) is crucial for the initial classification of PVC origins, typically focusing on the right and left ventricular outflow tracts. However, finer classification, specifically identifying the left cusp (LC), anterior cusp (AC), and right cusp (RC), is essential for detailed preoperative planning. This study aims to improve the accuracy of cardiac waveform source estimation and classification in 27 patients with PVCs originating from the pulmonary valve. We utilized an anatomical human model and electromagnetic simulations to estimate wave source positions from 12-lead ECG data. Time-series source points were identified for each measured ECG waveform, focusing on the moment when the distance between the estimated wave source and the pulmonary valve was minimal. Computational analysis revealed that the distance between the estimated wave source and the pulmonary valve was reduced to less than 1 cm, with LC localization achieving errors under 5 mm. Additionally, 74.1% of the subjects were accurately classified into the correct origin (LC, AC, or RC), with each origin demonstrating the highest percentage of subjects corresponding to the targeted excitation origin. Our findings underscore the novel potential of this source localization method as a valuable complement to traditional waveform classification, offering enhanced diagnostic precision and improved preoperative planning for PVC ablation procedures.
Heterogeneous Nuclear Ribonucleoprotein A1 Knockdown Alters Constituents of Nucleocytoplasmic Transport
Authors: Stang Todd E. , Salapa Hannah E. , Clarke Joseph-Patrick W. E. , Popescu Bogdan F. , Levin Michael C.
Published: October 2024

Background/Objectives: Changes in nuclear morphology, alterations to the nuclear pore complex (NPC), including loss, aggregation, and dysfunction of nucleoporins (Nups), and nucleocytoplasmic transport (NCT) abnormalities have become hallmarks of neurodegenerative diseases. Previous RNA sequencing data utilizing knockdown of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) identified enrichment for pathways and changes in RNAs related to nuclear morphology and showed differential expression of key nuclear targets. This suggests that dysfunction of hnRNP A1, which is observed in neurodegenerative diseases, may contribute to abnormalities in nuclear morphology, NPC, and NCT. Methods: We performed knockdown of hnRNP A1 in Neuro-2A cells, a neuronal cell line, to examine nuclear morphology, NPC, and NCT. Results: First, we examined nuclear morphology using Lamin B, wherein we observed increased nuclear envelope abnormalities in cells with hnRNP A1 knockdown as compared to control. To quantify changes in Lamin B, we designed and validated an automated computer-based model, which quantitatively confirmed our observations. Next, we investigated the impact of hnRNP A1 knockdown on components of the NPC and NCT. In line with the previous literature, we found changes in Nups, including altered distribution and reduced protein expression, as well as disrupted NCT. Finally, we validated our findings in multiple sclerosis (MS) brains, a disease with a significant neurodegenerative component caused by hnRNP A1 dysfunction, where neuronal nuclear envelope alterations were significantly increased as compared to controls. Conclusions: Together, these data implicate hnRNP A1 as an important contributor to nuclear morphology, Nup expression and distribution, and NCT and suggest that hnRNP A1 dysfunction may lead to defects in these processes in neurodegenerative diseases.
Temporal Variability in the Incidence and Risk Factors for Pharyngocutaneous Fistula Development after Total Laryngectomy
Authors: Šifrer Robert , Dolenc Maja , Zore Sara Bitenc , Fugina Simon , Jesenko Luka , Strojan Primož
Published: October 2024

Background: This study aimed to analyse the variability in the incidence of the pharyngocutaneous fistula (PCF), the most common complication following a total laryngectomy (TLE), and to identify the underlying causes for fluctuations in incidence rates. Methods: In the retrospective study, the annual PCF incidence data and comprehensive clinicopathologic data from 540 patients who underwent TLE between January 2004 and December 2022 were reviewed. Distinct peri ods of both high and low PCF incidence were identified. Within these periods, patients were categorized into groups with PCF (study groups) and without it (control groups). These groups were statistically compared based on potential risk factors for PCF development. The high-incidence periods were specially analysed for recurring risk factors and the corresponding corrective measures were reviewed. Results: The analysis revealed four high-incidence periods with an overall PCF incidence of 37.61%, along with three low-incidence periods in between with an overall incidence of 19.38%. Surgical wound infection (SWI) and a history of head and neck cancer alongside their related treatments were repeatedly identified as independent risk factors during high-incidence periods, with SWI being the most consistent predictor of PCF development. Conclusions: Continuous monitoring of PCF incidence is crucial, as it allows for the identification of emerging risk factors and the immediate implementation of corrective measures to mitigate these newly identified risk factors.
Review of Current and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma
Authors: Lee Aaron M. , Weaver Alice N. , Acosta Phillip , Harris Lauren , Bowles Daniel W.
Published: October 2024

Head and neck squamous cell carcinoma (HNSCC) is a complex cancer requiring a multidisciplinary approach. For patients with locally or regionally advanced disease, surgery and/or radiation are the cornerstones of definitive treatment. Medical therapy plays an important adjunct role in this setting, typically consisting of a platinum-based regimen given as induction, concurrent, or adjuvant treatment. While relapsed/metastatic HNSCC has historically been a difficult-to-treat disease with poor outcomes, options have considerably improved with the incorporation of biologics and immune checkpoint inhibitors. Clinical trials are ongoing to investigate novel approaches, including new and combination immunotherapies, targeted therapies, therapeutic vaccines, antibody–drug conjugates, and cellular therapies. The results thus far have been mixed, highlighting the knowledge gaps that continue to challenge the medical oncologist treating HNSCC. Here, we present the most updated and broad review of the current treatment landscape in both locoregional and metastatic HNSCC and discuss the expansive future medical therapies under investigation.
Antibody-Based Therapies for Peripheral T-Cell Lymphoma
Authors: Shafagati Nazila , Paul Suman , Rozati Sima , Sterling Cole H.
Published: October 2024

While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody–drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions.
Advanced Imaging for Localized Prostate Cancer
Authors: Albers Patrick , Kinnaird Adam
Published: October 2024

Background/Objectives: Prostate cancer is a prevalent malignancy often presenting without early symptoms. Advanced imaging technologies have revolutionized its diagnosis and management. This review discusses the principles, benefits, and clinical applications of multiparametric magnetic resonance imaging (mpMRI), micro-ultrasound (microUS), and prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET/CT) in localized prostate cancer. Methods: We conducted a comprehensive literature review of recent studies and guidelines on mpMRI, microUS, and PSMA PET/CT in prostate cancer diagnosis, focusing on their applications in biopsy-naïve patients, those with previous negative biopsies, and patients under active surveillance. Results: MpMRI has demonstrated high sensitivity and negative predictive value in detecting clinically significant prostate cancer (csPCa). MicroUS, a newer technology, has shown promising results in early studies, with sensitivity and specificity comparable to mpMRI. PSMA PET/CT has emerged as a highly sensitive and specific imaging modality, particularly valuable for staging and detecting metastatic disease. All three technologies have been incorporated into urologic practice for prostate cancer diagnosis and management, with each offering unique advantages in different clinical scenarios. Conclusions: Advanced imaging techniques, including mpMRI, microUS, and PSMA PET/CT, have significantly improved the accuracy of prostate cancer diagnosis, staging, and management. These technologies enable more precise targeting of suspicious lesions during biopsy and therapy planning. However, further research, especially randomized controlled trials, is needed to fully establish the optimal use and inclusion of these imaging modalities in various stages of prostate cancer care.
Effect of Fluorescence Lymph Node Mapping on Improving Diagnostic Values of CT D3 Lymph Node Staging for Right-Sided Colon Cancer
Authors: Son Gyung Mo , Kim Tae Un , Yun Mi Sook , Kim ChangYeop , Lee In Young , Park Su Bum , Shin Dong-Hoon , Ha Gi Won
Published: October 2024

Background/Objectives: This study evaluated the impact of fluorescence lymph node mapping (FLNM) using indocyanine green (ICG) on the diagnostic accuracy of preoperative computed tomography (CT) in right-sided colon cancer. Methods: A total of 218 patients who underwent laparoscopic right hemicolectomy with D3 lymph node dissection (LND) were analyzed: 86 patients in the FLNM group and 132 in the conventional surgery group. The FLNM technique allowed for enhanced intraoperative visualization of lymph node (LN) and more precise dissection, improving the identification of metastatic LNs. The diagnostic value of preoperative CT staging was assessed in both the FLNM and control groups by calculating the apparent prevalence, true prevalence, sensitivity, specificity, positive predictive value (PPV), negative predictive value, positive likelihood ratio (PLR), negative likelihood ratio, false positive and false negative proportions, and accuracy. Results: FLNM increased the accuracy of CT staging for detecting D3 LN metastasis in advanced cancer cases, with a higher PPV, PLR, and accuracy. In the FLNM group, the false-positive rate was significantly reduced, and the specificity was higher compared to the control group. Multivariate analysis identified FLNM as an independent factor associated with improved D3 LN metastasis detection. These findings suggest that incorporating FLNM into surgical procedures enhances the diagnostic value of preoperative CT by improving the precision of LND, particularly in patients with advanced colon cancer. Conclusions: The use of FLNM for D3 LND enhances the diagnostic accuracy of cN staging in right-sided colon cancer by improving surgical precision.
Relationship of Immune-Related Adverse Events with Tumor Response and Prognosis in Esophageal Squamous Cell Carcinoma Following Nivolumab Monotherapy
Authors: Hamai Yoichi , Ibuki Yuta , Kurokawa Tomoaki , Hirohata Ryosuke , Ohsawa Manato , Kitasaki Nao , Emi Manabu , Okada Morihito
Published: October 2024

Background: Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are limited. Methods: We assessed the relationship of irAEs with tumor response and survival in 82 consecutive patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy. Results: We observed irAEs in 24 (29.3%) patients, with the overall response and disease control rates in the irAE-positive group being significantly better than those in the irAE-negative group (both p < 0.0001). During the entire period and within 8 weeks of nivolumab initiation, progression-free and overall survivals (PFS and OS, respectively) were significantly better in patients with grade1/2 irAEs than in those without. Univariate and multivariate analyses indicated grade1/2 irAEs during the entire period and within 8 weeks as independent covariates for PFS (entire period: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.16–0.49, p < 0.001; within 8 weeks: HR 0.46, 95% CI 0.23–0.93, p = 0.03) and OS (entire period: HR 0.24, 95% CI 0.13–0.44, p < 0.001; within 8 weeks: HR 0.41, 95% CI 0.18–0.92, p = 0.03). Conclusions: Grade1/2 irAEs during the entire treatment period and within 8 weeks of nivolumab initiation were significantly associated with improved tumor response and survival in patients with advanced ESCC treated with nivolumab monotherapy. Therefore, mild irAEs may be predictive markers for the response and prognosis of ESCC following ICI treatment.
Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology
Authors: Wiggins Russell , Woo Jihoo , Mito Shizue
Published: October 2024

Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical structure and utilization of novel nanotechnologies, like electrospraying and supercritical fluids, to improve drug delivery. For example, niclosamide derivatives, such as o-alkylamino-tethered niclosamide derivates, niclosamide ethanolamine salt, and niclosamide piperazine salt, have demonstrated increased water solubility without compromising anticancer activity in vitro. Additionally, this review briefly discusses recent findings on the first pass metabolism of niclosamide in vivo, the role of cytochrome P450-mediated hydroxylation, UDP-glucuronosyltransferase mediated glucuronidation, and how enzymatic inhibition could enhance niclosamide bioavailability. Ultimately, there is a need for researchers to synthesize, evaluate, and improve upon niclosamide derivatives while experimenting with the employment of nanotechnologies, such as targeted delivery and nanoparticle modification, as a way to improve drug administration. Researchers should strive to improve drug-target accuracy, its therapeutic index, and increase the drug’s efficacy as an anti-neoplastic agent.
Impact of the Immune Landscape in Follicular Lymphoma: Insights into Histological Transformation in the Rituximab Era
Authors: Enemark Marie Hairing , Jensen Maja Lund , Andersen Maja Dam , Plesner Trine Lindhardt , Hamilton-Dutoit Stephen , Ludvigsen Maja
Published: October 2024

Background: Follicular lymphoma (FL) presents significant clinical heterogeneity, with some patients experiencing transformation into an aggressive disease, a key contributor to FL-related mortality. Based on gene expression profiles, this study aimed to provide insights into immunological differences associated with transformation. Methods: Gene expression analysis using the NanoString nCounter Tumor Signaling 360 Panel was performed on diagnostic lymphoma samples from 70 FL patients diagnosed in the rituximab era, either non-transforming FL (nt-FL, n = 34) or subsequently transforming FL (st-FL, n = 36), with paired high-grade transformed FL (tFL, n = 36) samples available. In silico immunophenotyping was performed to infer immune cell infiltration using the CIBERSORTx algorithm. Results: The gene expression analysis revealed 164 significantly differentially expressed genes, distinguishing st-FL from nt-FL and generally presenting an upregulation of B cell-related genes (CD40, IRF4, RELB), immunosuppressive molecules (IL10, SOCS3), and immune checkpoint molecules (CD276, TIM3). Analysis of immune cell proportions indicated significant differences in infiltrates of M1-like macrophages (p = 0.007) and neutrophils (p = 0.012) in nt-FL versus st-FL samples. Transformation-free survival (TFS) was associated with high numbers of both these cellular subsets (p = 0.006 and 0 = 0.002, respectively). This was even more evident when combined with inferior TFS in lymphomas with high infiltrates of both cell types (p < 0.001). After transformation, tFL samples showed a reduction in T follicular helper cells (p = 0.008) and an increase in immunosuppressive M2-like macrophages and neutrophils (p < 0.001 and p = 0.028, respectively). Conclusion: By elucidating the distinct molecular and immune landscapes of FL at the time of diagnosis and transformation, this study underscores the importance of immune microenvironment in FL transformation and patient outcome.
Correction: Becker et al. Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response. Cancers 2023, 15, 5597
Authors: Becker Anne-Sophie , Kluge Cornelius , Schofeld Carsten , Zimpfer Annette Helene , Schneider Björn , Strüder Daniel , Redwanz Caterina , Ribbat-Idel Julika , Idel Christian , Maletzki Claudia
Published: October 2024

In the original publication [...]
Decreased Circulating Gonadotropin-Releasing Hormone Associated with Keratoconus
Authors: Escandon Paulina , Choi Alexander J. , Mabry Steve , Nicholas Sarah E. , Cunningham Rebecca L. , Redden Liam , Murphy David A. , Riaz Kamran M. , McKay Tina B. , Karamichos Dimitrios
Published: October 2024

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic–pituitary–gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.
Early-Life Respiratory Syncytial Virus (RSV) Infection Triggers Immunological Changes in Gut-Associated Lymphoid Tissues in a Sex-Dependent Manner in Adulthood
Authors: Liong Stella , Liong Felicia , Mohsenipour Mitra , Hill-Yardin Elisa L. , Miles Mark A. , Selemidis Stavros
Published: October 2024

Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer’s patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases.
Pleiotropic Effects of Resveratrol on Aging-Related Cardiovascular Diseases—What Can We Learn from Research in Dogs?
Authors: Grzeczka Arkadiusz , Graczyk Szymon , Kordowitzki Pawel
Published: October 2024

Resveratrol (RES) is a polyphenol with natural anti-inflammatory and antioxidant properties. It is found in abundance in plants, i.e., grapes and mulberry fruit. In addition, synthetic forms of RES exist. Since the discovery of its specific biological properties, RES has emerged as a candidate substance not only with modeling effects on the immune response but also as an important factor in preventing the onset and progression of cardiovascular disease (CVD). Previous research provided strong evidence of the effects of RES on platelets, mitochondria, cardiomyocytes, and vascular endothelial function. In addition, RES positively affects the coagulation system and vasodilatory function and improves blood flow. Not only in humans but also in veterinary medicine, cardiovascular diseases have one of the highest incidence rates. Canine and human species co-evolved and share recent evolutionary selection processes, and interestingly, numerous pathologies of companion dogs have a human counterpart. Knowledge of the impact of RES on the cardiovascular system of dogs is becoming clearer in the literature. Dogs have long been recognized as valuable animal models for the study of various human diseases as they share many physiological and genetic similarities with humans. In this review, we aim to shed light on the pleiotropic effects of resveratrol on cardiovascular health in dogs as a translational model for human cardiovascular diseases.
AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling
Authors: Nakanishi Takashi , Koma Yu-ichiro , Miyako Shoji , Torigoe Rikuya , Yokoo Hiroki , Omori Masaki , Yamanaka Keitaro , Ishihara Nobuaki , Tsukamoto Shuichi , Kodama Takayuki , Nishio Mari , Shigeoka Manabu , Yokozaki Hiroshi , Kakeji Yoshihiro
Published: October 2024

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.
Chicken Embryo Fibroblast Viability and Trans-Differentiation Potential for Cultured Meat Production Across Passages
Authors: Kim So-Hee , Kim Chan-Jin , Lee Eun-Yeong , Hwang Young-Hwa , Joo Seon-Tea
Published: October 2024

This study was conducted to analyze the viability of primary chicken embryo fibroblasts and the efficiency of adipogenic trans-differentiation for cultured meat production. In isolating chicken embryo fibroblasts (CEFs) from a heterogeneous cell pool containing chicken satellite cells (CSCs), over 90% of CEFs expressed CD29 and vimentin. The analysis of the proliferative capabilities of CEFs revealed no significant differences in EdU-positive cells (%), cumulative cell number, doubling time, and growth rate from passage 1 to passage 9 (p > 0.05). This indicates that CEFs can be isolated by 2 h of pre-plating and survive stably up to passage 9, and that primary fibroblasts can serve as a valuable cell source for the cultured meat industry. Adipogenic trans-differentiation was induced up to passage 9 of CEFs. As passages increased, lipid accumulation and adipocyte size significantly decreased (p < 0.05). The reduced differentiation rate of primary CEFs with increasing passages poses a major challenge to the cost and efficiency of cultured meat production. Thus, effective cell management and the maintenance of cellular characteristics for a long time are crucial for ensuring stable and efficient cultured fat production in the cultured meat industry.
Asparagine614 Determines the Transport and Function of the Murine Anti-Aging Protein Klotho
Authors: Fanaei-Kahrani Zahra , Kaether Christoph
Published: October 2024

Klotho is an anti-aging protein whose deletion significantly reduces lifespan in mice, while its over-expression increases lifespan. Klotho is a type-I transmembrane protein that is N-glycosylated at eight positions within its ectodomain. Our study demonstrates that N-glycosylation or mutation at position N614, but not at N161, N285, or N346 in mouse Klotho, is critically involved in the transport of Klotho out of the endoplasmic reticulum (ER). Consequently, while wild-type Klotho-EGFP as well as the N-glycosylation mutants N161Q, N285Q, and N346Q were present at the plasma membrane (PM), only small amounts of the N614Q Klotho-EGFP were present at the PM, with most of the protein accumulating in the ER. Protein interactome analysis of Klotho-EGFP N614Q revealed increased interactions with proteasome-related proteins and proteins involved in ER protein processing, like heat shock proteins and protein disulfide isomerases, indicative of impaired protein folding. Co-immunoprecipitation experiments confirmed the interaction of Klotho-EGFP N614Q with ER chaperons. Interestingly, despite the low amounts of Klotho-EGFP N614Q at the PM, it efficiently induced FGF receptor-mediated ERK activation in the presence of FGF23, highlighting its efficacy in triggering downstream signaling, even in limited quantities at the PM.
Perceived Experiences of Families of Children with Unilateral Cerebral Palsy in the Implementation of a Task-Specific Intervention in the Home Environment with an Upper Limb Splint: A Qualitative Study
Authors: Roldán-Pérez Patricia , Abuín-Porras Vanesa , Rodríguez-Costa Isabel , Ortiz-Lucas María , Bellosta-López Pablo , Buesa-Estéllez Almudena
Published: October 2024

Introduction: Specific home tasks and the use of splints seem to positively affect altered structures and functions, as well as the activities and participation, of children with unilateral cerebral palsy (UCP). However, how did families experience the implementation of these therapies? Objective: To describe the experiences as they were perceived by the families of children with UCP before, during, and after a specific task intervention in the home environment, either with or without upper limb splinting. Methods: A qualitative, descriptive, phenomenological study was conducted in a natural environment. Fourteen families caring for children with UCP who participated in a previous randomized controlled trial were included. Data from unstructured and semi-structured interviews were analyzed through a thematic analysis. Results: Fourteen families (17 parents, age 37–47 years) caring for children with UCP (14 children, ages 6–10 years, 64% female) were interviewed. The following three themes emerged: “The project itself”, in which families explained that they enrolled because of their trust in therapists; “Results obtained”, where the main improvement was the integration of the assisting hand in the body schema; and “Lights and shadows”, where families showed what they learned as positive points and some negative aspects related to the assessments and splints. Conclusions: The perceptions of the parents after the specific task intervention in the home environment showed a greater integration of the most affected side. Nevertheless, although the support of a splint on the hand can have beneficial results in terms of performance, other drawbacks leading to the disuse of the splint were highlighted.
Research Progress on Polysaccharide Composite Films and Coatings with Antioxidant and Antibacterial Ingredients to Extend the Shelf Life of Animal-Derived Meat
Authors: Yuan Ming , Mei Jun , Xie Jing
Published: October 2024

Animal-derived meat is rich in proteins and other nutrients, but is prone to spoilage during storage, including microbial contamination and fat oxidation. Therefore, there is an urgent need to find effective solutions to extend the shelf life of animal-derived meat. Polysaccharides are natural macromolecules containing multi-hydroxyl structures and functional groups, which have good solubility, film-forming properties, etc., and can form edible films. Polysaccharide films can be combined with biopolymers, nanoparticles, and natural active agents to improve their properties and enhance the antioxidant and antimicrobial activities of the films. This review summarizes the various sources of polysaccharides, such as chitosan, hyaluronic acid, sodium alginate, carrageenan, starch, and pullulan polysaccharides and their combination with different substances to extend the shelf life of animal-derived meat. This review may serve as a reference for further development of polysaccharides in animal-derived meat preservation.
High-Speed Removal Process for Organic Polymers by Non-Thermal Atmospheric-Pressure Spark Discharge at Room Temperature and Its Mechanism
Authors: Sakamoto Yoshihiro , Tsutsumi Takayoshi , Tanaka Hiromasa , Ishikawa Kenji , Hashizume Hiroshi , Hori Masaru
Published: October 2024

Heel marks (HMs) are a type of dirt stain consisting of polyester-based urethane rubber on polyvinyl chloride (PVC) floor surfaces. The rapid removal of HMs was achieved by using non-thermal atmospheric-pressure plasma technology. Mimetic HMs were prepared by coating PVC floor samples with HMs to a thickness of 13.9 μm. The removal area, thickness, and volume were measured after applying spark discharges at high voltage and a repetition rate of 50 kHz. The treated surfaces were analyzed by using X-ray photoelectron spectroscopy (XPS) and pyrolysis–gas chromatography with time-of-flight mass spectrometry (Py-GC/TOFMS). Removal rates of 20 mm2/min in area, 52 mm3/min in volume, and 7 μm/min in depth were achieved with an inter-electrode distance of 10.0 mm and an air flow rate of 20 standard liters per minute. A removal depth of 10 μm/min was achieved without air supply. The mechanism of stain removal by spark discharge was modeled by decomposing the original high-molecular-weight molecules in polyester-based urethane rubber into low-molecular-weight molecules, such as methylene diisocyanate (MDI) components. The results of this study may facilitate the development of a novel electric vacuum cleaner capable of removing floor stains.
Periodically Sinusoidal Magnetic Stray Field and Improved Film Quality of CoMnP Micro-Magnet Arrays for Magnetic Encoders by Electrodeposition with the Assistance of Ultrasound
Authors: Xu Geng-Hua , Chang Jung-Yen , Hsueh Hsiang-Chun , Lin Chiao-Chi
Published: October 2024

Magnetic encoders are composed of a magnetic sensor, a hard magnetic recording medium and a signal processing circuit. Electrodeposited micro-magnet arrays produced by micro-fabrication are promising recording media for enhancing encoder performance. However, two major engineering issues have yet to be resolved. One issue is an unknown relationship between the feature sizes of micro-magnet arrays and their stray field shapes, and another issue is the formation of micro-cracks due to the built-up residual stresses of thick films. In this study, we investigated the effect of feature sizes on the emanating stray field shape at various observation heights. Feature sizes include two height (i.e., film thickness) values of 78 μm and 176 μm, and both width and spacing with three values of 360 μm, 520 μm and 680 μm. Ultrasound-assisted agitation was adopted for investigating the effects of electrodepositing current densities on the film crystalline microstructures and magnetic properties. Narrowing the width of micro-magnets helps the stray field to become a sinusoidal profile. Thinner film, i.e., thickness 78 μm in this study, supports the stray field taking on a sinusoidal profile. Moreover, the spacing between the micro-magnets plays a key factor in determining the shape of the stray field. Under 37 kHz/156 W ultrasound agitation, the optimal hard magnetic properties of electrodeposited CoMnP films are residual magnetization 2329 G and coercivity 968 Oe by a current density of 10.0 mA/cm2. Ultrasound-assisted electrodeposition, along with duly designed feature size, facilitates the micro-magnet arrays having a sinusoidal stray field shape using high quality films. Furthermore, for the first time, a systematic understanding of feature-size-dependent stray field evolution and improved polarities quality has been realized for the recording media of sinusoidal magnetic encoders.
Structure and Properties of Thin Films Prepared on Flexible Substrates from SnCl4-Derived Solutions
Authors: Dmitriyeva Elena A. , Nurbaev Bedelbek M. , Bondar Ekaterina A. , Kovalenko Anastasiya S. , Nikolaev Anton M. , Shilova Olga A.
Published: October 2024

Thin transparent films of SnO2 were obtained from aqueous–alcohol solutions of SnCl4 on a flexible polyethylene terephthalate (PET) substrate by spray pyrolysis at 100 °C. The influence of the addition of aqueous ammonia to the film-forming solution on the different properties has been studied. Properties studied include surface morphology, phase composition and transparency of the formed films and the crystallization processes and band gap of the film material. It was found that the addition of aqueous ammonia causes the formation of skeletal crystals (NH4)2[SnCl6] with a perovskite structure in the film structure. The resulting films are promising for use in the technology of manufacturing flexible solar cells.
Molybdenum-Modified Niobium Oxide: A Pathway to Superior Electrochromic Materials for Smart Windows and Displays
Authors: Amate Rutuja U. , Morankar Pritam J. , Teli Aviraj M. , Beknalkar Sonali A. , Jeon Chan-Wook
Published: October 2024

Electrochromic materials enable the precise control of their optical properties, making them essential for energy-saving applications such as smart windows. This study focuses on the synthesis of molybdenum-doped niobium oxide (Mo-Nb2O5) thin films using a one-step hydrothermal method to investigate the effect of Mo doping on the material’s electrochromic performance. Mo incorporation led to distinct morphological changes and a transition from a compact granular structure to an anisotropic rod-like feature. Notably, the MN-3 (0.3% Mo) sample displayed an optimal electrochromic performance, achieving 77% optical modulation at 600 nm, a near-perfect reversibility of 99%, and a high coloration efficiency of 89 cm2/C. Additionally, MN-3 exhibited excellent cycling stability, with only 0.8% degradation over 5000 s. The MN-3 device also displayed impressive control over color switching, underscoring its potential for practical applications. These results highlight the significant impact of Mo doping on improving the structural and electrochromic properties of Nb2O5 thin films, offering improved ion intercalation and charge transport. This study underscores the potential of Mo-Nb2O5 for practical applications in energy-efficient technologies.