bluuebunny/crossref_metadata_2025 huggingface dataset:
Photothermal-Conversion-Enhanced LiMn2O4 Pouch Cell Performance for Low-Temperature Resistance: A Theoretical Study
Authors: Tian Shuo , Liu Zhifeng , Yang Qiang , Xu Na , Li Xiang , Wang Dejun , Liu Runru , Lü Wei
Published: July 2023

Lithium-ion batteries (LIBs) suffer from charging difficulties, capacity decay, and severe ageing in a low-temperature environment. In this work, we suggest a theoretical study and strategy for improving the low-temperature resistance of LiMn2O4(LMO) pouch cells, by introducing a photothermal conversion layer composed of copper and single-walled carbon nanotubes. A three-dimensional electrochemical–thermal coupling model for a lithium manganate battery is established, in which the photothermal conversion layer is attached on the surface of the cathode collector, and the effect of lug design is also discussed. The changes in the battery temperature field, and improvements in electrochemical performance before and after light preheating, are analyzed. The results show that, when the photothermal conversion film is applied, the LMO pouch cell’s temperature rises 2.7 °C/min in a −5 °C environment, and the surface-temperature averaging is improved. The concentration of lithium embedded in the anode is significantly increased, and the charging speed is enhanced by 20%. The batteries with a single-sided lug design exhibit better performance compared with those with a two-sided lug design. Validation of the presented model is performed, by comparing it with the experimental Panasonic UF653445ST commercial battery datasheet. This work provides theoretical guidance on improving the low-temperature performance of pouch cells, based on the photothermal conversion method.
A Next-Generation 3D Tissue-Engineered Model of the Human Brain Microvasculature to Study the Blood-Brain Barrier
Authors: Galpayage Dona Kalpani N. Udeni , Ramirez Servio H. , Andrews Allison M.
Published: July 2023

More than a billion people are affected by neurological disorders, and few have effective therapeutic options. A key challenge that has prevented promising preclinically proven strategies is the translation gap to the clinic. Humanized tissue engineering models that recreate the brain environment may aid in bridging this translational gap. Here, we showcase the methodology that allows for the practical fabrication of a comprehensive microphysicological system (MPS) of the blood-brain barrier (BBB). Compared to other existing 2D and 3D models of the BBB, this model features relevant cytoarchitecture and multicellular arrangement, with branching and network topologies of the vascular bed. This process utilizes 3D bioprinting with digital light processing to generate a vasculature lumen network surrounded by embedded human astrocytes. The lumens are then cellularized with primary human brain microvascular endothelial cells and pericytes. To initiate mechanotransduction pathways and complete maturation, vascular structures are continuously perfused for 7 days. Constructs are validated for complete endothelialization with viability dyes prior to functional assessments that include barrier integrity (permeability) and immune-endothelial interactions. This MPS has applications for the study of novel therapeutics, toxins, and elucidating mechanisms of pathophysiology.
The Contribution of Various In Vitro Methodologies to Comprehending the Filling Ability of Root Canal Pastes in Primary Teeth
Authors: El Hachem Claire , Chedid Jean Claude Abou , Nehme Walid , Kaloustian Marc Krikor , Ghosn Nabil , Rabineau Morgane , Kharouf Naji , Haikel Youssef , Mancino Davide
Published: July 2023

A void-free obturation during root canal treatment on primary teeth is currently very difficult to attain. In this study, the pulpectomy filling abilities of Bio-C Pulpecto (Angelus, Basil, Londrina, Paraná, Brazil) and of zinc oxide eugenol, or “ZOE” (DenPro, Prevest, New York, NY, USA), were compared using several in vitro techniques. Therefore, 30 primary anterior teeth were used in the present in vitro study. Analysis of variance (ANOVA), including a multiple comparison procedure (Holm-Sidak method, Dunn’s Method, or Tukey test), was used. On micro-CT, Bio-C Pulpecto exhibited higher void percentages than did ZOE (10.3 ± 3.8%, and 3.5 ± 1.3%), respectively (p < 0.05). With digital microscopy, higher total void percentages were found in the BC (13.2 ± 26.7%) group compared to the ZOE (2.7 ± 2.8%) group (p < 0.05). With the CLSM, mean tubular penetration depths were higher for Bio-C Pulpecto than for ZOE in all canal thirds (p < 0.05). SEM images demonstrated no tags into dentinal tubules in either group throughout the three thirds. Moreover, higher statistically significant flowability was found for Bio-C (2.657 ± 0.06 mm) compared to ZOE (1.8 ± 0.13 mm) (p < 0.05). The findings of this study indicate that neither ZOE nor Bio-C Pulpecto appears to meet the criteria for an ideal root canal filling paste for primary teeth. This study laid the groundwork for future research by determining how micro-CT, digital microscopy, SEM, and CLSM contribute to our understanding of the filling process of primary teeth. More thorough research on the mechanism of root canal obturation on primary teeth is required to achieve a long-term successful root canal therapy in young children.
A New Medical Analytical Framework for Automated Detection of MRI Brain Tumor Using Evolutionary Quantum Inspired Level Set Technique
Authors: Darwish Saad M. , Abu Shaheen Lina J. , Elzoghabi Adel A.
Published: July 2023

Segmenting brain tumors in 3D magnetic resonance imaging (3D-MRI) accurately is critical for easing the diagnostic and treatment processes. In the field of energy functional theory-based methods for image segmentation and analysis, level set methods have emerged as a potent computational approach that has greatly aided in the advancement of the geometric active contour model. An important factor in reducing segmentation error and the number of required iterations when using the level set technique is the choice of the initial contour points, both of which are important when dealing with the wide range of sizes, shapes, and structures that brain tumors may take. To define the velocity function, conventional methods simply use the image gradient, edge strength, and region intensity. This article suggests a clustering method influenced by the Quantum Inspired Dragonfly Algorithm (QDA), a metaheuristic optimizer inspired by the swarming behaviors of dragonflies, to accurately extract initial contour points. The proposed model employs a quantum-inspired computing paradigm to stabilize the trade-off between exploitation and exploration, thereby compensating for any shortcomings of the conventional DA-based clustering method, such as slow convergence or falling into a local optimum. To begin, the quantum rotation gate concept can be used to relocate a colony of agents to a location where they can better achieve the optimum value. The main technique is then given a robust local search capacity by adopting a mutation procedure to enhance the swarm’s mutation and realize its variety. After a preliminary phase in which the cranium is disembodied from the brain, tumor contours (edges) are determined with the help of QDA. An initial contour for the MRI series will be derived from these extracted edges. The final step is to use a level set segmentation technique to isolate the tumor area across all volume segments. When applied to 3D-MRI images from the BraTS’ 2019 dataset, the proposed technique outperformed state-of-the-art approaches to brain tumor segmentation, as shown by the obtained results.
Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials
Authors: Stalder Stephanie A. , van der Lely Stéphanie , Anderson Collene E. , Birkhäuser Veronika , Curt Armin , Gross Oliver , Leitner Lorenz , Mehnert Ulrich , Schubert Martin , Tornic Jure , Kessler Thomas M. , Liechti Martina D.
Published: July 2023

Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position—lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting.
Diagnostic Accuracy of Adrenal Iodine-131 6-Beta-Iodomethyl-19-Norcholesterol Scintigraphy for the Subtyping of Primary Aldosteronism
Authors: Araujo-Castro Marta , Paja Fano Miguel , González Boillos Marga , Pascual-Corrales Eider , García Cano Ana María , Parra Ramírez Paola , Martín Rojas-Marcos Patricia , Vicente Delgado Almudena , Casteràs Anna , Puig Albert , García Sanz Iñigo , Díaz Guardiola Patricia , Robles Lázaro Cristina , Núñez Miguel Antonio Sampedro , Guerrero-Vázquez Raquel , del Castillo Tous María , Michalopoulou Alevras Theodora , Tenes Rodrigo Susana , Hanzu Felicia A.
Published: July 2023

Purpose: To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. Methods: A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. Results: A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707–0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782–0.957]. Conclusion: The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.
Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged gpr27 Knockout Zebrafish
Authors: Rutkove Seward B. , Chen Zsu-Zsu , Pandeya Sarbesh , Callegari Santiago , Mourey Tyler , Nagy Janice A. , Nath Anjali K.
Published: July 2023

Throughout a vertebrate organism’s lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy (p < 0.000001, q = 0.000002; p = 0.000004, q = 0.000006; p = 0.000867, q = 0.000683, respectively). Moreover, these same measurements exhibited strong correlations with an established morphometric parameter of muscle atrophy (myofiber cross-sectional area), as determined by histological-based morphometric analysis (r = 0.831, p = 2 × 10−12; r = 0.6959, p = 2 × 10−8; and r = 0.7220; p = 4 × 10−9, respectively). Finally, the genetic deletion of gpr27, an orphan G-protein coupled receptor (GPCR), exacerbated the atrophy of skeletal muscle in aged animals, as evidenced by both sEIM and histology. In conclusion, the data here show that surface EIM techniques can effectively discriminate between healthy young and sarcopenic aged muscle as well as the advanced atrophied muscle in the gpr27 KO animals. Moreover, these studies show how EIM values correlate with cell size across the animals, making it potentially possible to utilize sEIM as a “virtual biopsy” in zebrafish to noninvasively assess myofiber atrophy, a valuable measure for muscle and gerontology research.
The Impact of Ethnicity and Age on Distribution of Metastases in Patients with Upper Tract Urothelial Carcinoma: Analysis of SEER Data
Authors: Tufano Antonio , Perdonà Sisto , Viscuso Pietro , Frisenda Marco , Canale Vittorio , Rossi Antonio , Del Prete Paola , Passaro Francesco , Calarco Alessandro
Published: July 2023

Upper tract urothelial carcinoma (UTUC) constitutes a rare and aggressive entity accounting for 5% to 10% of all urothelial tumors. The importance of stratification and disparities according to ethnicity and age has never been tested in a sufficiently large sample of patients with metastatic UTUC (mUTUC). We conducted this study to address this void, and we hypothesized that the distribution of metastases may vary according to age and ethnicity. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016), we identified 1115 patients with mUTUC. The chi-square and t-test tests were used to examine statistical significance in terms of proportions and mean differences. A total of 925 (83.0%) patients were Caucasians, while 190 (17.0%) were African Americans. Among both ethnicities, lungs were the most common metastatic site (39.1% vs. 48.9%). Brain metastases were infrequent among both ethnicities (1.2 vs. 2.6%; p = 0.13). The trends in the lung metastases decreased with age from 42.3% to 36.6% (p = 0.010) among Caucasians, whereas they increased among African Americans from 34.0% to 51.7% (p = 0.04). Overall, 32.8% of Caucasians and 40.5% of African Americans exhibited more than one metastatic site. Among Caucasians, increasing age was associated with lower rates of having multiple metastatic sites (from 34.3% to 30.2%) (p = 0.004). According to our multivariable analyses, younger age was associated with an increased risk of lung (OR: 1.29, 95% CI 1.04–1.71; p = 0.045) and bone metastases (OR: 1.34, 95% CI 1.07–1.79; p = 0.046). Racial differences exist in the distribution of mUTUC metastasis and vary according to age. Our findings may also be considered in the design of randomized trials.
Development of Therapy Based on the Exploration of Biological Events Underlying the Pathogenetic Mechanisms of Chronic Hepatitis B Infection
Authors: Akbar Sheikh Mohammad Fazle , Al Mahtab Mamun , Yoshida Osamu , Aguilar Julio , Gerardo Guillen Nieto , Hiasa Yoichi
Published: July 2023

According to the World Health Organization (WHO), an estimated 296 million people are chronically infected with hepatitis B virus (HBV). Approximately 15–25% of these people develop complications such as advanced chronic liver diseases (ACLDs). Mortality due to HBV-related complications accounted for an estimated 882,000 deaths in 2019. Potent preventive vaccines have already restricted new HBV infections, and several drugs are available to treat chronic HBV infections. However, the positive impacts of these drugs have been recorded in only a few patients with chronic HBV infection. These drugs do not show long-term efficacy and cannot halt the progression to complications. Thus, more effective and evidence-based therapeutic strategies need to be urgently developed for patients with chronic HBV infection. CHB is a pathological entity induced by HBV that progresses due to impaired host immunity. This indicates the inherent limitations of antiviral-drug-based monotherapy for treating patients with chronic HBV infection. Additionally, commercially available antiviral drugs are not available to patients in developing and resource-constrained countries, posing a challenge to achieving the following WHO goal: “Elimination of Hepatitis by 2030”. As such, this review aimed to provide insights regarding evidence-based and effective management strategies for chronic HBV infection.
Combined Band and Plate Fixation as a New Individual Option for Patients at Risk of Sternal Complications after Cardiac Surgery: A Single-Center Experience
Authors: Miazza Jules , Vasiloi Ion , Koechlin Luca , Gahl Brigitta , Reuthebuch Oliver , Eckstein Friedrich S. , Santer David
Published: July 2023

Due to the advent of interventional therapies for low- and intermediate-risk patients, case complexity has increased in cardiac surgery over the last decades. Despite the surgical progress achieved to keep up with the increase in the number of high-risk patients, the prevention of sternal complications remains a challenge requiring new, individualized sternal closure techniques. The aim of this study was to evaluate the safety and feasibility, as well as the in-hospital and long-term outcomes, of enhanced sternal closure with combined band and plate fixation using the new SternaLock® 360 (SL360) system as an alternative to sternal wiring. From 2020 to 2022, 17 patients underwent enhanced sternal closure using the SL360 at our institution. We analyzed perioperative data, as well as clinical and radiologic follow-up data. The results were as follows: In total, 82% of the patients were treated with the SL360 based on perioperative risk factors, while in 18% of cases, the SL360 was used for secondary closure due to sternal instability. No perioperative complications were observed. We obtained the follow-up data of 82% of the patients (median follow-up time: 141 (47.8 to 511.5) days), showing no surgical revision, no sternal instability, no deep wound infections, and no sternal pain at the follow-up. In one case, a superficial wound infection was treated with antibiotics. In conclusion, enhanced sternal closure with the SL360 is easy to perform, effective, and safe. This system might be considered for both primary and secondary sternal closure in patients at risk of sternal complications.
Lack of Influence of Non-Overlapping Mutations in BRAF, NRAS, or NF1 on 12-Month Best Objective Response and Long-Term Survival after Checkpoint Inhibitor-Based Treatment for Metastatic Melanoma
Authors: Panning Alyssa , Samlowski Wolfram , Allred Gabriel
Published: July 2023

Background: Non-overlapping somatic mutations in BRAF, NRAS, or NF1 genes occur in 85% of metastatic melanoma patients. It is not known whether these mutations affect immunotherapy outcome. Materials and methods: Next-Gen sequencing of 324 oncogenes was performed in 73 metastatic melanoma patients. A retrospective review of immunotherapy outcome was performed. Results: BRAF fusions/internal rearrangements, BRAF V600E, NRAS, NF1 mutations, and triple-negative genotypes occurred in 6.9%, 30.1%, 17.8%, 32.9%, and 12.3% of patients, respectively. Median potential follow-up was 41.0 months. Patients with BRAF fusion/rearrangement had decreased progression-free and overall survival (p = 0.015). The other genotypes each had similar progression-free and overall survival. Patients who achieved a complete best objective response at 12 months (n = 36, 49.3%) were found to have significantly improved survival compared those who failed to achieve remissions (n = 37, 50.7%, p < 0.001). Conclusions: The most important determinant of long-term survival was achievement of a complete response by 12 months following immunotherapy. PR and SD were not a stable type of response and generally resulted in progression and death from melanoma. Rare patients with BRAF fusions or rearrangements had decreased progression-free and overall survival following initial immunotherapy. Other BRAF, NRAS, or NF1 mutations were not associated with significant differences in outcome.
What Is the Significance of Indeterminate Pulmonary Nodules in High-Grade Soft Tissue Sarcomas? A Retrospective Cohort Study
Authors: Brookes Marcus J. , Chan Corey D. , Crowley Timothy P. , Ragbir Maniram , Beckingsale Thomas , Ghosh Kanishka M. , Rankin Kenneth S.
Published: July 2023

Background: Sarcomas are rare, aggressive cancers which frequently metastasise to the lungs. Following diagnosis, patients typically undergo staging by means of a CT scan of their chest. This often identifies indeterminate pulmonary nodules (IPNs), but the significance of these in high-grade soft tissue sarcoma (STS) is unclear. Identifying whether these are benign or malignant is important for clinical decision making. This study analyses the clinical relevance of IPNs in high-grade STS. Methods: All patients treated at our centre for high-grade soft tissue sarcoma between 2010 and 2020 were identified from a prospective database. CT scans and their reports were reviewed, and survival data were collected from patient records. Results: 389 suitable patients were identified; 34.4% had IPNs on their CT staging scan and 20.1% progressed into lung metastases. Progression was more likely with IPNs ≥ 5 mm in diameter (p = 0.006), multiple IPNs (p = 0.013) or bilateral IPNs (p = 0.022), as well as in patients with primaries ≥ 5 cm (p = 0.014), grade 3 primaries (p = 0.009) or primaries arising deep to the fascia (p = 0.041). The median time to progression was 143 days. IPNs at diagnosis were associated with an increased risk of developing lung metastases and decreased OS in patients with grade 3 STS (p = 0.0019 and p = 0.0016, respectively); this was not observed in grade 2 patients. Conclusions: IPNs at diagnosis are associated with significantly worse OS in patients with grade 3 STS. It is crucial to consider the primary tumour as well as the IPNs when considering the risk of progression. Surveillance CT scans should be carried out within 6 months.
Cell-Free DNA Extracted from CSF for the Molecular Diagnosis of Pediatric Embryonal Brain Tumors
Authors: Chicard Mathieu , Iddir Yasmine , Masliah Planchon Julien , Combaret Valérie , Attignon Valéry , Saint-Charles Alexandra , Frappaz Didier , Faure-Conter Cécile , Beccaria Kévin , Varlet Pascale , Geoerger Birgit , Baulande Sylvain , Pierron Gaelle , Bouchoucha Yassine , Doz François , Delattre Olivier , Waterfall Joshua J. , Bourdeaut Franck , Schleiermacher Gudrun
Published: July 2023

Background: Liquid biopsies are revolutionary tools used to detect tumor-specific genetic alterations in body fluids, including the use of cell-free DNA (cfDNA) for molecular diagnosis in cancer patients. In brain tumors, cerebrospinal fluid (CSF) cfDNA might be more informative than plasma cfDNA. Here, we assess the use of CSF cfDNA in pediatric embryonal brain tumors (EBT) for molecular diagnosis. Methods: The CSF cfDNA of pediatric patients with medulloblastoma (n = 18), ATRT (n = 3), ETMR (n = 1), CNS NB FOXR2 (n = 2) and pediatric EBT NOS (n = 1) (mean cfDNA concentration 48 ng/mL; range 4–442 ng/mL) and matched tumor genomic DNA were sequenced by WES and/or a targeted sequencing approach to determine single-nucleotide variations (SNVs) and copy number alterations (CNA). A specific capture covering transcription start sites (TSS) of genes of interest was also used for nucleosome footprinting in CSF cfDNA. Results: 15/25 CSF cfDNA samples yielded informative results, with informative CNA and SNVs in 11 and 15 cases, respectively. For cases with paired tumor and CSF cfDNA WES (n = 15), a mean of 83 (range 1–160) shared SNVs were observed, including SNVs in classical medulloblastoma genes such as SMO and KMT2D. Interestingly, tumor-specific SNVs (mean 18; range 1–62) or CSF-specific SNVs (mean 5; range 0–25) were also observed, suggesting clonal heterogeneity. The TSS panel resulted in differential coverage profiles across all 112 studied genes in 7 cases, indicating distinct promoter accessibility. Conclusion: CSF cfDNA sequencing yielded informative results in 60% (15/25) of all cases, with informative results in 83% (15/18) of all cases analyzed by WES. These results pave the way for the implementation of these novel approaches for molecular diagnosis and minimal residual disease monitoring.
The Promise of Retinoids in the Treatment of Cancer: Neither Burnt Out Nor Fading Away
Authors: Nagai Yuya , Ambinder Alexander J.
Published: July 2023

Since the introduction of all-trans retinoic acid (ATRA), acute promyelocytic leukemia (APL) has become a highly curable malignancy, especially in combination with arsenic trioxide (ATO). ATRA’s success has deepened our understanding of the role of the RARα pathway in normal hematopoiesis and leukemogenesis, and it has influenced a generation of cancer drug development. Retinoids have also demonstrated some efficacy in a handful of other disease entities, including as a maintenance therapy for neuroblastoma and in the treatment of cutaneous T-cell lymphomas; nevertheless, the promise of retinoids as a differentiating therapy in acute myeloid leukemia (AML) more broadly, and as a cancer preventative, have largely gone unfulfilled. Recent research into the mechanisms of ATRA resistance and the biomarkers of RARα pathway dysregulation in AML have reinvigorated efforts to successfully deploy retinoid therapy in a broader subset of myeloid malignancies. Recent studies have demonstrated that the bone marrow environment is highly protected from exogenous ATRA via local homeostasis controlled by stromal cells expressing CYP26, a key enzyme responsible for ATRA inactivation. Synthetic CYP26-resistant retinoids such as tamibarotene bypass this stromal protection and have shown superior anti-leukemic effects. Furthermore, recent super-enhancer (SE) analysis has identified a novel AML subgroup characterized by high expression of RARα through strong SE levels in the gene locus and increased sensitivity to tamibarotene. Combined with a hypomethylating agent, synthetic retinoids have shown synergistic anti-leukemic effects in non-APL AML preclinical models and are now being studied in phase II and III clinical trials.
Preoperative CT-Based Skeletal Muscle Mass Depletion and Outcomes after Total Laryngectomy
Authors: Salati Victoria , Mandralis Katerina , Becce Fabio , Koerfer Joachim , Lambercy Karma , Simon Christian , Gorostidi François
Published: July 2023

Purpose: To assess the role of preoperative CT-based skeletal muscle mass depletion on postoperative clinical outcomes and survival in patients who underwent total laryngectomy for cancer. Methods: Patients operated on between January 2011 and March 2020 were retrospectively included. Skeletal muscle area and intra- and inter-muscular fat accumulation were measured at the third lumbar vertebral level on preoperative CT scans. Skeletal muscle mass depletion was defined based on pre-established cut-off values. Their association with postoperative morbidity, length of stay (LOS), costs, and survival was assessed. Results: A total of 84 patients were included, of which 37 (44%) had preoperative skeletal muscle mass depletion. The rate of postoperative fistula (23% vs. 35%, p = 0.348), cutaneous cervical dehiscence (17% vs. 11%, p = 0.629), superficial incisional surgical site infections (SSI) (12% vs. 10%, p = 1.000), and unplanned reoperation (38% vs. 37%, p = 1.000) were comparable between the two patient groups. No difference in median LOS was observed (41 vs. 33 days, p = 0.295), nor in treatment costs (119,976 vs. 109,402 CHF, p = 0.585). The median overall survival was comparable between the two groups (3.43 vs. 4.95 years, p = 0.09). Conclusions: Skeletal muscle mass depletion alone had no significant impact on postoperative clinical outcomes or survival.
Application of Radiomics in Prognosing Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis
Authors: Wang Ting-Wei , Hsu Ming-Sheng , Lin Yi-Hui , Chiu Hwa-Yen , Chao Heng-Sheng , Liao Chien-Yi , Lu Chia-Feng , Wu Yu-Te , Huang Jing-Wen , Chen Yuh-Min
Published: July 2023

In the context of non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs), this research evaluated the prognostic value of CT-based radiomics. A comprehensive systematic review and meta-analysis of studies up to April 2023, which included 3111 patients, was conducted. We utilized the Quality in Prognosis Studies (QUIPS) tool and radiomics quality scoring (RQS) system to assess the quality of the included studies. Our analysis revealed a pooled hazard ratio for progression-free survival of 2.80 (95% confidence interval: 1.87–4.19), suggesting that patients with certain radiomics features had a significantly higher risk of disease progression. Additionally, we calculated the pooled Harrell’s concordance index and area under the curve (AUC) values of 0.71 and 0.73, respectively, indicating good predictive performance of radiomics. Despite these promising results, further studies with consistent and robust protocols are needed to confirm the prognostic role of radiomics in NSCLC.
Contrast-Enhanced Liver Magnetic Resonance Image Synthesis Using Gradient Regularized Multi-Modal Multi-Discrimination Sparse Attention Fusion GAN
Authors: Jiao Changzhe , Ling Diane , Bian Shelly , Vassantachart April , Cheng Karen , Mehta Shahil , Lock Derrick , Zhu Zhenyu , Feng Mary , Thomas Horatio , Scholey Jessica E. , Sheng Ke , Fan Zhaoyang , Yang Wensha
Published: July 2023

Purposes: To provide abdominal contrast-enhanced MR image synthesis, we developed an gradient regularized multi-modal multi-discrimination sparse attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. Methods: With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean squared error (MSE). A Turing test and experts’ contours evaluated the image synthesis quality. Results: The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values < 0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, which is close to random guessing, supporting the model’s effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90 compared to the inter-operator DICE of 0.91. Conclusion: We demonstrated the function of a novel multi-modal MR image synthesis neural network GRMM-GAN for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.
The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican
Authors: Berdiaki Aikaterini , Giatagana Eirini-Maria , Tzanakakis George , Nikitovic Dragana
Published: July 2023

Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment contains tumor cells, non-malignant cells, blood vessels, cells of the immune system, stromal cells, and the extracellular matrix (ECM). The small leucine-rich proteoglycans (SLRPs) are a family of nineteen proteoglycans, which are ubiquitously expressed among mammalian tissues and especially abundant in the ECM. SLRPs are divided into five canonical classes (classes I–III, containing fourteen members) and non-canonical classes (classes IV–V, including five members) based on their amino-acid structural sequence, chromosomal organization, and functional properties. Variations in both the protein core structure and glycosylation status lead to SLRP-specific interactions with cell membrane receptors, cytokines, growth factors, and structural ECM molecules. SLRPs have been implicated in the regulation of cancer growth, motility, and invasion, as well as in cancer-associated inflammation and autophagy, highlighting their crucial role in the processes of carcinogenesis. Except for the class I SLRP decorin, to which an anti-tumorigenic role has been attributed, other SLPRs’ roles have not been fully clarified. This review will focus on the functions of the class I and II SLRP members biglycan and lumican, which are correlated to various aspects of cancer development.
Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Gogate Anagha , Bennett Bryan , Poonja Zia , Stewart Grant , Medina Colmenero Ana , Szturz Petr , Carrington Courtney , Castro Clara , Gemmen Eric , Lau Ashley , Carral Maseda Alberto , Winquist Eric , Arrazubi Virginia , Hao Desiree , Cook Audrey , Martinez Galan Joaquina , Ugidos Lisardo , Fernández Garay David , Gutierrez Abad David , Metcalf Robert
Published: July 2023

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as ‘partial response’, with 3.9% reporting ‘complete response’. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients.
Functional Diversity of Novel Lectins with Unique Structural Features in Marine Animals
Authors: Hatakeyama Tomomitsu , Unno Hideaki
Published: July 2023

Due to their remarkable structural diversity, glycans play important roles as recognition molecules on cell surfaces of living organisms. Carbohydrates exist in numerous isomeric forms and can adopt diverse structures through various branching patterns. Despite their relatively small molecular weights, they exhibit extensive structural diversity. On the other hand, lectins, also known as carbohydrate-binding proteins, not only recognize and bind to the diverse structures of glycans but also induce various biological reactions based on structural differences. Initially discovered as hemagglutinins in plant seeds, lectins have been found to play significant roles in cell recognition processes in higher vertebrates. However, our understanding of lectins in marine animals, particularly marine invertebrates, remains limited. Recent studies have revealed that marine animals possess novel lectins with unique structures and glycan recognition mechanisms not observed in known lectins. Of particular interest is their role as pattern recognition molecules in the innate immune system, where they recognize the glycan structures of pathogens. Furthermore, lectins serve as toxins for self-defense against foreign enemies. Recent discoveries have identified various pore-forming proteins containing lectin domains in fish venoms and skins. These proteins utilize lectin domains to bind target cells, triggering oligomerization and pore formation in the cell membrane. These findings have spurred research into the new functions of lectins and lectin domains. In this review, we present recent findings on the diverse structures and functions of lectins in marine animals.
Synergism between Graphene and Molecularly Imprinted Polymers in Developing Electrochemical Sensors for Agri-Food and Environmental Analyses
Authors: Radu Gabriel-Lucian , Lițescu Simona Carmen , Enache Alin , Albu Camelia , Eremia Sandra A. V.
Published: July 2023

In recent years, new sensor-based technologies have been developed to meet the demand for rapid and accurate analysis of food and environment, as food safety and environmental monitoring are very important concerns nowadays. In this context, considerable attention has been paid to the development and design of electrochemical sensors, as these offer a number of advantages, such as portability, ease of use, low costs and fast response times. Molecularly imprinted polymers (MIPs) are robust synthetic polymers with special cavities designed for a target molecule, and they are used as selective tools through a mechanism of molecular recognition. Graphene is a 2D crystalline carbon that forms either a single or a coupled layer of hexagonally arranged carbon atoms and is referred to as a “wonder material”. The use of these two structures in the development of electrochemical sensors gives the newly created analytical tool enhanced properties, such as improved sensitivity and selectivity, low detection limit, good stability and reusability. This review presents an overview of the recent research regarding the use of MIPs and graphene in the development of electrochemical sensors for food and environmental analyses, critically discusses the pros and cons, and gives perspectives for further developments in this field.
Relationship between Sensory Processing Skills and Feeding Behaviors in Children Aged 3–6 Years with Cerebral Palsy with Cerebral Visual Impairment
Authors: Cemali Mustafa , Cemali Özge , Günal Ayla , Pekçetin Serkan
Published: July 2023

The current study aimed to examine the relationship between sensory processing skills and feeding behavior in cerebral palsy (CP) children aged 3–6 years with cerebral visual impairment (CVI). A total of ninety mothers participated in the study in three groups: thirty mothers of children with CP with CVI, thirty mothers of children with CP without CVI, and thirty mothers of children with typical development (TD). The sensory processing skill of the children was evaluated with the Sensory Profile (SP), and feeding behavior was evaluated with the the Behavioral Pediatric Feeding Assessment Scale (BPFAS). In the triple comparison, a significant difference was found between the groups in all SP parameter and BPFAS scores (p < 0.001). Post hoc analysis revealed statistically significant differences between the groups in all parameters (p < 0.001). Feeding problems were detected in 65% of all groups. In the correlation analysis, a significant relationship was found between all parameters of the SP and the BPFAS (p < 0.05). In terms of sensory processing skills and feeding status, it was determined that children with CVI with CP had more problems than children with CP without CVI, and children with CP without CVI had more problems than children with TD. With these results, it was concluded that sensory processing problems affect feeding status, and visual impairment causes both sensory problems and feeding problems.
Behavioral and Sleep Disorders in Children and Adolescents following COVID-19 Disease: A Case-Control Study
Authors: Miraglia del Giudice Michele , Klain Angela , Dinardo Giulio , D’Addio Elisabetta , Bencivenga Chiara Lucia , Fontanella Cristina , Decimo Fabio , Umano Giuseppina Rosaria , Siciliano Margherita , Carotenuto Marco , Indolfi Cristiana
Published: July 2023

Introduction: Recent studies show that neuropsychiatric disorders are the most frequent sequelae of COVID-19 in children. Purpose: Our work aimed to evaluate the impact of SARS-CoV-2 infection on behavior and sleep in children and adolescents. Materials and Methods: We enrolled 107 patients aged 1.5–18 years who contracted COVID-19 between one year and one month prior to data collection, referred to the University of Campania Luigi Vanvitelli in Italy. We asked their parents to complete two standardized questionnaires for the assessment of behavior (Child Behavior CheckList (CBCL)) and sleep (Sleep Disturbance Scale for Children (SLDS)). We analysed and compared the results with a control group (pre-COVID-19 pandemic). Results: In the COVID-19 group, the major results were found for sleep breathing disorders, sleep–wake transition disorders and disorders of initiating and maintaining sleep for the SDSC questionnaire, and internalizing scale, total scale and anxiety/depression for the CBCL questionnaire. The comparison of the CBCL results of the cases with the controls revealed statistically significant differences for the following items: internalizing scale, externalizing scale, somatic complaints, total score, thought problems [(p < 0.01)], anxious/depressed problems and withdrawn [(p < 0.001)]. Conclusions: COVID-19 has impacted children’s and adolescents’ mental health. Adolescents were the most affected patient group for internalizing problems, including anxiety and depression.
Knowledge, Attitudes and Practices Regarding Taeniasis in Pakistan
Authors: Bibi Saba , Kamran Muhammad , Ahmad Haroon , Bibi Kainat , Naqvi Syed Kamran Ul Hassan , Zuo Qingqiu , Shah Naseer Ali , Cao Jianping
Published: July 2023

Taeniasis is a neglected zoonotic disease responsible for serious health disorders, such as seizures, and may even cause death. Humans are the definitive host for the three species Taenia solium (pork tapeworm), T. saginata (beef tapeworm), and T. asiatica, harboring the adult tapeworm in the small intestine. In this study, a structured questionnaire was circulated to assess the knowledge, attitudes, and practices (KAPs) regarding taeniasis among the rural and urban communities of Rawalpindi and Islamabad, Pakistan. A total of 770 individuals participated in the study. Of the total respondents, 44.4% had little knowledge about the disease and its impact, while the majority (70%) of respondents showed a willingness to participate in elimination campaigns by providing fecal samples. Most respondents kept raw meat separated from clean utensils (81.6%) and checked the internal temperature of meat when cooking it (75.1%). Regression analysis showed a significant association between age and knowledge, especially in the 20–30 years (p < 0.05; OR 0.574) and 30 to 40 years (p < 0.05; OR 0.553) age groups, and being a resident in Rawalpindi (p < 0.05; OR 0.68) and other cities (p < 0.05; OR 2.43), except Islamabad. Income ranges of 31,000–50,000 PKR (p < 0.05; OR: 0.574), 51,000–70,000 PKR (p < 0.05; OR 0.531), and above 70,000 PKR (p < 0.05; OR 0.42) were significantly related to attitude, compared with individuals with incomes of 10,000–30,000 PKR. Income above 70,000 PKR (p < 0.05; OR 0.87) and living in an urban area (p < 0.05; OR 0.616) compared to a rural area were significant with practices. A positive attitude was observed regarding awareness and prevention of the disease. Awareness campaigns and providing health education could be key approaches to manage this disease in the general population of developing countries.
Kernel-Free Quadratic Surface Support Vector Regression with Non-Negative Constraints
Authors: Wei Dong , Yang Zhixia , Ye Junyou , Yang Xue
Published: July 2023

In this paper, a kernel-free quadratic surface support vector regression with non-negative constraints (NQSSVR) is proposed for the regression problem. The task of the NQSSVR is to find a quadratic function as a regression function. By utilizing the quadratic surface kernel-free technique, the model avoids the difficulty of choosing the kernel function and corresponding parameters, and has interpretability to a certain extent. In fact, data may have a priori information that the value of the response variable will increase as the explanatory variable grows in a non-negative interval. Moreover, in order to ensure that the regression function is monotonically increasing on the non-negative interval, the non-negative constraints with respect to the regression coefficients are introduced to construct the optimization problem of NQSSVR. And the regression function obtained by NQSSVR matches this a priori information, which has been proven in the theoretical analysis. In addition, the existence and uniqueness of the solution to the primal problem and dual problem of NQSSVR, and the relationship between them are addressed. Experimental results on two artificial datasets and seven benchmark datasets validate the feasibility and effectiveness of our approach. Finally, the effectiveness of our method is verified by real examples in air quality.