bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic Therapy Effects on Oral Dysplastic Keratinocyte Cell Cultures: A Systematic Review
Authors: Di Stasio Dario , Romano Antonio , Fiori Fausto , Assanti Remo Antonio , Ruocco Eleonora , Bottone Maria Grazia , Lucchese Alberta
Published: August 2023

Photodynamic therapy (PDT) represents a therapeutic intervention applied in various pre-malignant and malignant disorders’ treatments. The interaction between a photosensitizer (PS), ideal wavelength radiation, and tissue molecular oxygen activates a series of photochemical reactions liable to produce reactive oxygen species. These highly reactive species allow for the decrease cell proliferation and yield cancerous and pre-cancerous cell death. The aim of this work is to carry out a systematic review to investigate the effects of in vitro PDT for oral potential malignant disorders (OPDM) cell lines. This systematic review was conducted according to the PRISMA protocol, and the PROSPERO registration number was CRD42022362349. An electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. The Population, Intervention, Comparison, Outcomes, and Study design (PICOS) has been applied as the method by which to outline our study eligibility criteria. The QUIN tool was employed to interpret the risk of bias of the included studies. Initially, seventy-five records were retrieved through databases, and after the selection steps, seven items finally met our inclusion criteria. The preliminary search resulted in 75 studies, out of which 22 were found to be duplicates. After reviewing the titles and abstracts of the remaining 53 studies, 45 were rejected as they did not meet the inclusion criteria. Further evaluation of the full texts led to the exclusion of only one article, since the full text was not available. As a result, seven studies were ultimately identified and included in the analysis. The main findings confirm the role of in vitro photodynamic therapy using several photosensitizers as a potential treatment for oral potentially malignant disorders.
Opportunistic Pathogens Isolated from Peri-Implant and Periodontal Subgingival Plaque from Adjacent Teeth
Authors: Sá Ana Maísa , Mendes José Manuel , Silva António Sérgio , Gonçalves Maria dos Prazeres , Cardoso Mónica , Coelho Cristina
Published: August 2023

Even though most studies consider strict anaerobe Gram-negative bacteria as the main factor associated with peri-implantitis, other studies have identified other microorganisms present in implants related to peri-implant disease that have the ability to reduce the effectiveness of treatment, such as Candida spp., Enterococcus faecalis and Pseudomonas aeruginosa. Therefore, microbiologic diagnosis is important for the success of implant treatment. The main goal of this study was to detect Candida spp., E. faecalis and P. aeruginosa in the peri-implant and periodontal subgingival plaque in the presence or absence of disease and to relate the presence of these microorganisms with demographic data, hygiene habits, the type of implant connection and endodontic treatment. The study population consisted of 20 patients that filled out a questionnaire regarding gender, age, systemic diseases and oral hygiene. The peri-implant and periodontal subgingival plaque from an adjacent tooth, both with and without disease, were analysed for the presence of these three opportunistic pathogens. Microbiological analysis revealed a higher prevalence of E. faecalis in patients with and without periodontal and peri-implant disease. Candida spp. was identified in a higher degree in cases with disease, and P. aeruginosa was mostly detected in peri-implantitis. The detection of these three pathogens suggested a possible means of transmission of infection from adjacent teeth to implants, with the implant design associated with rehabilitation being a primary cause of pathogen growth. Although this study did not relate pathogen growth directly to periodontal disease, the high colony forming unit per millilitre (CFU/mL) values of E. faecalis may reveal an aetiological role of this bacterium in peri-implantitis.
Experimental and Numerical Study of the Performance of an Open-Type Multi-Deck Refrigerated Cabinet with Single and Dual Air Curtain
Authors: Vengalis Tadas , Mokšin Vadim
Published: August 2023

This study utilizes a simplified two-dimensional time-dependent computational fluid dynamic (CFD) model to compare the performance of single- and two-layer air curtains in an open-type multi-deck refrigerated display cabinet. Two layers of air curtain generate a more effective invisible barrier from ambient air impact that can reduce electrical energy consumption and maintain a uniform temperature distribution within the cabinet. The CFD model of a refrigerated display cabinet was validated by the experimental data. The results showed a two-layer air curtain advantage over a single air curtain. Electrical energy consumption decreased by 18.5%, and the average temperature of the test products decreased from 5.75 °C to 5.17 °C. The results obtained are important for cabinet design to improve the quality of product storage and reduce energy consumption.
Development of Prediction Models for the Pasting Parameters of Rice Based on Near-Infrared and Machine Learning Tools
Authors: Sampaio Pedro Sousa , Carbas Bruna , Brites Carla
Published: August 2023

Due to the importance of rice (Oryza sativa) in food products, developing strategies to evaluate its quality based on a fast and reliable methodology is fundamental. Herein, near-infrared (NIR) spectroscopy combined with machine learning algorithms, such as interval partial least squares (iPLS), synergy interval PLS (siPLS), and artificial neural networks (ANNs), allowed for the development of prediction models of pasting parameters, such as the breakdown (BD), final viscosity (FV), pasting viscosity (PV), setback (ST), and trough (TR), from 166 rice samples. The models developed using iPLS and siPLS were characterized, respectively, by the following regression values: BD (R = 0.84; R = 0.88); FV (R = 0.57; R = 0.64); PV (R = 0.85; R = 0.90); ST (R = 0.85; R = 0.88); and TR (R = 0.85; R = 0.84). Meanwhile, ANN was also tested and allowed for a significant improvement in the models, characterized by the following values corresponding to the calibration and testing procedures: BD (Rcal = 0.99; Rtest = 0.70), FV (Rcal = 0.99; Rtest = 0.85), PV (Rcal = 0.99; Rtest = 0.80), ST (Rcal = 0.99; Rtest = 0.76), and TR (Rcal = 0.99; Rtest = 0.72). Each model was characterized by a specific spectral region that presented significative influence in terms of the pasting parameters. The machine learning models developed for these pasting parameters represent a significant tool for rice quality evaluation and will have an important influence on the rice value chain, since breeding programs focus on the evaluation of rice quality.
Enhancing Cloud Computing Analysis: A CCE-Based HTTP-GET Log Dataset
Authors: Alashhab Ziyad R. , Anbar Mohammed , Rihan Shaza Dawood Ahmed , Alabsi Basim Ahmad , Ateeq Karamath
Published: August 2023

The Hypertext Transfer Protocol (HTTP) is a common target of distributed denial-of-service (DDoS) attacks in today’s cloud computing environment (CCE). However, most existing datasets for Intrusion Detection System (IDS) evaluations are not suitable for CCEs. They are either self-generated or are not representative of CCEs, leading to high false alarm rates when used in real CCEs. Moreover, many datasets are inaccessible due to privacy and copyright issues. Therefore, we propose a publicly available benchmark dataset of HTTP-GET flood DDoS attacks on CCEs based on an actual private CCE. The proposed dataset has two advantages: (1) it uses CCE-based features, and (2) it meets the criteria for trustworthy and valid datasets. These advantages enable reliable IDS evaluations, tuning, and comparisons. Furthermore, the dataset includes both internal and external HTTP-GET flood DDoS attacks on CCEs. This dataset can facilitate research in the field and enhance CCE security against DDoS attacks.
Development of Inclined Applicators for Flattened Beam Intraoperative Radiotherapy
Authors: Kim Jeong Heon , Ahn Sohyun , Park Kwangwoo , Lee Rena , Kim Jin Sung
Published: August 2023

A 3D-printed applicator for intraoperative radiation therapy (IORT) using the INTRABEAM system has been introduced, designed to protect normal tissue, expand indications, and assess its effectiveness in various intraoperative settings. The study involved designing and creating inclined applicators at 0° and 45° angles, which were capable of producing flattened and unflattened beams and shielding non-target areas from radiation. The applicator was evaluated based on dose uniformity, percentage depth dose, leakage, and dose rate. The findings showed that the applicator provided a uniform beam at various depths (1.23 to 1.30 for the flattened beam and 1.25 to 1.32 for the unflattened beam) and effectively shielded against leakage, with no leakage dose measured at 1 mm from the surface. Additionally, the dose rates after 3 min of irradiation for flattened and unflattened beams were 51.0 and 52.9 cGy for 0° and 48.5 and 54.8 cGy for 45° applicators, respectively. This suggests that the applicator can efficiently deliver IORT while minimizing exposure to normal tissues, particularly in treating chest and abdominal lesions near or on critical organs. The applicator has undergone dose calibration and has moved forward to clinical application.
Unsupervised Learning-Based Spectrum Sensing Algorithm with Defending Adversarial Attacks
Authors: Li Xinyu , Dai Shaogang , Zhao Zhijin
Published: August 2023

Although the spectrum sensing algorithms based on deep learning have achieved remarkable detection performance, the sensing performance is easily affected by adversarial attacks due to the fragility of neural networks. Even slight adversarial perturbations lead to a sharp deterioration of the model detection performance. To enhance the defense capability of the spectrum sensing model against such attacks, an unsupervised learning-based spectrum sensing algorithm with defending adversarial attacks (USDAA) is proposed, which is divided into two stages: adversarial pre-training and fine-tuning. In the adversarial pre-training stage, encoders are used to extract the features of adversarial samples and clean samples, respectively, and then decoders are used to reconstruct the samples, and comparison loss and reconstruction loss are designed to optimize the network parameters. It can reduce the dependence of model training on labeled samples and improve the robustness of the model to attack perturbations. In the fine-tuning stage, a small number of adversarial samples are used to fine-tune the pre-trained encoder and classification layer to obtain the spectrum sensing defense model. The experimental results show that the USDAA algorithm is better than the denoising autoencoder and distillation defense algorithm (DAED) against FGSM and PGD adversarial attacks. The number of labeled samples used in USDAA is only 11% of the DAED. When the false alarm probability is 0.1 and the SNR is −10 dB, the detection probability of the USDAA algorithm for the fast gradient sign method (FGSM) and the projected gradient descent (PGD) attack samples with random perturbations is above 88%, while the detection probability of the DAED algorithm for both attack samples is lower than 69%. Additionally, the USDAA algorithm has better robustness to attack with unknown perturbations.
A Machine Learning-Based Model to Predict In-Hospital Mortality of Lung Cancer Patients: A Population-Based Study of 523,959 Cases
Authors: Tran Que N. N. , Le Minh-Khang , Kondo Tetsuo , Moriguchi Takeshi
Published: August 2023

Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training (n = 115,145) and validation datasets (n = 13,017). The remaining cohort with missing values (n = 394,779) was then combined with the primary lung tumour datasets (n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78–0.79) and 0.78 (95%CI = 0.77–0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757–0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning.
Agricultural Water Deficit Trends in Yemen
Authors: Gadain Hussein , Libanda Brigadier
Published: August 2023

Globally, climate change is triggering shifts in water availability, especially across arid and desert landscapes similar to that in Yemen, where precipitation patterns are increasingly erratic. Here, we use water budget calculations, drought metrics, and trend analyses to examine climatic water deficits, with the aim of unraveling irrigation demands and overall water stress across Yemen. The results indicate that 94% of the influx is lost back to the atmosphere via evapotranspiration, 6% is converted to runoff, and only a negligible amount, generally less than 1%, is retained as storage. The results also show an unrelenting, statistically significant water deficit increase of 0.17 mm yr−1 on the Sen’s slope, at the critical Z-value of 0.005 across the country, for the past 63 years. Our findings challenge the conventional understanding of water deficits across Yemen and suggest that the country’s water resources situation is direr than was earlier documented. Further results show that while the water shortage mosaic across the country experiences interannual variations, their occurrence is significantly intensifying. As such, an immediate and radical modernization of integrated water management systems, including concerted investments in irrigation and artificial recharge wells, especially across the Arabian Sea Coast, the Red Sea Coast, and the Highlands, is strongly recommended.
Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study)
Authors: Pluskiewicz Wojciech , Adamczyk Piotr , Werner Aleksandra , Bach Małgorzata , Drozdzowska Bogna
Published: August 2023

Background. The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. Methods. The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. Results. Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of −1.86 ± 1.04 compared to −1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. Conclusions. Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.
Differences in Mortality and Sepsis-Associated Organ Dysfunction between Surgical and Non-Surgical Sepsis Patients
Authors: Mewes Caspar , Runzheimer Julius , Böhnke Carolin , Büttner Benedikt , Nemeth Marcus , Hinz José , Quintel Michael , Mansur Ashham
Published: August 2023

(1) Background: Patients with sepsis following surgical intervention may exhibit fundamental distinctions from those experiencing sepsis without prior surgery. Despite the potential clinical importance of distinguishing these two sepsis subpopulations, dissimilarities, particularly in outcome, between surgical and non-surgical patients have been subject to limited scientific investigations in the existing literature. This study aimed to investigate the differences in mortality and sepsis-associated organ dysfunction between these two groups. (2) Methods: A retrospective analysis was conducted using data from a large cohort of prospectively enrolled patients with sepsis (n = 737) admitted to three intensive care units at University Medical Center Goettingen; patients were categorized into surgical (n = 582) and non-surgical sepsis groups (n = 155). The primary outcomes assessed were 28- and 90-day mortality rates, and secondary endpoints were multiple clinical parameters and measures of sepsis-associated organ dysfunction. (3) Results: Non-surgical patients presented a significantly higher 90-day mortality (37%) compared to surgical sepsis patients (30%, p = 0.0457). Moreover, the non-surgical sepsis group exhibited increased sepsis-associated organ dysfunction, as evidenced by higher average SOFA scores (p < 0.001), elevated levels of serum Procalcitonin (p = 0.0102), and a higher utilization of organ replacement therapies such as ventilation (p < 0.001), vasopressor treatment (p < 0.001), and renal replacement therapy (p = 0.0364). Additionally, non-surgical sepsis patients had higher organ-specific SOFA respiratory (p < 0.001), cardiovascular (p < 0.001), renal (p < 0.001), coagulation (0.0335), and central nervous system (p = 0.0206) subscores. (4) Conclusions: These results suggested that patients with non-surgical sepsis may face distinct challenges and a higher risk of adverse outcomes compared to patients with sepsis following surgical intervention. These findings have important implications for clinical decision-making, patient management, and resource allocation in sepsis care.
The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress—Role of New Drugs, Flozins
Authors: Bodnar Patryk , Mazurkiewicz Michalina , Chwalba Tomasz , Romuk Ewa , Ciszek-Chwalba Anna , Jacheć Wojciech , Wojciechowska Celina
Published: August 2023

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation–reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors—an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.
Prediction of Visual Acuity in Pathologic Myopia with Myopic Choroidal Neovascularization Treated with Anti-Vascular Endothelial Growth Factor Using a Deep Neural Network Based on Optical Coherence Tomography Images
Authors: Yang Migyeong , Han Jinyoung , Park Ji In , Hwang Joon Seo , Han Jeong Mo , Yoon Jeewoo , Choi Seong , Hwang Gyudeok , Hwang Daniel Duck-Jin
Published: August 2023

Myopic choroidal neovascularization (mCNV) is a common cause of vision loss in patients with pathological myopia. However, predicting the visual prognosis of patients with mCNV remains challenging. This study aimed to develop an artificial intelligence (AI) model to predict visual acuity (VA) in patients with mCNV. This study included 279 patients with mCNV at baseline; patient data were collected, including optical coherence tomography (OCT) images, VA, and demographic information. Two models were developed: one comprising horizontal/vertical OCT images (H/V cuts) and the second comprising 25 volume scan images. The coefficient of determination (R2) and root mean square error (RMSE) were computed to evaluate the performance of the trained network. The models achieved high performance in predicting VA after 1 (R2 = 0.911, RMSE = 0.151), 2 (R2 = 0.894, RMSE = 0.254), and 3 (R2 = 0.891, RMSE = 0.227) years. Using multiple-volume scanning, OCT images enhanced the performance of the models relative to using only H/V cuts. This study proposes AI models to predict VA in patients with mCNV. The models achieved high performance by incorporating the baseline VA, OCT images, and post-injection data. This model could assist in predicting the visual prognosis and evaluating treatment outcomes in patients with mCNV undergoing intravitreal anti-vascular endothelial growth factor therapy.
Tracking Control for a Lower Extremity Exoskeleton Based on Adaptive Dynamic Programing
Authors: Su Qiying , Pei Zhongcai , Tang Zhiyong
Published: August 2023

The utilization of lower extremity exoskeletons has witnessed a growing presence across diverse domains such as the military, medical treatment, and rehabilitation. This paper introduces a novel design of a lower extremity exoskeleton specifically tailored for individuals engaged in heavy object carrying tasks. The exoskeleton incorporates an impressive 12 degrees of freedom (DOF), with four of them being effectively controlled through hydraulic cylinders. To achieve optimal control of this intricate lower extremity exoskeleton system, the authors propose an adaptive dynamic programming (ADP) algorithm. Several crucial components are established to implement this control scheme. These include the formulation of the state equation for the lower extremity exoskeleton system, which is well-suited for the ADP algorithm. Additionally, a corresponding performance index function based on the tracking error is devised, along with the game algebraic Riccati equation. By employing the value iteration ADP scheme, the lower extremity exoskeleton demonstrates highly effective tracking control. This research not only highlights the potential of the proposed control approach but also showcases its ability to enhance the overall performance and functionality of lower extremity exoskeletons, particularly in scenarios involving heavy object carrying. Overall, this study contributes to the advancement of lower extremity exoskeleton technology and offers valuable insights into the application of ADP algorithms for achieving precise and efficient control in demanding tasks.
Mechanistic Elucidation of Nanomaterial-Enhanced First-Generation Biosensors Using Probe Voltammetry of an Enzymatic Reaction
Authors: Wemple Ann H. , Kaplan Jamie S. , Leopold Michael C.
Published: August 2023

The incorporation of nanomaterials (NMs) into biosensing schemes is a well-established strategy for gaining signal enhancement. With electrochemical biosensors, the enhanced performance achieved from using NMs is often attributed to the specific physical properties of the chosen nanocomponents, such as their high electronic conductivity, size-dependent functionality, and/or higher effective surface-to-volume ratios. First generation amperometric biosensing schemes, typically utilizing NMs in conjunction with immobilized enzyme and semi-permeable membranes, can possess complex sensing mechanisms that are difficult to study and challenging to understand beyond the observable signal enhancement. This study shows the use of an enzymatic reaction between xanthine (XAN) and xanthine oxidase (XOx), involving multiple electroactive species, as an electrochemical redox probe tool for ascertaining mechanistic information at and within the modified electrodes used as biosensors. Redox probing using components of this enzymatic reaction are demonstrated on two oft-employed biosensing approaches and commonly used NMs for modified electrodes: gold nanoparticle doped films and carbon nanotube interfaces. In both situations, the XAN metabolism voltammetry allows for a greater understanding of the functionality of the semipermeable membranes, the role of the NMs, and how the interplay between the two components creates signal enhancement.
Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM)
Authors: Detroit Marion , Collier Mathis , Beeker Nathanaël , Willems Lise , Decroocq Justine , Deau-Fischer Bénédicte , Vignon Marguerite , Birsen Rudy , Moufle Frederique , Leclaire Clément , Balladur Elisabeth , Deschamps Paul , Chauchet Adrien , Batista Rui , Limat Samuel , Treluyer Jean-Marc , Ricard Laure , Stocker Nicolas , Hermine Olivier , Choquet Sylvain , Morel Véronique , Metz Carole , Bouscary Didier , Kroemer Marie , Zerbit Jérémie
Published: August 2023

Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.
Preclinical Evaluation of the FGFR-Family Inhibitor Futibatinib for Pediatric Rhabdomyosarcoma
Authors: Wu Jerry T. , Cheuk Adam , Isanogle Kristine , Robinson Christina , Zhang Xiaohu , Ceribelli Michele , Beck Erin , Shinn Paul , Klumpp-Thomas Carleen , Wilson Kelli M. , McKnight Crystal , Itkin Zina , Sotome Hiroshi , Hirai Hiroshi , Calleja Elizabeth , Wacheck Volker , Gouker Brad , Peer Cody J. , Corvalan Natalia , Milewski David , Kim Yong Y. , Figg William D. , Edmondson Elijah F. , Thomas Craig J. , Difilippantonio Simone , Wei Jun S. , Khan Javed
Published: August 2023

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite decades of clinical trials, the overall survival rate for patients with relapsed and metastatic disease remains below 30%, underscoring the need for novel treatments. FGFR4, a receptor tyrosine kinase that is overexpressed in RMS and mutationally activated in 10% of cases, is a promising target for treatment. Here, we show that futibatinib, an irreversible pan-FGFR inhibitor, inhibits the growth of RMS cell lines in vitro by inhibiting phosphorylation of FGFR4 and its downstream targets. Moreover, we provide evidence that the combination of futibatinib with currently used chemotherapies such as irinotecan and vincristine has a synergistic effect against RMS in vitro. However, in RMS xenograft models, futibatinib monotherapy and combination treatment have limited efficacy in delaying tumor growth and prolonging survival. Moreover, limited efficacy is only observed in a PAX3-FOXO1 fusion-negative (FN) RMS cell line with mutationally activated FGFR4, whereas little or no efficacy is observed in PAX3-FOXO1 fusion-positive (FP) RMS cell lines with FGFR4 overexpression. Alternative treatment modalities such as combining futibatinib with other kinase inhibitors or targeting FGFR4 with CAR T cells or antibody-drug conjugate may be more effective than the approaches tested in this study.
Beyond the Frontline: A Triple-Line Approach of Thoracic Surgeons in Lung Cancer Management—State of the Art
Authors: Bottet Benjamin , Piton Nicolas , Selim Jean , Sarsam Matthieu , Guisier Florian , Baste Jean-Marc
Published: August 2023

Non-small cell lung cancer (NSCLC) is now described as an extremely heterogeneous disease in its clinical presentation, histology, molecular characteristics, and patient conditions. Over the past 20 years, the management of lung cancer has evolved with positive results. Immune checkpoint inhibitors have revolutionized the treatment landscape for NSCLC in both metastatic and locally advanced stages. The identification of molecular alterations in NSCLC has also allowed the development of targeted therapies, which provide better outcomes than chemotherapy in selected patients. However, patients usually develop acquired resistance to these treatments. On the other hand, thoracic surgery has progressed thanks to minimally invasive procedures, pre-habilitation and enhanced recovery after surgery. Moreover, within thoracic surgery, precision surgery considers the patient and his/her disease in their entirety to offer the best oncologic strategy. Surgeons support patients from pre-operative rehabilitation to surgery and beyond. They are involved in post-treatment follow-up and lung cancer recurrence. When conventional therapies are no longer effective, salvage surgery can be performed on selected patients.
The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix–Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids
Authors: Noh Ji-Min , Choi Seung-Cheol , Song Myeong-Hwa , Kim Kyung Seob , Jun Seongmin , Park Jae Hyoung , Kim Ju Hyeon , Kim Kyoungmi , Ko Tae Hee , Choi Jong-Il , Gim Jeong-An , Kim Jong-Hoon , Jang Yongjun , Park Yongdoo , Na Ji Eun , Rhyu Im Joo , Lim Do-Sun
Published: August 2023

The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM–integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFβ/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs.
Heater Topology Influence on the Functional Characteristics of Thin-Film Gas Sensors Made by MEMS-Silicon Technology
Authors: Gorokh Gennady , Taratyn Igor , Fiadosenka Uladzimir , Reutskaya Olga , Lozovenko Andrei
Published: August 2023

The design of the heater plays a decisive role in the energy consumption, sensitivity, and speed of chemical sensors. The paper analyzes various options for the topology of meander-type platinum heaters in chemical sensors fabricated on thin dielectric membranes using MEMS-silicon technology. Comprehensive studies of the heater’s current–voltage characteristics have been carried out, heating rates have been measured at various currents, experimental temperature characteristics for various meander topologies have been obtained, heater options have been determined, and optimal heat transfer processes are ensured at a low power consumption of about 20–25 mW. Sensors with an optimal heater topology based on a double dielectric membrane were fabricated according to the described technological process, and sensory responses to 0.5 vol.% CH4 and 0.2% C3H8 were studied. The obtained results showed good results and confirmed the need to choose the optimal heater topology when designing sensors for recording the given type of gas mixtures in a certain temperature range.
Parental Preferences for Expanded Newborn Screening: What Are the Limits?
Authors: Liang Nicole S. Y. , Watts-Dickens Abby , Chitayat David , Babul-Hirji Riyana , Chakraborty Pranesh , Hayeems Robin Z.
Published: August 2023

The use of next-generation sequencing technologies such as genomic sequencing in newborn screening (NBS) could enable the detection of a broader range of conditions. We explored parental preferences and attitudes towards screening for conditions for which varying types of treatment exist with a cross-sectional survey completed by 100 parents of newborns who received NBS in Ontario, Canada. The survey included four vignettes illustrative of hypothetical screening targets, followed by questions assessing parental attitudes. Chi-square tests were used to compare frequency distributions of preferences. Results show that most parents supported NBS for conditions for which only supportive interventions are available, but to a significantly lesser degree than those with disease-specific treatments (99% vs. 82–87%, p ≤ 0.01). For conditions without an effective treatment, the type of supportive care and age of onset of the condition did not significantly alter parent perceptions of risks and benefits. Parents are interested in expanded NBS for conditions with only supportive interventions in childhood, despite lower levels of perceived benefit for the child and greater anticipated anxiety from screen-positive results. These preferences suggest that the expansion of NBS may require ongoing deliberation of perceived benefits and risks and enhanced approaches to education, consent, and support.
Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency
Authors: Ibrahim Majitha , Gold Jessica , Woodall Alison , Yilmaz Berna , Gissen Paul , Stepien Karolina
Published: August 2023

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited disorder of the urea cycle and, in general, is transmitted as an X-linked recessive trait. Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia, which is a direct cause of brain damage and death. Patients with late-onset OTCD can develop symptoms from infancy to later childhood, adolescence or adulthood. Clinical manifestations of adults with OTCD vary in acuity. Clinical symptoms can be aggravated by metabolic stressors or the presence of a catabolic state, or due to increased demands upon the urea. A prompt diagnosis and relevant biochemical and genetic investigations allow the rapid introduction of the right treatment and prevent long-term complications and mortality. This narrative review outlines challenges in diagnosing and managing patients with late-onset OTCD.
An Optimized Approach for Serial Crystallography Using Chips
Authors: Galchenkova Marina , Rahmani Mashhour Aida , Reinke Patrick Y. A. , Günther Sebastian , Meyer Jan , Chapman Henry N. , Yefanov Oleksandr M.
Published: August 2023

Serial crystallography is a rapidly developing method for the determination of the structure of biomolecules at room temperature at near-atomic resolution from an ensemble of small crystals. Numerous advances in detectors, data analysis pipelines, sample delivery methods, and crystallization protocols expand the scope of structural biology to understand the fundamental processes that take place in living cells. Many experimental strategies for serial crystallography are in use, depending on the type and sizes of the crystals or other needs of the experiment. Such strategies should ideally minimize the wastage of samples or beamtime without compromising experimental goals. This paper proposes a way to optimize beamtime utilization in serial crystallography experiments that use fixed-target sample delivery methods, such as chips. The strategy involves two key steps. Firstly, a fast raster scan of the chip is performed to determine the positions of the crystals based on their diffraction. Subsequently, a rotational series is collected at each identified crystal position, covering a narrow range of chip orientations. This approach enables the exclusion of empty positions during data acquisition, resulting in significant savings in beam time utilization and a reduced volume of measured data.
Hydrogen-like Impurity States in β-Ga2O3/(AlxGa1−x)2O3 Core/Shell Nanostructures: Comparison between Nanorods and Nanotubes
Authors: Ha Sihua , Zhu Jun
Published: August 2023

The binding energy of an off-center hydrogen-like impurity in an ultra-wide band gap β-Ga2O3/(AlxGa1−x)2O3 core/shell nanostructure is studied using a variational method combined with a finite-difference algorithm. Four impurity states with the radial and axial quantum numbers being 0 or 1 in two kinds of core/shell nanostructures, including nanorods and double-walled nanotubes, are taken into account in the numerical calculations. The variation trends in binding energy corresponding to the four impurity states as functions of structural dimension and Al composition differ in nanorods and nanotubes when the impurity moves toward the interface between the Ga2O3 and (AlxGa1−x)2O3 layers. The quantum confinement due to the structural geometry has a considerable influence on the probability density of the impurity states as well as the impurity binding energy. The numerical results will pave the way toward theoretical simulation of the electron states in rapidly developing β-Ga2O3 low-dimensional material systems for optoelectronic device applications.
Corrosion of Eutectic High-Entropy Alloys: A Review
Authors: Li Kaiyang , Zhai Yunlong , Lai Minjie , Song Min , Zou Shanfang , Huang Guojie , Yaqoob Khurram , Wang Zhangwei , Zhang Naiqiang
Published: August 2023

High-entropy alloys (HEAs) are emerging as a new family of alloys with equal/near-equal amounts of constituting elements and outstanding properties. In particular, eutectic high-entropy alloys (EHEAs) with alternate lamella phases possess both high strength and ductility, offering the advantage of conquering the strength–ductility trade-off that could hardly be achieved by conventional alloys. While the mechanical behavior of EHEAs has been widely studied, the corrosion behavior is still not fully understood. Furthermore, the environment-induced degradation could largely decide the service life of EHEA as engineering alloys, and the eutectic structure may have a special influence on the corrosion process. This article systematically reviews the corrosion studies of EHEAs by pointing out the structural features of EHEAs, summarizing the general corrosion issues for EHEAs and identifying the specific corrosion performance of different EHEA systems. It is found that EHEAs feature micro-galvanic corrosion due to their eutectic crystal structure, and such a corrosion mode is further affected by testing time, heat treatment, temperature, and applied potential. All the corrosion-affecting factors are summarized, and future research directions are suggested, aiming at ensuring the wide engineering application of EHEAs with both high strength–ductility and corrosion resistance.
Possible Interactions between Invasive Caulerpa Taxa and Native Macrozoobenthos: The Case Study of Favignana Island
Authors: Mannino Anna Maria , Balistreri Paolo
Published: August 2023

Biological invasions are widely recognized as a major threat to native biodiversity, ecosystem functioning and services. Amongst the NIS recorded in the Mediterranean Sea, Chlorophyta species belonging to the genus Caulerpa (Caulerpa cylindracea, C. taxifolia and C. taxifolia var. distichophylla) have raised serious concerns due to their potential or ascertained impact on native benthic communities. During surveys carried out to monitor the occurrence and the coverage of Caulerpa species along the coasts of Favignana Island (Egadi Islands Marine Protected Area), we observed variations in C. cylindracea and C. taxifolia coverage and also some large invertebrates overgrown with thalli of both species.
Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: The Next Threat after Viral Hepatitis
Authors: Salaheldin Mohamed , Aly Heba , Lau Louis , Afify Shimaa , El-Kassas Mohamed
Published: August 2023

For many years, we have faced the complications of viral hepatitis and alcohol-related liver diseases such as cirrhosis, decompensation, portal hypertension, and hepatocellular carcinoma (HCC). Recently, we have seen a dynamic change in the field of hepatology. With the significant achievements in eradicating the hepatitis C virus by direct-acting antiviral agents and the rising epidemic of obesity, diabetes mellitus, and metabolic syndrome, there is a paradigm shift in the leading cause of liver cirrhosis and cancer to nonalcoholic fatty liver disease (NAFLD). Current data highlight the rapidly rising incidence of NAFLD-related HCC worldwide and expose the unseen part of the iceberg. In this review, we aim to update knowledge about the pathogenesis of NAFLD-induced HCC, surveillance difficulties, and promising disease markers. Molecular biomarkers, for example, may become a promising cornerstone for risk-stratified surveillance, early detection, and treatment selection for NAFLD-related HCC. Physicians can offer personalized and tailor-made clinical decisions for this unique patient subgroup.
Bridged-U-Net-ASPP-EVO and Deep Learning Optimization for Brain Tumor Segmentation
Authors: Yousef Rammah , Khan Shakir , Gupta Gaurav , Albahlal Bader M. , Alajlan Saad Abdullah , Ali Aleem
Published: August 2023

Brain tumor segmentation from Magnetic Resonance Images (MRI) is considered a big challenge due to the complexity of brain tumor tissues, and segmenting these tissues from the healthy tissues is an even more tedious challenge when manual segmentation is undertaken by radiologists. In this paper, we have presented an experimental approach to emphasize the impact and effectiveness of deep learning elements like optimizers and loss functions towards a deep learning optimal solution for brain tumor segmentation. We evaluated our performance results on the most popular brain tumor datasets (MICCAI BraTS 2020 and RSNA-ASNR-MICCAI BraTS 2021). Furthermore, a new Bridged U-Net-ASPP-EVO was introduced that exploits Atrous Spatial Pyramid Pooling to enhance capturing multi-scale information to help in segmenting different tumor sizes, Evolving Normalization layers, squeeze and excitation residual blocks, and the max-average pooling for down sampling. Two variants of this architecture were constructed (Bridged U-Net_ASPP_EVO v1 and Bridged U-Net_ASPP_EVO v2). The best results were achieved using these two models when compared with other state-of-the-art models; we have achieved average segmentation dice scores of 0.84, 0.85, and 0.91 from variant1, and 0.83, 0.86, and 0.92 from v2 for the Enhanced Tumor (ET), Tumor Core (TC), and Whole Tumor (WT) tumor sub-regions, respectively, in the BraTS 2021validation dataset.
A Mixture of Essential Oils from Three Cretan Aromatic Plants Inhibits SARS-CoV-2 Proliferation: A Proof-of-Concept Intervention Study in Ambulatory Patients
Authors: Lionis Christos , Petelos Elena , Linardakis Manolis , Diamantakis Athanasios , Symvoulakis Emmanouil , Karkana Maria-Nefeli , Kampa Marilena , Pirintsos Stergios A. , Sourvinos George , Castanas Elias
Published: August 2023

Introduction: The need for effective therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remained largely unmet. Previous work has shown that a combination of three aromatic plants’ essential oils (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticose Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care settings. Methods: A total of 69 adult patients were included in a clinical proof-of-concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention group and control group) during three study periods (IG2020, n=13, IG2021/22, n=25, and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture was administered daily for 14 days per os in the intervention group, while the control group received usual care. Results: The PoC study found that the number and frequency of general symptoms, including general fatigue, weakness, fever, and myalgia, decreased following CAPeo administration. By Day 7, the average presence (number) of symptoms decreased in comparison with Day 1 in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1), representing a significant decrease in the cumulative presence in IC (−3.3 vs. −0.9, p < 0.001; η2 = 0.20) on Day 7 and on Day 14 (−4.2 vs. −2.9, p = 0.027; η2 = 0.08). Discussion/Conclusions: Our findings suggest that CAPeo possesses potent antiviral activity against SARS-CoV-2 in addition tο its effect against influenza A and B and human rhinovirus HRV14 strains. The early and effective impact on alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for patients with mild COVID-19.