bluuebunny/crossref_metadata_2025 huggingface dataset:
Current and Emerging Strategies to Treat Urothelial Carcinoma
Authors: Rani Berkha , Ignatz-Hoover James J. , Rana Priyanka S. , Driscoll James J.
Published: October 2023

Urothelial cell carcinoma (UCC, bladder cancer, BC) remains a difficult-to-treat malignancy with a rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years of age; it is ~four times more commonly observed in men than women. The most important risk factor for developing BC is tobacco smoking, which accounts for ~50% of cases, followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC remains generally incurable and is associated with intrinsic and acquired drug and immune resistance. UCC is lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and a high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss therapies to improve UCC management and how comprehensive tumor profiling can identify actionable biomarkers and eventually fulfill the promise of precision medicine for UCC patients.
Modulation of the Tumor Microenvironment by Ellagic Acid in Rat Model for Hepatocellular Carcinoma: A Potential Target against Hepatic Cancer Stem Cells
Authors: Ramadan Wafaa S. , Alkarim Saleh , Moulay Mohammed , Alrefeai Ghadeer , Alkudsy Fatma , Hakeem Khalid Rehman , Iskander Ashwaq
Published: October 2023

The resistance to therapy and relapse in hepatocellular carcinoma (HCC) is highly attributed to hepatic cancer stem cells (HCSCs). HCSCs are under microenvironment control. This work aimed to assess the systemic effect of ellagic acid (EA) on the HCC microenvironment to decline HCSCs. Fifty Wistar rats were divided into six groups: negative control (CON), groups 2 and 3 for solvents (DMSO), and (OVO). Group 4 was administered EA only. The (HCC-M) group, utilized as an HCC model, administered CCL4 (0.5 mL/kg in OVO) 1:1 v/v, i.p) for 16 weeks. HCC-M rats were treated orally with EA (EA + HCC) 50 mg/kg bw for five weeks. Biochemical, morphological, histopathological, and immunohistochemical studies, and gene analysis using qRT-PCR were applied. Results revealed elevated liver injury biomarkers ALT, AST, ALP, and tumor biomarkers AFP and GGT, and marked nodularity of livers of HCC-M. EA effectively reduced the biomarkers and restored the altered structure of the livers. At the mRNA level, EA downregulated the expression of TGF-α, TGF-β, and VEGF, and restored p53 expression. This induced an increase in apoptotic cells immunostained with caspase3 and decreased the CD44 immunostained HCSCs. EA could modulate the tumor microenvironment in the HCC rat model and ultimately target the HCSCs.
A Narrative Review on CD44’s Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence
Authors: Inoue Akihiro , Ohnishi Takanori , Nishikawa Masahiro , Ohtsuka Yoshihiro , Kusakabe Kosuke , Yano Hajime , Tanaka Junya , Kunieda Takeharu
Published: October 2023

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5–2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5–5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence.
Stress Keratin 17 Is a Predictive Biomarker Inversely Associated with Response to Immune Check-Point Blockade in Head and Neck Squamous Cell Carcinomas and Beyond
Authors: Lozar Taja , Laklouk Israa , Golfinos Athena E. , Gavrielatou Niki , Xu Jin , Flynn Christopher , Keske Aysenur , Yu Menggang , Bruce Justine Y. , Wang Wei , Grasic Kuhar Cvetka , Bailey Howard H. , Harari Paul M. , Dinh Huy Q. , Rimm David L. , Hu Rong , Lambert Paul F. , Fitzpatrick Megan B.
Published: October 2023

Low response rates in immune check-point blockade (ICB)-treated head and neck squamous cell carcinoma (HNSCC) drive a critical need for robust, clinically validated predictive biomarkers. Our group previously showed that stress keratin 17 (CK17) suppresses macrophage-mediated CXCL9/CXCL10 chemokine signaling involved in attracting activated CD8+ T cells into tumors, correlating with decreased response rate to pembrolizumab-based therapy in a pilot cohort of ICB-treated HNSCC (n = 26). Here, we performed an expanded analysis of the predictive value of CK17 in ICB-treated HNSCC according to the REMARK criteria and investigated the gene expression profiles associated with high CK17 expression. Pretreatment samples from pembrolizumab-treated HNSCC patients were stained via immunohistochemistry using a CK17 monoclonal antibody (n = 48) and subjected to spatial transcriptomic profiling (n = 8). Our findings were validated in an independent retrospective cohort (n = 22). CK17 RNA expression in pembrolizumab-treated patients with various cancer types was investigated for predictive significance. Of the 48 patients (60% male, median age of 61.5 years), 21 (44%) were CK17 high, and 27 (56%) were CK17 low. A total of 17 patients (35%, 77% CK17 low) had disease control, while 31 patients (65%, 45% CK17 low) had progressive disease. High CK17 expression was associated with a lack of disease control (p = 0.037), shorter time to treatment failure (p = 0.025), and progression-free survival (PFS, p = 0.004), but not overall survival (OS, p = 0.06). A high CK17 expression was associated with lack of disease control in an independent validation cohort (p = 0.011). PD-L1 expression did not correlate with CK17 expression or clinical outcome. CK17 RNA expression was predictive of PFS and OS in 552 pembrolizumab-treated cancer patients. Our findings indicate that high CK17 expression may predict resistance to ICB in HNSCC patients and beyond.
Role of Nucleobindin-2 in the Clinical Pathogenesis and Treatment Resistance of Glioblastoma
Authors: Lin I-Cheng , Chang Chih-Hui , Chong Yoon Bin , Kuo Shih-Hsun , Cheng Yu-Wen , Lieu Ann-Shung , Tseng Tzu-Ting , Lin Chien-Ju , Tsai Hung-Pei , Kwan Aij-Lie
Published: October 2023

Glioblastoma (GBM) stands as the most prevalent primary malignant brain tumor, typically resulting in a median survival period of approximately thirteen to fifteen months after undergoing surgery, chemotherapy, and radiotherapy. Nucleobindin-2 (NUCB2) is a protein involved in appetite regulation and energy homeostasis. In this study, we assessed the impact of NUCB2 expression on tumor progression and prognosis of GBM. We further evaluated the relationship between NUCB2 expression and the sensitivity to chemotherapy and radiotherapy in GBM cells. Additionally, we compared the survival of mice intracranially implanted with GBM cells. High NUCB2 expression was associated with poor prognosis in patients with GBM. Knockdown of NUCB2 reduced cell viability, migration ability, and invasion ability of GBM cells. Overexpression of NUCB2 resulted in reduced apoptosis following temozolomide treatment and increased levels of DNA damage repair proteins after radiotherapy. Furthermore, mice intracranially implanted with NUCB2 knockdown GBM cells exhibited longer survival compared to the control group. NUCB2 may serve as a prognostic biomarker for poor outcomes in patients with GBM. Additionally, NUCB2 not only contributes to tumor progression but also influences the sensitivity of GBM cells to chemotherapy and radiotherapy. Therefore, targeting NUCB2 protein expression may represent a novel therapeutic approach for the treatment of GBM.
New Applications of Gas Chromatography and Gas Chromatography-Mass Spectrometry for Novel Sample Matrices in the Forensic Sciences: A Literature Review
Authors: Gould Oliver , Nguyen Ngoc , Honeychurch Kevin C.
Published: October 2023

The investigation of novel sample matrices in the forensic sciences offers several possible advantages, such as allowing for results to be obtained in cases where common sample types are absent. This review focuses on the application of gas chromatography and gas chromatography–mass spectrometry (GC-MS) for the determination of drugs in alternative sample matrices, including hair, sweat, meconium, breast milk, and vitreous humour. Less common sample types are also reported including air, cerumen, insects, and their larvae and pupae. The application of pyrolysis GC-MS (Py GC-MS) is also reviewed, showing the possibility of determining high molecular weight drugs which would commonly be unattainable by GC-MS. The application of Py GC-MS for the simulation and investigation of the underlying chemistry and the products formed in the smoking of drugs is also reported.
Synthesis of Quaternary (Ni, Co, Cu)Se2 Nanosheet Arrays on Carbon Cloth for Non-Enzymatic Glucose Determination
Authors: Chen Yuanyuan , Wang Huan , Chen Huinan , Song Jingyao , Deng Dongmei , Luo Liqiang
Published: October 2023

Unlike transition metal oxides and sulfides, transition metal-based selenides display higher electrical conductivity, more electroactive unsaturated edge sites, and better chemical stability, which have found extensive usage in electrocatalysis. In this work, simple hydrothermal and solvothermal procedures were employed to synthesize quaternary (Ni, Co, Cu)Se2 nanosheet arrays on carbon cloth (CC) to measure glucose. The conductivity of the material can be effectively elevated by adding Se element to form selenides, and the synergistic effect between the three selenides can improve the electrocatalytic performance. Consequently, in the ranges of 0.01–600 μM and 600–9000 μM, respectively, the current response of the synthesized material to glucose concentration exhibited linear relationships. The sensor demonstrated excellent sensitivity and a low detection limit of 5.82 nM. Furthermore, the practical applicability of the constructed biosensor was proved by using it to quantify the amount of glucose in human serum.
An Information Security Engineering Framework for Modeling Packet Filtering Firewall Using Neutrosophic Petri Nets
Authors: Madhloom Jamal Khudair , Noori Zainab Hammoodi , Ebis Sif K. , Hassen Oday A. , Darwish Saad M.
Published: October 2023

Due to the Internet’s explosive growth, network security is now a major concern; as a result, tracking network traffic is essential for a variety of uses, including improving system efficiency, fixing bugs in the network, and keeping sensitive data secure. Firewalls are a crucial component of enterprise-wide security architectures because they protect individual networks from intrusion. The efficiency of a firewall can be negatively impacted by issues with its design, configuration, monitoring, and administration. Recent firewall security methods do not have the rigor to manage the vagueness that comes with filtering packets from the exterior. Knowledge representation and reasoning are two areas where fuzzy Petri nets (FPNs) receive extensive usage as a modeling tool. Despite their widespread success, FPNs’ limitations in the security engineering field stem from the fact that it is difficult to represent different kinds of uncertainty. This article details the construction of a novel packet-filtering firewall model that addresses the limitations of current FPN-based filtering methods. The primary contribution is to employ Simplified Neutrosophic Petri nets (SNPNs) as a tool for modeling discrete event systems in the area of firewall packet filtering that are characterized by imprecise knowledge. Because of SNPNs’ symbolic ability, the packet filtration model can be quickly and easily established, examined, enhanced, and maintained. Based on the idea that the ambiguity of a packet’s movement can be described by if–then fuzzy production rules realized by the truth-membership function, the indeterminacy-membership function, and the falsity-membership functional, we adopt the neutrosophic logic for modelling PN transition objects. In addition, we simulate the dynamic behavior of the tracking system in light of the ambiguity inherent in packet filtering by presenting a two-level filtering method to improve the ranking of the filtering rules list. Results from experiments on a local area network back up the efficacy of the proposed method and illustrate how it can increase the firewall’s susceptibility to threats posed by network traffic.
Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy
Authors: Antunac Katarina , Mayer Ljiljana , Banovic Marija , Beketic-Oreskovic Lidija
Published: October 2023

Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab–pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.
Brain Metastases from Breast Cancer Histologically Exhibit Solid Growth Pattern with at Least Focal Comedonecrosis: A Histopathologic Study on a Monocentric Series of 30 Cases
Authors: Farina Jessica , Angelico Giuseppe , Vecchio Giada Maria , Salvatorelli Lucia , Magro Gaetano , Puzzo Lidia , Palicelli Andrea , Zanelli Magda , Altieri Roberto , Certo Francesco , Spadola Saveria , Zizzo Maurizio , Barbagallo Giuseppe Maria Vincenzo , Caltabiano Rosario , Broggi Giuseppe
Published: October 2023

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable of suggesting the mammary origin of a metastatic carcinoma in the brain. The following histological features were collected from a series of 30 cases of brain metastases from breast cancer: (i) a solid growth pattern; (ii) the presence of comedonecrosis; and (iii) glandular differentiation. Our results showed that most cases histologically exhibited a solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility for leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 in the immunohistochemical panel.
The Prognostic Value of Creatine Kinase-MB Dynamics after Primary Angioplasty in ST-Elevation Myocardial Infarctions
Authors: Popa Delia Melania , Macovei Liviu , Moscalu Mihaela , Sascău Radu Andy , Stătescu Cristian
Published: October 2023

Background: In STEMIs, the evaluation of the relationship between biomarkers of myocardial injury and patients’ prognoses has not been completely explored. Increased levels of CK-MB in patients with a STEMI undergoing primary angioplasty are known to be associated with higher mortality rates, yet the correlation of these values with short-term evolution remains unknown. Material and Methods: The research encompassed a sample of 80 patients diagnosed with STEMIs, and its methodology entailed a retrospective analysis of the data collected during their hospital stays. The study population was then categorized into three distinct analysis groups based on the occurrence or absence of acute complications and fatalities. Results: The findings indicated that there is a notable correlation between rising levels of CK-MB upon admission and peak CK-MB levels with a reduction in left ventricular ejection fraction. Moreover, the CK-MB variation established a point of reference for anticipating complications at 388 U/L, and a cut-off value for predicting death at 354 U/L. Conclusion: CK-MB values are reliable indicators of the progress of patients with STEMIs. Furthermore, the difference between the peak and admission CK-MB levels demonstrates a high accuracy of predicting complications and has a significant predictive power to estimate mortality risk.
Gender Differences and Amputation Risk in Peripheral Artery Disease—A Single-Center Experience
Authors: Onofrei Viviana , Adam Cristina Andreea , Marcu Dragos Traian Marius , Leon Maria-Magdalena , Cumpăt Carmen , Mitu Florin , Cojocaru Doina-Clementina
Published: October 2023

Background and Objectives: Peripheral artery disease (PAD) affects both genders, but the knowledge of clinical and therapeutic aspects particular to each gender has a prognostic value, modulating the risk of amputation and helping to reduce the risk of death or the occurrence of an acute vascular event secondary to optimal management. Materials and Methods: We conducted a retrospective, descriptive study that included 652 patients with PAD who were evaluated at “St. Spiridon” Hospital’s Cardiology Department and divided into two groups according to gender: women (100 cases) and men (552 cases). We evaluated demographics, anthropometric data, as well as clinical and paraclinical parameters in the two groups. Results: Men had a lower mean age (p < 0.001), higher mean BMI (p = 0.049) and were more frequent smokers. (p = 0.008). Hypercholesterolemia (p = 0.026), obesity (p = 0.009), concomitant cerebrovascular (p = 0.005) and chronic kidney disease (p = 0.046) were more common in women, while coronary artery disease (p = 0.033) was more common in men. The number of angiographic stenotic lesions (p = 0.037) is a statistically significant parameter in our study, with both genders predominantly associated with stenotic lesions. In addition, directly proportional relationships were found between smoking, uric acid, inflammatory markers, and the number of stenotic lesions and thromboses or the ankle–brachial index (ABI). In the subgroup of men, the number of stenotic and thrombosed lesions positively correlated with the ABI value (p < 0.001). The presence of more than three cardiovascular risk factors (p = 0.001) and serum triglyceride levels (p = 0.019) significantly correlated with the number of angiographically detected lesions. We applied several risk scores (PREVENT III, Finnvasc Score, or GermanVasc risk score) in our study group for prognostic purposes, without showing statistically significant differences between genders. Men, rest pain, gangrene, smoking status, the presence of more than three cardiovascular risk factors, or a serum HDL-cholesterol level below 40 mg/dL (p < 0.001 for all parameters) are independent predictors associated with amputation in our study group. Conclusions: In our study, we demonstrated that several clinical–paraclinical particularities guide the diagnosis, providing the clinician with prognostic and therapeutic tools to choose the optimal management with maximum benefits.
Improved [18F]FDG PET/CT Diagnostic Accuracy for Infective Endocarditis Using Conventional Cardiac Gating or Combined Cardiac and Respiratory Motion Correction (CardioFreezeTM)
Authors: ten Hove D. , Sinha B. , van Snick J. H. , Slart R. H. J. A. , Glaudemans A. W. J. M.
Published: October 2023

Infective endocarditis (IE) is a serious and diagnostically challenging condition. [18F]FDG PET/CT is valuable for evaluating suspected IE, but it is susceptible to motion-related artefacts. This study investigated the potential benefits of cardiac motion correction for [18F]FDG PET/CT. In this prospective study, patients underwent [18F]FDG PET/CT for suspected IE, combined with a conventional cardiac gating sequence, a data-driven cardiac and respiratory gating sequence (CardioFreezeTM), or both. Scans were performed in adherence to EANM guidelines and assessors were blinded to patients’ clinical contexts. Final diagnosis of IE was established based on multidisciplinary consensus after a minimum of 4 months follow-up and surgical findings, whenever performed. Seven patients participated in the study, undergoing both an ungated [18F] FDG-PET/CT and a scan with either conventional cardiac gating, CardioFreezeTM, or both. Cardiac motion correction improved the interpretability of [18F]FDG PET/CT in four out of five patients with valvular IE lesions, regardless of the method of motion correction used, which was statistically significant by Wilcoxon’s signed rank test: p = 0.046. In one patient the motion-corrected sequence confirmed the diagnosis of endocarditis, which had been missed on non-gated PET. The performance of the two gating sequences was comparable. In conclusion, in this exploratory study, cardiac motion correction of [18F]FDG PET/CT improved the interpretability of [18F]FDG PET/CT. This may improve the sensitivity of PET/CT for suspected IE. Further larger comparative studies are necessary to confirm the additive value of these cardiac motion correction methods.
Skin Lesion Classification and Detection Using Machine Learning Techniques: A Systematic Review
Authors: Debelee Taye Girma
Published: October 2023

Skin lesions are essential for the early detection and management of a number of dermatological disorders. Learning-based methods for skin lesion analysis have drawn much attention lately because of improvements in computer vision and machine learning techniques. A review of the most-recent methods for skin lesion classification, segmentation, and detection is presented in this survey paper. The significance of skin lesion analysis in healthcare and the difficulties of physical inspection are discussed in this survey paper. The review of state-of-the-art papers targeting skin lesion classification is then covered in depth with the goal of correctly identifying the type of skin lesion from dermoscopic, macroscopic, and other lesion image formats. The contribution and limitations of various techniques used in the selected study papers, including deep learning architectures and conventional machine learning methods, are examined. The survey then looks into study papers focused on skin lesion segmentation and detection techniques that aimed to identify the precise borders of skin lesions and classify them accordingly. These techniques make it easier to conduct subsequent analyses and allow for precise measurements and quantitative evaluations. The survey paper discusses well-known segmentation algorithms, including deep-learning-based, graph-based, and region-based ones. The difficulties, datasets, and evaluation metrics particular to skin lesion segmentation are also discussed. Throughout the survey, notable datasets, benchmark challenges, and evaluation metrics relevant to skin lesion analysis are highlighted, providing a comprehensive overview of the field. The paper concludes with a summary of the major trends, challenges, and potential future directions in skin lesion classification, segmentation, and detection, aiming to inspire further advancements in this critical domain of dermatological research.
Acute Hemorrhagic Encephalomyelitis in the Context of MOG Antibody-Associated Disease. Comment on Chen et al. Rapid Progressive Fatal Acute Hemorrhagic Encephalomyelitis. Diagnostics 2023, 13, 2481
Authors: Kim Sohyeon , Eun Mi-Yeon , Lee Jae-Joon , Seok Hung Youl
Published: October 2023

The study by Chen et al. of a 56-year-old man diagnosed with acute hemorrhagic encephalomyelitis (AHEM) had a significant impact on us. The authors provided a comprehensive account of their diagnostic journey and emphasized the need to differentiate myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from AHEM. However, recent research suggests that AHEM may not be an isolated entity, but rather a phenotype within MOGAD. The patient’s clinical presentation included MRI brain lesions characteristic of MOGAD in addition to hemorrhagic abnormalities. These findings raise the possibility that AHEM in this case represents a MOGAD phenotype. In conclusion, it is important to recognize the potential association between AHEM and MOGAD, especially when distinct MOGAD brain MRI patterns are present, as in this case.
Primary Cutaneous Cryptococcosis in an Immunocompetent Patient: Diagnostic Workflow and Choice of Treatment
Authors: Panza Francesca , Montagnani Francesca , Baldino Gennaro , Custoza Cosimo , Tumbarello Mario , Fabbiani Massimiliano
Published: October 2023

Cryptococcosis is an opportunistic infection in immunocompromised patients, involving mainly the lungs and central nervous system; however, the skin, eyes and genitourinary tract could also be involved as secondary sites of infection. Primary cutaneous cryptococcosis (PCC) is a distinct clinical entity that can occur in both immunocompetent and -compromised patients, usually trough skin injury. In immunocompetent patients, it is a very rare infection, presenting with non-specific clinical pictures and being challenging to diagnose. Herein, we present the case of an immunocompetent man with PCC due to Cryptococcus neoformans on his right forearm. PCC was diagnosed by a histological and cultural examination. Causes of concomitant immunosuppression were ruled out. A secondary cutaneous cryptococcosis was excluded with careful investigations. Therapy with oral fluconazole for three months was successfully performed, without evidence of recurrence in the following six months. Complete clinical recovery was achieved after three months of oral antifungal therapy, suggesting that longer courses of treatment could be avoided when faced with PCC in immunocompetent patients.
Evaluating Deep Q-Learning Algorithms for Controlling Blood Glucose in In Silico Type 1 Diabetes
Authors: Tejedor Miguel , Hjerde Sigurd Nordtveit , Myhre Jonas Nordhaug , Godtliebsen Fred
Published: October 2023

Patients with type 1 diabetes must continually decide how much insulin to inject before each meal to maintain blood glucose levels within a healthy range. Recent research has worked on a solution for this burden, showing the potential of reinforcement learning as an emerging approach for the task of controlling blood glucose levels. In this paper, we test and evaluate several deep Q-learning algorithms for automated and personalized blood glucose regulation in an in silico type 1 diabetes patient with the goal of estimating and delivering proper insulin doses. The proposed algorithms are model-free approaches with no prior information about the patient. We used the Hovorka model with meal variation and carbohydrate counting errors to simulate the patient included in this work. Our experiments compare different deep Q-learning extensions showing promising results controlling blood glucose levels, with some of the proposed algorithms outperforming standard baseline treatment.
Interpretation of Heart and Lungs Sounds Acquired via Remote, Digital Auscultation Reached Fair-to-Substantial Levels of Consensus among Specialist Physicians
Authors: Magor Diana , Berkov Evgeny , Siomin Dmitry , Karniel Eli , Lasman Nir , Waldman Liat Radinsky , Gringauz Irina , Stern Shai , Kassif Reut Lerner , Barkai Galia , Lewy Hadas , Segal Gad
Published: October 2023

Background. Technological advancement may bridge gaps between long-practiced medical competencies and modern technologies. Such a domain is the application of digital stethoscopes used for physical examination in telemedicine. This study aimed to validate the level of consensus among physicians regarding the interpretation of remote, digital auscultation of heart and lung sounds. Methods. Seven specialist physicians considered both the technical quality and clinical interpretation of auscultation findings of pre-recorded heart and lung sounds of patients hospitalized in their homes. TytoCareTM system was used as a remote, digital stethoscope. Results. In total, 140 sounds (70 heart and 70 lungs) were presented to seven specialists. The level of agreement was measured using Fleiss’ Kappa (FK) variable. Agreement relating to heart sounds reached low-to-moderate consensus: the overall technical quality (FK = 0.199), rhythm regularity (FK = 0.328), presence of murmurs (FK = 0.469), appreciation of sounds as remote (FK = 0.011), and an overall diagnosis as normal or pathologic (FK = 0.304). The interpretation of some of the lung sounds reached a higher consensus: the overall technical quality (FK = 0.169), crepitus (FK = 0.514), wheezing (FK = 0.704), bronchial sounds (FK = 0.034), and an overall diagnosis as normal or pathological (FK = 0.386). Most Fleiss’ Kappa values were in the range of “fare consensus”, while in the domains of diagnosing lung crepitus and wheezing, the values increased to the “substantial” level. Conclusions. Bio signals, as recorded auscultations of the heart and lung sounds serving the process of clinical assessment of remotely situated patients, do not achieve a high enough level of agreement between specialized physicians. These findings should serve as a catalyzer for improving the process of telemedicine-attained bio-signals and their clinical interpretation.
Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms at “Challenging Sites” Using a Double-Balloon Endoluminal Interventional Platform: A Single-Center Study
Authors: Andrisani Gianluca , Di Matteo Francesco Maria
Published: October 2023

Background: Colonic endoscopic submucosal dissection (ESD) at “challenging sites” such as the cecum, ascending colon, and colonic flexures could be difficult even for expert endoscopists due to poor endoscope stability/maneuverability, steep angles, and thinner wall thickness. A double-balloon endoluminal intervention platform (EIP) has been introduced in the market to fasten and facilitate ESD, particularly when located at difficult sites. Here, we report our initial experience with an EIP comparing the outcomes of an EIP versus standard ESD (S-ESD) at “challenging sites”. Materials and methods: We retrospectively collected data on consecutive patients with colonic lesions located in the right colon and at flexures who underwent ESD in our tertiary referral center between March 2019 and May 2023. Endoscopic and clinical outcomes (technical success, en bloc resection rate, R0 resection rate, procedure time, time to reach the lesion, and adverse events) and 6-month follow-up outcomes were analyzed. Results: Overall, 139 consecutive patients with lesions located at these challenging sites were enrolled (EIP: 31 and S-ESD: 108). Demographic characteristics did not differ between groups. En bloc resection was achieved in 92.3% and 93.5% of patients, respectively, in the EIP and S-ESD groups. Both groups showed a comparable R0 resection rate (EIP vs. S-ESD: 92.3% vs. 97.2%). In patients undergoing EIP-assisted ESD, the total procedure time was shorter (96.1 [30.6] vs. 113.6 [42.3] minutes, p = 0.01), and the mean size of the resected lesions was smaller (46.2 ± 12.7 vs. 55.7 ± 17.6 mm, p = 0.003). The time to reach the lesion was significantly shorter in the EIP group (1.9 ± 0.3 vs. 8.2 ± 2.7 min, p ≤ 0.01). Procedure speed was comparable between groups (14.9 vs. 16.6 mm2/min, p = 0.29). Lower adverse events were observed in the EIP patients (3.8 vs. 10.2%, p = 0.31). Conclusions: EIP allows results that do not differ from S-ESD in the resection of colorectal superficial neoplasms localized in “challenging sites” in terms of efficacy and safety. EIP reduces the time to reach the lesions and may more safely facilitate endoscopic resection.
Predicting the Probability of the Incidence of Maxillary Sinus Fungus Ball in Patients Using Nomogram Models
Authors: Fan Yu-Hsi , Shih Kai-Yi , Wu Pei-Wen , Huang Yen-Lin , Lee Ta-Jen , Huang Chi-Che , Chang Po-Hung , Huang Chien-Chia
Published: October 2023

Maxillary sinus fungal ball (MSFB) is the most common type of non-invasive fungal rhinosinusitis. Since MSFB requires a unique treatment strategy and is associated with potentially severe complications, timely and precise diagnosis is crucial. Computed tomography (CT) is the first-line imaging tool for evaluating chronic rhinosinusitis. Accordingly, we aimed to investigate the clinical and CT imaging characteristics of MSFB. We retrospectively enrolled 97 patients with unilateral MSFB and 158 with unilateral non-fungal maxillary rhinosinusitis. The clinical characteristics, laboratory data, and CT imaging features of participants were evaluated. Older age, female sex, lower white blood cell and neutrophil counts, and CT imaging features (including an irregular surface, erosion of the medial sinus wall, sclerosis of the lateral sinus wall, and intralesional hyperdensity) were significantly associated with MSFB. The presence of adjacent maxillary odontogenic pathology was associated with a decreased likelihood of the incidence of MSFB in unilateral maxillary rhinosinusitis. Separate nomograms were created for patients, without and with the use of CT scan, to predict the probabilities of MSFB in patients with unilateral maxillary rhinosinusitis. We proposed two nomograms based on the clinical and CT characteristics of patients with MSFB. These could serve as evaluation tools to assist clinicians in determining the need for undergoing CT and facilitate the accurate and timely diagnosis of MSFB.
DermAI 1.0: A Robust, Generalized, and Novel Attention-Enabled Ensemble-Based Transfer Learning Paradigm for Multiclass Classification of Skin Lesion Images
Authors: Sanga Prabhav , Singh Jaskaran , Dubey Arun Kumar , Khanna Narendra N. , Laird John R. , Faa Gavino , Singh Inder M. , Tsoulfas Georgios , Kalra Mannudeep K. , Teji Jagjit S. , Al-Maini Mustafa , Rathore Vijay , Agarwal Vikas , Ahluwalia Puneet , Fouda Mostafa M. , Saba Luca , Suri Jasjit S.
Published: October 2023

Skin lesion classification plays a crucial role in dermatology, aiding in the early detection, diagnosis, and management of life-threatening malignant lesions. However, standalone transfer learning (TL) models failed to deliver optimal performance. In this study, we present an attention-enabled ensemble-based deep learning technique, a powerful, novel, and generalized method for extracting features for the classification of skin lesions. This technique holds significant promise in enhancing diagnostic accuracy by using seven pre-trained TL models for classification. Six ensemble-based DL (EBDL) models were created using stacking, softmax voting, and weighted average techniques. Furthermore, we investigated the attention mechanism as an effective paradigm and created seven attention-enabled transfer learning (aeTL) models before branching out to construct three attention-enabled ensemble-based DL (aeEBDL) models to create a reliable, adaptive, and generalized paradigm. The mean accuracy of the TL models is 95.30%, and the use of an ensemble-based paradigm increased it by 4.22%, to 99.52%. The aeTL models’ performance was superior to the TL models in accuracy by 3.01%, and aeEBDL models outperformed aeTL models by 1.29%. Statistical tests show significant p-value and Kappa coefficient along with a 99.6% reliability index for the aeEBDL models. The approach is highly effective and generalized for the classification of skin lesions.
Sustainable Optimal Control for Switched Pollution-Control Problem with Random Duration
Authors: Wu Yilun , Tur Anna , Wang Hongbo
Published: October 2023

Considering the uncertainty of game duration and periodic seasonal fluctuation, an n-player switched pollution-control differential game is modeled to investigate a sustainable and adaptive strategy for players. Based on the randomness of game duration, two scenarios are considered in this study. In the first case, the game duration is a random variable, Tf, described by the shifted exponential distribution. In the second case, we assumed that players’ equipment is heterogeneous, and the i-th player’s equipment failure time, Tfi, is described according to the shifted exponential distribution. The game continues until a player’s equipment breaks down. Thus, the game duration is defined as Tf=min{Tf1,…,Tfn}. To achieve the goal of sustainable development, an environmentally sustainable strategy and its corresponding condition are defined. By using Pontryagin’s maximum principle, a unique control solution is obtained in the form of a hybrid limit cycle, the state variable converges to a stable hybrid limit cycle, and the total payoff of all players increases and then converges. The results indicate that the environmentally sustainable strategy in the n-player pollution-control cooperative differential game with switches and random duration is a unique strategy that not only ensures profit growth but also considers environmental protection.
Shannon Entropy of Ramsey Graphs with up to Six Vertices
Authors: Frenkel Mark , Shoval Shraga , Bormashenko Edward
Published: October 2023

Shannon entropy quantifying bi-colored Ramsey complete graphs is introduced and calculated for complete graphs containing up to six vertices. Complete graphs in which vertices are connected with two types of links, labeled as α-links and β-links, are considered. Shannon entropy is introduced according to the classical Shannon formula considering the fractions of monochromatic convex α-colored polygons with n α-sides or edges, and the fraction of monochromatic β-colored convex polygons with m β-sides in the given complete graph. The introduced Shannon entropy is insensitive to the exact shape of the polygons, but it is sensitive to the distribution of monochromatic polygons in a given complete graph. The introduced Shannon entropies Sα and Sβ are interpreted as follows: Sα is interpreted as an average uncertainty to find the green α−polygon in the given graph; Sβ is, in turn, an average uncertainty to find the red β−polygon in the same graph. The re-shaping of the Ramsey theorem in terms of the Shannon entropy is suggested. Generalization for multi-colored complete graphs is proposed. Various measures quantifying the Shannon entropy of the entire complete bi-colored graphs are suggested. Physical interpretations of the suggested Shannon entropies are discussed.
Artificial Intelligence (AI) Trust Framework and Maturity Model: Applying an Entropy Lens to Improve Security, Privacy, and Ethical AI
Authors: Mylrea Michael , Robinson Nikki
Published: October 2023

Recent advancements in artificial intelligence (AI) technology have raised concerns about the ethical, moral, and legal safeguards. There is a pressing need to improve metrics for assessing security and privacy of AI systems and to manage AI technology in a more ethical manner. To address these challenges, an AI Trust Framework and Maturity Model is proposed to enhance trust in the design and management of AI systems. Trust in AI involves an agreed-upon understanding between humans and machines about system performance. The framework utilizes an “entropy lens” to root the study in information theory and enhance transparency and trust in “black box” AI systems, which lack ethical guardrails. High entropy in AI systems can decrease human trust, particularly in uncertain and competitive environments. The research draws inspiration from entropy studies to improve trust and performance in autonomous human–machine teams and systems, including interconnected elements in hierarchical systems. Applying this lens to improve trust in AI also highlights new opportunities to optimize performance in teams. Two use cases are described to validate the AI framework’s ability to measure trust in the design and management of AI systems.
A Game Theoretic Approach to Collaboration in Policy Coordination
Authors: Herrera-Medina Eleonora , Riera Font Antoni
Published: October 2023

Public policies are courses of action by a government in response to public problems in the real world with the aim of meeting the needs of society. Such policies must be coordinated to avoid inefficiencies. Most attempts to model public policy coordination are qualitative and, therefore, do not yield precise conclusions. More accurate modelling attempts are found in game theory, but they are not entirely appropriate as models of policy coordination, because policy coordination involves a high degree of collaboration. There is only one game-theoretic model of collaboration, and it does not model public policy coordination. The aim of this article is to show that a collaboration-based game theory model is not only feasible, but also more realistic than current game theory models of policy coordination. This was performed by adapting Newton’s seminal model to a society capable of formulating and coordinating policies. When this adapted game was compared to alternative games used to explain policy coordination, it was found that the adapted game made more realistic assumptions, the modelling process was simpler, and it can be applied to a broader range of contexts. By demonstrating that the adapted model offers a feasible theoretical foundation for the modelling of policy coordination, this paper provides a starting point for future modelling efforts in this area.
Augmented Reality in the Science Classroom—Implementing Pre-Service Teacher Training in the Competency Area of Simulation and Modeling According to the DiKoLAN Framework
Authors: Krug Manuel , Thoms Lars-Jochen , Huwer Johannes
Published: October 2023

The digitalization of everyday school life has gained increasing importance for teachers in recent years. In Germany, this is especially true since the publication of the strategy on “Education in the Digital World” by the Standing Conference of the Ministers of Education and Cultural Affairs of the Länder in 2016, which calls for the acquisition of digital competencies by students. In this regard, it is of great importance that future teachers acquire important skills in the field of digitalization during their teacher training in order to effectively and pedagogically use digital media in instruction. In this paper, we present the concept of an intervention on the topic of “Simulation and Modeling” from the competency framework DiKoLAN, which provides possible guidance in relation to the question “which competencies in the field of digitalization should be taught during teacher training?” One focus of the presented concept is the technology of “Augmented Reality,” which has already been described as an effective teaching and learning tool. Furthermore, evaluation results of the seminar are presented, which examine both the effectiveness in terms of conveying the desired competencies through the measurement of self-efficacy expectations, and the attitudes of the pre-service teachers towards the use of AR in science education. The evaluation of the intervention measure shows a significant increase in pre-service teachers’ self-efficacy expectations across all areas of competencies to be taught, as well as a significantly more positive attitude towards the use of AR in science teaching.
Israeli Students’ Evaluations Regarding Leadership Education in Post-Primary Schools
Authors: Perets Shenhav , Davidovitch Nitza , Lewin Eyal
Published: October 2023

This article examines the way students attending middle and high schools in Israel evaluate leadership education in their schools and the extent to which it contributes to their leader self-efficacy. Based on 376 questionnaires completed by teenage girls (n = 243) and boys (n = 133) who attend middle and high school in the public education system in Israel, it focuses on their perceptions regarding their school as their main leadership development establishment. Using a Likert scale to measure attitudes and perceptions of youth leadership, the questionnaire was used to investigate the following topics: the school’s efforts to impart leadership and encourage leadership and leadership ability, their self-perceptions of leadership ability, and the impact of the school staff on their leadership development. Students expressed discontent with the school’s ability to impart and motivate leadership, and family members and youth organizations are perceived as more influential. Students in middle schools participate more in leadership programs but evaluate the school’s contribution to leadership development less favorably than high school students. Although girls and boys are participating in leadership programs at a similar rate, girls’ leader self-efficacy is relatively low. Implementing leadership education has some deficiencies that require policymakers to make necessary adjustments regarding age and gender.